The Landmark Series: Scoring Systems for Primary Peritoneal Surface Malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represents an innovative approach to treat or prevent peritoneal metastasis. However, given the morbidity that can be associated with this procedure, adequate patient selection facilitated by scoring systems for primary peritoneal surface malignancy (PSM) is paramount to ensure equitable morbidity as well as acceptable survival outcome. METHODS: Seminal studies on scoring systems for PSM that have laid the foundation for adequate patient selection and prognostication are spotlighted. RESULTS: Quantitative prognostic indicators have been defined for patients with PSM that enable the surgeon to make sound clinical judgements as to who may or may not benefit from CRS/HIPEC. These prognostic indicators include the histopathology of the tumor, findings on the preoperative abdominal and pelvic computerized axial tomography, the Peritoneal Cancer Index, completeness of cytoreduction score, and prior surgical score. CONCLUSIONS: Scoring systems for primary peritoneal surface malignancy reviewed in this article highlight the utility of these systems for patient selection for CRS/HIPEC and prognostication.

Prior Surgical Score: An Analysis of the Prognostic Significance of an Initial Nondefinitive Surgical Intervention in Patients With Peritoneal Carcinomatosis of a Colorectal Origin Undergoing Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy.

BACKGROUND: The prior surgical score estimates the extent of previous surgical intervention by quantitating surgical dissection within 9 abdominopelvic regions. OBJECTIVE: Our aim was to analyze the prognostic significance of the prior surgical score in our cohort of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of a colorectal origin. DESIGN: This was a retrospective analysis of a prospectively maintained database for all patients treated for peritoneal carcinomatosis of a colorectal origin. SETTINGS: The prospectively maintained surgical oncology tumor database was analyzed for the study period 1989-2014. PATIENTS: A total of 407 patients diagnosed with peritoneal carcinomatosis of a colorectal origin and treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy were included in this analysis. MAIN OUTCOME MEASURES: The prognostic significance and clinicopathologic factors associated with an initial nondefinitive surgical intervention in patients with peritoneal carcinomatosis of a colorectal origin undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy was evaluated. RESULTS: There were 210 men (51.6%) and 197 women (48.4%) in the study. Mean age at presentation was 53.7 years (range, 19.0-87.0 y). Data on prior surgical score for 69 patients were missing, leaving us with a study cohort of 338 patients. Grouped by prior surgical score, 46 (13.6%) had a prior surgical score of 0 versus 25 (7.4%), 122 (36.1%), and 145 (42.9%) who had a prior surgical score of 1, 2, or 3. Overall survival was 53.0%. Three- and 5-year survival rates were 75% and 75% for group prior surgical score 0 versus 26% and 13%, 39% and 37%, and 21% and 16% for group prior surgical scores 1, 2, and 3. Median survival time for the various prior surgical score groups were 180.0, 30.4, 30.5, and 21.3 months for prior surgical scores 0, 1, 2, and 3 (p = 0.000). A total of 87.2% of the prior surgical score 0 group had a completeness of cytoreduction score of 0/1 (no residual disease/tumor <0.25 cm) versus 68.0%, 68.1%, and 48.6% for prior surgical scores of 1, 2, or 3 (p = 0.000). Significant independent predictors of a shorter survival in multivariate analysis included a high cytoreduction score status (p < 0.000) and a high prior surgical score (p = 0.05). LIMITATIONS: This study was limited by its retrospective, population-based design. CONCLUSIONS: The extent of a previous nondefinitive surgical intervention contributes to the poor prognosis associated with peritoneal carcinomatosis of a colorectal origin. Independent predictors for an improved overall survival include completeness of cytoreduction and low prior surgical score. See Video Abstract at http://links.lww.com/DCR/A573.

A Prognostic Model for Predicting Overall Survival in Patients with Peritoneal Surface Malignancy of an Appendiceal Origin Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Our aim was to develop a prognostic model for predicting overall survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal adenocarcinoma and peritoneal metastasis. METHODS: A retrospective analysis of a prospectively maintained database for all patients treated for appendiceal adenocarcinoma with peritoneal metastasis from 1989 to 2012 was conducted. RESULTS: Overall, 734 (50.7%) males and 715 (49.3%) females, with a mean age at presentation of 48.6 years, were included. Prognostic variables identified in a univariate Cox analysis included sex, tumor recurrence, tumor histology, Peritoneal Carcinomatosis Index, age at diagnosis, lesion size, completeness of cytoreduction (CC) score, distant metastasis, lymph node status, and use of HIPEC. A multivariate Cox analysis identified distant metastasis, CC score, tumor histology, HIPEC use, and sex as independently predictive of survival. A prognostic index was derived and four risk groups were categorized (≤1, 2-4, 5-10, and ≥10). Median survival for the four risk groups differed significantly: 240 months for patients with a prognostic score ≤1 versus 235, 78.4, and 19.4 months for the cohort of patients with a prognostic score of 2-4, 5-10 and ≥10, respectively (p = 0.000). An internal validation of our prognostic model was carried out on a series of 379 randomly selected patients from our data, which provided corresponding estimates. CONCLUSIONS: Our prognostic model demonstrated a significant difference in overall survival for patients stratified by our derived prognostic scores. External validation of this model in other cohorts of patients is needed.

Management for Peritoneal Metastasis of Colonic Origin: Role of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy: A Single Institution's Experience During Two Decades.

BACKGROUND: Peritoneal metastasis of colonic origin is associated with a poor prognosis. This study aimed to analyze the clinicopathologic characteristics and prognostic predictors of survival in a cohort of patients treated with cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (POIC) during two decades. METHODS: A retrospective study analyzed a prospectively maintained database for all patients treated for peritoneal metastasis of a colonic origin (PCC) from January 1990 to April 2015. RESULTS: The 318 patients in our study comprised 171 men (53.8%) and 147 women (46.2%). The mean age of the patients at presentation was 50.6 years, (range 18-86 years). Overall survival was 42.5%, median survival and follow-up time was 21.5 and 15.0 months respectively. The 3 and 5 years survival rates were respectively 35 and 25%. The median survival time was 20.6 months for the men and 23.1 months for the women (p = 0.14). The mean intraoperative peritoneal carcinomatosis index (PCI) was 15.2. The patients who had a completeness of cytoreduction (CC) score of 0 or 1 (no residual disease <0.25 mm) had a median survival time of 36.6 months compared with 18.3 months for the patients with a CC-2 score and 7.6 months for the patients with a CC-3 score (p < 0.000). The significant independent predictors of survival in the multivariate analysis were the CC score and elevated tumor makers CA153 and CA125. CONCLUSION: For patients with a limited extent of peritoneal metastases, CC is the most important prognostic variable for improved survival of colon cancer patients with peritoneal metastases.

Adverse Events Postoperatively Had No Impact on Long-Term Survival of Patients Treated with Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy for Appendiceal Cancer with Peritoneal Metastases.

BACKGROUND: Appendiceal cancer most commonly metastasizes to the peritoneum. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is the standard of care for appendiceal cancer with peritoneal metastases. Adverse events postoperatively have been associated with reduced survival. We analyzed clinical outcomes, including complications after CRS and HIPEC in patients with appendiceal cancer, in a recent cohort of patients to identify prognostic factors. METHODS: Patients undergoing CRS with HIPEC for appendix cancer with peritoneal metastases between January 2007 and December 2009 were identified. Prospectively collected data were analyzed, including preoperative, intraoperative, and postoperative variables, and multivariate Cox regression models were developed to identify factors independently predicting overall survival (OS). RESULTS: A total of 133 consecutive patients with a median age of 51 years were analyzed; 53.4 % were female. Pre-, intra-, and postoperative clinical variables analyzed for their impact on survival included sex, age, prior surgical score, Peritoneal Cancer Index, completeness of cytoreduction score, histology, lymph node metastases, operative time, blood transfusion, fresh frozen plasma transfusion, perioperative chemotherapy, postoperative complications, length of hospitalization, and disease recurrence. OS at 5 years was 74.4 %, and 5-year recurrence-free survival (RFS) of patients with a complete cytoreduction (CC ≤ 1) was 65.5 %. Factors independently predicting shorter survival included peritoneal mucinous adenocarcinoma (PMCA) histology (hazard ratio [HR] 15.2, 95 % confidence interval [CI] 3.38-69.0), lymph node metastasis (HR 3.82, 95 % CI 1.13-12.8), and incomplete cytoreduction [CC3; HR 13.7, 95 % CI 3.18-59.1). An incomplete cytoreduction was associated with the PMCA variant (p < 0.001). Postoperative complications grade I/II (p = 0.113) and grade III/IV (p = 0.669) had no impact on OS in multivariate analysis. CONCLUSION: CRS with HIPEC can achieve long-term survival for patients with appendix cancer with peritoneal metastases. Histologic subtype, lymph node metastasis, and incomplete cytoreduction are the significant predictors of OS. Postoperative adverse events had no impact on survival.

Cytoreductive Surgery and HIPEC as a Treatment Option for Laparoscopic Resection of Uterine Leiomyosarcoma with Morcellation: Early Results.

BACKGROUND: A new and frequently utilized treatment option for symptomatic uterine leiomyoma is laparoscopic resection with morcellation so the specimen can be extracted through a small abdominal incision or through the vagina. Some of these tumors (approximately 0.2 %) have malignant foci of uterine leiomyosarcoma (ULMS) that is widely disseminated in the process of resection. These patients are in need of effective additional treatments. METHODS: Patients with ULMS were treated with a standardized cytoreductive surgery (CRS), hyperthermic perioperative chemotherapy (HIPEC), and early postoperative intraperitoneal chemotherapy (EPIC) specifically designed for sarcomatosis. Distribution of disease by Peritoneal Cancer Index was recorded by preoperative computed tomography or magnetic resonance imaging and at the time of CRS. Completeness of cytoreduction score was determined after completion of CRS. Morbidity and mortality, as well as interval to start systemic chemotherapy, were prospectively recorded. RESULTS: Six patients with disseminated ULMS after morcellation or slicing underwent CRS and HIPEC plus EPIC. All six patients had complete visible clearing of sarcoma prior to perioperative chemotherapy. Early intervention after morcellation was associated with a lesser extent of disease. No serious morbidity or mortality was observed in early referral patients, and patients eligible for systemic chemotherapy were treated with perioperative chemotherapy within 6 weeks of the CRS. CONCLUSIONS: The future use of laparoscopic resection of ULMS with morcellation is currently under debate. However, patients after laparoscopic resection and morcellation have CRS and HIPEC plus EPIC as a treatment option. Results regarding short-term benefit are suggested by these early data, especially with early referral.

Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive disease for which cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used with remarkable survival benefits. Our aim was to analyze the clinicopathologic characteristics and prognosis of recurrent DMPM managed with iterative CRS and HIPEC. METHODS: A retrospective analysis of a prospectively maintained database for all patients treated for DMPM from 1989 to 2012. RESULTS: Of 205 consecutive CRS and HIPEC procedures, 44 (21.5 %) patients underwent an iterative procedure-22 (50.0 %) males versus 22 (50.0 %) females. Mean age at recurrence was 51.5 years. There was no 30-day mortality following an iterative procedure, and the grade III-V morbidity was 2.3 %. The median overall survival of patients undergoing an iterative CRS and HIPEC was 54 months versus 77 months following an initial CRS and HIPEC (p = 0.96). Patients undergoing an iterative surgery had a 3- and 5-year survival of 61 and 46 %, respectively, versus 60 and 52 % following an initial CRS and HIPEC. Amongst the iterative group, the achieved complete cytoreduction (CC) score was 15.9, 18.2, 22.7, and 43.2 % for CC0, CC1, CC2 and CC3, respectively, versus 3.1, 43.5, 28.6 and 24.8 %, respectively, following initial CRS (p = 0.000). Significant predictors of an improved survival in multivariate analysis were an epithelioid subtype, female sex, complete or near CC (CC0 or CC1), HIPEC regimen utilized, absence of postoperative complication, and age at diagnosis. CONCLUSION: Iterative CRS and HIPEC can be performed safely and appear to have benefits with this group of patients showing an improved median survival.

Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality.

BACKGROUND: Cytoreductive surgery (CRS)/Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is associated with prolonged survival in selected patients with peritoneal surface disease. Yet, for elderly patients (older than 70 years of age) CRS/HIPEC is controversial, due to associated morbidity. METHODS: A retrospective analysis of a prospective database of 950 procedures was performed. Type of malignancy, demographics, performance and resection status, hospitalization, morbidity, mortality, and survival were reviewed. RESULTS: A total of 81 patients (median age 73, range 70-87) underwent CRS/HIPEC between 1991 and 2011. Median follow-up was 48.1 months. Complete cytoreduction was achieved in 44 %. Median survival was 31.8 months for appendiceal cancer, 41.5 for mesothelioma, 54.0 for ovarian cancer, 13.2 for colon cancer, and 7.6 for gastric cancer. The 30-day mortality was 13.6 %. The combined grade III and IV morbidity was 38 %. Median ICU and hospital stay for uncomplicated patients was 1 and 8 days, respectively. The 3-month mortality was 27.4 %. There were no deaths in the octogenarian group. In stepwise multivariate analysis, type of primary (p = 0.03), albumin (p = 0.02), and R status (p = 0.007) were predictive of survival only in the absence of complications. Splitting the data at the midpoint of surgical experience, there was a drop in 1- and 3-month mortality over time to 9.5 and 19.3 %, respectively, while the median survival increased from 11.2 (N = 39) to 46.9 months (N = 42). CONCLUSIONS: HIPEC in the elderly is associated with a steep learning curve and considerable morbidity and mortality. However, age alone is not a contraindication for the procedure. Institutional experience and stringent patient selection are key factors for prolonged survival.

Predicting postoperative morbidity following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) with preoperative FACT-C (Functional Assessment of Cancer Therapy) and patient-rated performance status.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) is associated with significant perioperative morbidity. One goal of our ongoing patient-reported health-related quality of life (HRQoL) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC. METHODS: A retrospective analysis of a prospectively collected clinical database for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done. Patients completed the Functional Assessment of Cancer Therapy questionnaire plus the colon symptom subscale, in addition to the Eastern Cooperative Oncology Group (ECOG) performance status rating prior to CS+HIPEC. The trial outcome index (TOI), a specific measure of function, symptoms, and physical well being of the patient, was analyzed. The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C. RESULTS: Of 855 patients, 387 (45.2 %) participated in the HRQoL trials. Mean age was 53.3 years, and 213 (55 %) were female versus 174 (45 %) males. There were 240 patients (62 %) who had a complication versus 147 (38 %) who had no complication. A 30-day mortality rate of 7.7 % (30) was documented. Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7; P < 0.001. Independent predictors of 30-day mortality on multivariate analysis included TOI (0.05), age (0.001), and smoking (0.001). Patients with a higher TOI score were less likely to suffer a mortality (95 % CI 0.9-1.0, P = 0.05). Patients with a higher emotional well being (EWB) score were less likely to suffer a complication 0.9 (95 % CI 0.87-1.0, P = 0.04). Other independent predictors of postoperative morbidity included diabetic status (P = 0.05), ECOG performance status (0.001), and gender (0.02). CONCLUSIONS: Preoperative HRQoL, as measured by FACT-C and ECOG performance status and added to traditional factors, helps predict postoperative morbidity and mortality following CS+HIPEC.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from rectal cancer.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment most likely to achieve prolonged survival in peritoneal carcinomatosis (PC). Yet the efficacy of HIPEC in rectal patients is controversial because of the retroperitoneal location of the primary tumor. Therefore, we reviewed our experience in patients with PC from a rectal primary tumor. METHODS: A retrospective analysis of a prospective database of 950 HIPEC procedures was performed. Performance status, age, albumin level, prior surgical score, resection status, morbidity, mortality, and survival were reviewed. RESULTS: A total of 13 and 204 patients with PC from rectal and colon cancer, respectively, were identified. Median follow-up was 40.1 and 88.1 months, respectively. Eastern Cooperative Oncology Group (ECOG) score was zero or one for 92 % of patients with rectal cancer and 83 % for colon, while R1 resection was achieved in 54 and 51 %. The 30-day mortality was 5 % for colon cancer. There were no deaths in the rectal group. The morbidity for the colon and rectal groups was 57 and 46 %, respectively, with a 23 % 30-day readmission rate. In univariate analysis, age, ECOG, prior surgical score, albumin level, and node and resection status were not statistically significant in predicting survival for the rectal cancer patients. Median survival for the rectal and colon groups was 14.6 versus 17.3 months, while the 3-year survival was 28.2 versus 25.1 %. CONCLUSIONS: Our data demonstrate similar 3-year survival for patients with rectal and colon cancer PC treated with CS/HIPEC. This can be attributed to patient selection bias. Selected rectal cancer PC patients should not be excluded from an attempted cytoreduction and HIPEC.

A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C.

BACKGROUND: Although peritoneal carcinomatosis (PC) from colorectal and appendiceal tumors is consistent with metastatic disease, complete cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) using mitomycin C (MMC) can improve survival. A recent phase I study by our group using hyperthermic intraperitoneal oxaliplatin has demonstrated its safety and appropriate dose. Our goal in this study is to present a single institution's experience with the hematologic toxicities of the two agents. METHODS: We performed a retrospective review of 187 patients with PC of colorectal or appendiceal origin who underwent HIPEC with MMC or oxaliplatin between October 2006 and September 2009. Hematologic toxicities were graded according to the NCI Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: Of the 187 patients, 55 had oxaliplatin-based HIPEC while 132 patients received MMC. Splenectomy was performed in 95 patients (50.8%) due to disease involvement. When comparing hematologic toxicity for MMC and oxaliplatin among the cohort of patients who underwent splenectomy, a statistically significant difference was noted in the incidence of platelet (P = .02) and neutrophil (P = .05) toxicity, with oxaliplatin having a higher incidence of grade 3 and grade 4 platelet and neutrophil toxicity respectively. However, no statistically significant difference in hematologic toxicity was noted between the two agents in patients who did not undergo splenectomy during cytoreductive surgery. CONCLUSIONS: Oxaliplatin-based HIPEC for PC of colorectal and appendiceal origin is associated with similar white blood cell toxicity and higher platelet and neutrophil toxicity compared to MMC-based HIPEC.

Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival of patients with peritoneal surface malignancy. On recurrence, a repeat CRS/HIPEC is a treatment option. STUDY DESIGN: A retrospective analysis of 868 CRS/HIPEC procedures was performed. Type of primary, functional status, completion of resection, hospitalization, morbidity, mortality, and survival were reviewed. RESULTS: Sixty-two patients (7.7%) underwent a second CRS/HIPEC, including 33 patients with appendiceal primaries, 8 ovarian, 7 mesotheliomas, 4 colon cancers, and 10 various malignancies. Median follow-up was 60.8 months. Median overall survival in months was 85.3 for appendiceal cancer, 52.9 for mesothelioma, 60.1 for ovarian, and 137.4 for colon cancer. R1 resection was achieved in 43.5% after both procedures. Median survival after the second cytoreduction was 52.1 months for appendiceal cancer, 21.8 for mesothelioma, 53.9 for ovarian, and 55.7 for colon cancer. Median survival was 55.7 months for R1 resection, 20.3 months for R2a resection, and 15.5 months for R2b-R2c. Median ICU and hospital stay was 1 and 7.5 days, respectively. The 30-day morbidity after the second CRS/HIPEC was 48.4% and mortality was 3.2%. In multivariate analysis, the R status of the second CRS/HIPEC (p = 0.013) and the interval between the 2 procedures (p = 0.009) were significant in predicting improved survival. CONCLUSIONS: In experienced tertiary centers and for selected patients, a repeat CRS/HIPEC procedure has morbidity and mortality similar to the initial cytoreduction. Survival depends primarily on the completion of the repeat cytoreduction and favorable biology of the tumor.