Completeness Of Cytoreduction Score Research Articles

Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC).

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival. A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied. Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months. The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.

Morbidity of the abdominal wall resection and reconstruction after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

CRS/HIPEC has evolved as a therapeutic option for selected patients with peritoneal surface malignancies. To achieve complete cytoreduction (CC), some patients require extensive abdominal-wall resection (AWR) and subsequent complex reconstructions, which may be associated with wound complications (WC) and delay of postoperative cancer therapy. Review of a prospective database of 350 patients revealed 213 patients with peritoneal carcinomatosis who underwent AWR due to suspected or proven wound/port site metastases during CRS/HIPEC. Tumor origin included: appendix, colon, ovarian, peritoneal mesothelioma, primary peritoneal, and others. WC were related to peritoneal carcinomatosis index (PCI), CC score, length of surgery, type of AWR and closure, blood transfusion, and albumin levels using binary logistic regression (odds ratios (OR) and 95% CIs) analysis. PCI≥20 was found in 151 (71%), CC was achieved in 178 (84%). Mean length of surgery was 613min. Postoperative WC were detected in 49 of 213 (23%) patients, 13 (6%) had Grade III (according to Clavien-Dindo's classification) WC, and led to delay of postoperative chemotherapy. WC occurred in 21 of 64 (32.8%) patients with excision of port sites (odds ratio [OR]=2.11, confidence interval [CI]=1.09-4.10, p=0.026). Primary fascial closure was performed in 191 of 213 (89.7%) patients, 40 (21%) of whom had WC. Mesh-assisted abdominal wall reconstruction was required in 22 of 213 (10.3%) patients, of whom 9 (40.9%) had WC (OR=2.61, CI=1.04-6.55, p=0.035). Port-site excision and mesh-assisted abdominal wall reconstruction were associated with higher incidence of postoperative WC following CRS/HIPEC. The implications of these preliminary findings may need to be considered during surgical planning for these patients.

Predictors of Progression in High-Grade Appendiceal or Colorectal Peritoneal Carcinomatosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Long-term survival of patients with appendiceal or colorectal peritoneal carcinomatosis (PC) may be achieved by combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, such favorable outcomes are realized in a minority of patients. Given the morbidity of the CRS/HIPEC and the uncertain role of postresection systemic therapy, it is important that prognostic factors in high-grade PC be clearly defined. This single center, retrospective, cohort study examined the outcomes of CRS/HIPEC performed on patients with high-grade PC secondary to appendiceal or colorectal adenocarcinoma between 2007 and 2013. Cox regression analysis was utilized to evaluate the association between potential prognostic factors [age, sex, primary site, lymph node (LN) status, peritoneal cancer index (PCI) score, completeness of cytoreduction score (CC score), number of visceral resections, and systemic chemotherapy] and progression-free survival (PFS). A total of 70 patients with high-grade appendiceal or colorectal PC underwent CRS/HIPEC during the study period; 82.9% underwent complete (CC-0) cytoreduction with a median PFS of 9.7months. Positive LNs at the time of CRS/HIPEC were predictors of worse PFS on univariate and multivariate analysis. No association was demonstrated between pre- or post-HIPEC systemic chemotherapy and PFS. High-grade PC secondary to appendiceal or colorectal adenocarcinoma can be managed with CRS/HIPEC. The number of LN metastases at the time of CRS/HIPEC is the strongest predictor of progression and must be considered when determining patient eligibility for this aggressive treatment.

Management of peritoneal carcinomatosis from colorectal cancer: review of the literature.

Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines. The present study is a review of the literature investigating current strategies to treat CRC PC. Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients. Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.

Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1,000 Patients

Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of endometrial cancer with peritoneal carcinomatosis

ObjectiveTo investigate the benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis. Study designPreoperative, intraoperative and postoperative data were collected prospectively for 13 patients treated in our University hospital. ResultsOf the thirteen patients treated, one patient was lost to follow up. Three patients died within the first twelve months of treatment, and two patients died at respectively 12.4 and 19.4 months after the HIPEC procedure. Seven patients are alive, four of them without recurrence, between 1.5 and 124.8 months after surgery. The Peritoneal Cancer Index (PCI) and the Completeness of Cytoreduction-Score (CC-S) are prognostic factors for survival after HIPEC treatment for peritoneal carcinomatosis of endometrial origin. ConclusionsThe significant survival time in selected patients should lead to a study of the management of peritoneal carcinomatosis of endometrial origin in a larger number of cases, and justifies a clinical trial on a larger scale.

The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer.

e15123 Background: Vascular endothelial growth factor receptor 2 (VEGFR-2) is considered a prognostic factor and treatment target for metastatic colorectal and ovarian cancer. Peritoneal Carcinomatosis (PC) from appendiceal cancer is a rare malignancy, treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), for which tumor histology, completeness of cytoreduction (CC), and lymph node (LN) status are predictors of survival. We hypothesize that high VEGFR-2 expression is a negative prognostic factor for survival in patients with PC from appendiceal cancer. Methods: A retrospective study of a prospective database was conducted in 127 patients with PC from appendiceal cancer who underwent CRS/HIPEC. Surgical specimens from a total of 59 patients were tested to identify “high” vs. “low” VEGFR-2 expression. Patients were divided into 2 groups: high VEGFR-2 expressers and low VEGFR-2 expressers. Patients’ outcomes and survival were analyzed. Results: There were 26 males and 33 females. Mean age was 51 years. Mean follow up of high and low expressers was 25.1 and 26.6, respectively (p = 0.806). At follow up, 33 (70%) of high expressers were alive and 14 (30%) deceased, while 11 (92%) of low expressers were alive and 1 (8%) deceased. Overall recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers and did not correlate with survival or outcome. OS for high expressers was 90.5%, 59.8, and 47.1% at 1-, 3-, 5-years (p = 0.133) respectively, while OS for low expressers was 91.7% at 1-, 3-, and 5-years. Conclusions: There is a trend toward better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. However, follow up is short and a larger number of patients is needed to confirm this trend and possibly correlate a high expression of VEGFR-2 to poorer outcomes and decreased survival in PC of appendiceal origin.

Assessment of Neoadjuvant Chemotherapy on Operative Parameters and Outcome in Patients with Peritoneal Dissemination from High-Grade Appendiceal Cancer

High-grade appendiceal adenocarcinoma is a rare malignancy with propensity for peritoneal metastases (PM). The impact of neoadjuvant chemotherapy on operative cytoreduction (CRS) and intraperitoneal chemotherapy (HIPEC) and patient survival was reviewed. A total of 45 patients with PM from high-grade appendiceal adenocarcinoma were identified from a prospective database. All patients had laparotomy with intent to undergo CRS and HIPEC. Operative parameters, complications, and survival outcomes were analyzed. Of the 45 patients (male: 27, female: 18; median age: 55years), 26 received neoadjuvant chemotherapy±bevacizumab. Of the 26, 15 (58%) had a response based on improvement in imaging, biomarkers, or both and 9 (34%) had stable disease. The median peritoneal cancer index (PCI) was 27. Also, 30 (67%) had a completeness of cytoreduction score (CCR) of ≤1 and 37 (82%) received HIPEC. There were no differences in PCI, CCR score, operative blood loss, or major organ resection between those who received or did not receive neoadjuvant chemotherapy. Operative time was significantly shorter in those who did not receive neoadjuvant chemotherapy. Major complications and length of hospital stay were similar between the groups. The median actuarial overall survival calculated from the date of initial therapeutic intervention was not different in those treated with or without neoadjuvant therapy. Neoadjuvant chemotherapy has marked clinical activity in patients with PM from high-grade appendiceal adenocarcinoma and does not adversely affect operative outcomes. These data support conducting a prospective clinical trial to define the role of neoadjuvant chemotherapy in this clinical setting.

The natural history and role of surgical cytoreduction and systemic chemotherapy in high-grade mucinous adenocarcinomas of the appendix.

199 Background: The natural history, clinical presentation, and impact of cytoreductive surgery (CRS) or systemic chemotherapy for high grade MAA has been poorly studied. Methods: A retrospective chart review of patients (pts) with moderate or poorly differentiated AA was completed from 1994-2010. Radiographic response was assessed semi-quantitatively form physician records and complete cytoreductive surgery (CRS) was defined as a completeness of cytoreduction score of 0 or 1. For CRS and chemotherapy subgroups efficacy endpoints were calculated from date of CRS or first chemotherapy dose, respectively. Results: 288 (136 moderate and 152 poor grade) pts were identified with a median age of 52 years (range: 25-82). Mucinous histology was present in 110 pts (38%) and differed by grade: 55% of moderate and 23% of poor. Stage IV presentation (n=163) occurred in 76% of poor grade but only 35% of moderate grade. Both median OS (4.5 vs. 2.7 yrs, P=0.04) and median OS for the stage IV subgroup (3 vs 1.9yrs, P=0.005) were improved for MAA vs. non-MAA. Moderate compared to poor grade had improved median OS (3.7 vs 1.9 yrs, P=0.002) for Stage IV disease, but this differed by mucinous histology (moderate mucinous 6.2yr vs. poor mucinous 1.6yr, P=0.001; moderate nonmucinous 1.4yr, poor nonmucinous 2yr). 39 MAA pts underwent a complete CRS (30 moderate and 9 poor) with a median time to recurrence of 1.5yrs and median OS of 9.2yrs. Improved OS was seen for pts with a complete CRS compared to pts with an incomplete CRS, P&lt;0.001. 55 MAA pts received systemic chemotherapy (fluoropyrimidine/oxaliplatin in 30, irinotecan-based in 8, fluoropyrimidine-based in 16, and other in 1): median OS of 2.1yr, median TTP of 7.2 months, and radiographic response of 36%. No statistical differences were seen between chemotherapy groups. Conclusions: High-grade MAA represents a heterogenous disease with a statistically worse OS for poor as opposed to moderate histological differentiation. This data does not support the AJCC 7th edition use of a single mucinous high-grade category. The use of systemic chemotherapy appears to be a viable treatment option for these pts and a complete CRS is associated with improved OS.

Comprehensive management of epithelial ovarian cancer with peritoneal metastases

Ovarian cancer has as its predominant pattern of dissemination metastases to the peritoneal surfaces and disease spread within the abdomen and pelvis that most commonly causes the patients demise. To combat peritoneal metastases, cytoreductive surgery with peritoneal and visceral resections is combined with intraperitoneal and systemic chemotherapy. Chemotherapy given in the operating room after the complete visible removal of ovarian cancer is hyperthermic intraperitoneal chemotherapy. The results of the combined treatment are determined by the extent of prior surgery, the extent of disease as established by the peritoneal cancer index, and the quality of the cytoreduction as measured by the completeness of cytoreduction score. Recent clinical information on patients with recurrent ovarian cancer suggest a median overall survival of up to 60 mo. These data are greatly improved over the one year survival observed in the past.

HIPEC + EPIC versus HIPEC‐alone: Differences in major complications following cytoreduction surgery for peritoneal malignancy

Peritoneal metastases (PM) can be treated with cytoreduction surgery (CRS) with intraoperative heated intraperitoneal chemotherapy (HIPEC) plus or minus early postoperative intraperitoneal chemotherapy (EPIC). HIPEC + EPIC may be associated with more complications than HIPEC alone. A prospective database of consecutive patients undergoing CRS + HIPEC ± EPIC at the University of Calgary between February 2000 and May 2011 was reviewed. Patient, tumor, and perioperative variables included peritoneal cancer index (PCI), completeness of cytoreduction (CCR) score, HIPEC ± EPIC type, and grade III/IV complications. 198 patients had a CCR score of 0/1 and received: (1) HIPEC mitomycin C + EPIC 5-fluorouracil for 5 days (n = 85; February 2000-January 2008); or (2) HIPEC oxaliplatin with IV 5-fluorouracil + no EPIC (n = 113; February 2008-May 2011). Clinicodemographics were similar except PCI was higher in the HIPEC-alone group (mean PCI 22 vs. 17; P = 0.02). The rate of grade III/IV complications was higher in the HIPEC + EPIC group (44.7% vs. 31.0%; P = 0.05). On multivariate logistic regression only HIPEC + EPIC and PCI > 26 were associated with an increased rate of complications. In patients with PM, the use of EPIC, in combination with CRS and HIPEC, is associated with an increased rate of complications. Surgeons should consider using HIPEC only (without EPIC).

Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix

Poorly differentiated and signet ring cell adenocarcinomas of the appendix represent a subset with aggressive tumor biology and poor outcomes with few studies evaluating the impact of systemic chemotherapy and cytoreductive surgery (CRS). A retrospective chart review of patients with either poorly differentiated and signet ring cell appendiceal adenocarcinomas was completed from 1992 to 2010. One hundred forty-two patients were identified. Seventy-eight patients with metastatic disease received chemotherapy. Radiographic response was 44%, median progression-free survival (PFS) was 6.9 months, and median overall survival (OS) was 1.7 years. In multivariate analysis, response to chemotherapy [hazard ratio (HR) 0.5; P = 0.02] predicted improved PFS, and complete CRS (HR 0.3; P = 0.004) predicted improved OS. Patients who underwent complete CRS (n = 26) had a median relapse-free survival (RFS) of 1.2 years and a median OS of 4.2 years. In multivariate analysis for this subset, complete cytoreduction score of 0 was significantly correlated with improved RFS (HR 0.07; P = 0.01) and OS (HR 0.02; P = 0.01). Systemic chemotherapy appears to be a viable treatment option for patients with metastatic poorly differentiated and signet ring cell appendiceal adenocarcinomas. Complete CRS is associated with improved RFS and OS, though part of this benefit likely reflects the selection of good tumor biology.

Aggressive Management of Peritoneal Carcinomatosis from Mucinous Appendiceal Neoplasms

Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons. We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes. Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0–21), 483.5 min (range, 46–1,402), and 800 ml (range, 0–14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox-regression model, tumor grade, age, preoperative SPCI and chemo-naïve status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression. Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity.

Prognostic and predictive effect of COX-2 expression in appendiceal adenocarcinomas.

526 Background: Cyclooxygenase-2 (COX-2), an inducible isoenzyme, is upregulated in inflammation and involved in cancer progression by promoting angiogenesis, cell proliferation and migration and by inhibiting apoptosis. COX-2 is implicated in colorectal tumorigenesis and by extension COX-2 expression testing and therapeutic inhibition has been considered in appendiceal adenocarcinomas (AAs). However, its role in this setting has never been well studied. The purpose of our study was to investigate COX-2 expression in AAs and to evaluate its prognostic and predictive significance. Methods: We performed a retrospective review of 607 patients with AAs treated at MD Anderson Cancer Center between 2002 and 2010. Immunohistochemistry was performed for COX-2 expression (COX2 mAb Clone CX229, Cayman Chemical) in 49 (8%) patients. Thirty (61%) stained positive and 19 (39%) showed no staining. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine association between OS, COX-2 expression and other characteristics. Results: Median age at diagnosis was 47 yrs (range 34-78 yrs). Grade (P = 0.003), completeness of cytoreduction score (P = 0.010) and stage (P = 0.023) were significantly associated with OS. Median OS for patients with COX-2 positive and COX-2 negative tumors was 58.3 and 42.8 months, respectively (P = 0.232). Nine COX-2 positive patients received celecoxib (selective COX-2 inhibitor) in combination with other chemotherapy. Mean treatment duration was 5.5 months with best radiographic response being stable disease in 7 patients. Reduction in tumor markers (CEA or CA19-9) was seen in 7 cases (median reduction of 30%). Similar treatment duration (6.6 months), rate of stable disease (6/8 pts) and tumor marker reduction (7/8 pts) was seen on the preceding non-celecoxib containing chemotherapy in these patients. Median OS, with and without COX-2 inhibition, was 55.7 and 57.6 months respectively (P = 0.57). Conclusions: In this cohort, COX-2 expression is not a significant prognostic factor in AAs. Benefit from COX-2 inhibition in COX-2 expressing AAs is unclear. Current data does not support the routine use of either COX-2 testing or COX-2 inhibition therapy in AAs.

Prognostic Significance of Lymph Node Metastases in Patients with High-Grade Appendiceal Cancer

In treating high-grade appendiceal cancer, appropriate patient selection for cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is essential. The effect of lymph node (LN) status on survival is not clear. We hypothesize that LN metastases negatively affect long-term survival. Retrospective analysis of peritoneal mucinous carcinomatosis (PMCA) patients from a prospective database was conducted. Using Kaplan-Meier survival curves and Cox proportional hazards ratio analysis, the effect of LN status, completeness of cytoreduction (CC), and peritoneal cancer index (PCI) was studied. Of 134 patients with appendiceal cancer who underwent CRS/HIPEC, 77 (57%) had PMCA. Mean follow-up was 22 (range, 3-90) months. Overall survival (OS) was 88, 56, and 40% for 1, 3, and 5-year, respectively. Thirty-four patients (44%) had LN metastases, 23 of whom (68%) had CC, whereas in LN negative patients 35 of 43 (81%) had CC (p=0.191). PCI≥20 was seen in 23 of 34 patients (68%) with LN metastases and 29 of 43 (67%) without metastases (p=0.191). Five-year OS for patients with LN metastases was 11% compared with 76% for LN negative (p<0.001). Among patients with complete cytoreduction, 5-year OS for LN positive vs. negative was 21 and 73%, respectively (p=0.002). On multivariate regression analysis of LN status, CC score and PCI, the following hazard ratios were obtained: 3.4 (95% confidence interval (CI), 1.3-9.0), 2.6 (95% CI, 1.03-6.7), and 2.8 (95% CI, 0.8-10.4), respectively. Patient selection for CRS/HIPEC should take into consideration LN status, but it should not be a contraindication if preoperative evaluation revealed a high likelihood of complete cytoreduction.

Appendiceal Adenocarcinoids with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy: A Retrospective Study of In Vitro Drug Sensitivity and Survival

The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (AAC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology. Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC. Patients with completeness of cytoreduction score (CC) ≤ 1 had better median survival (36.6 months) than those with CC > 1 (16.4 months). In the CC ≤ 1 group, 8 months elapsed between initial diagnosis and CRS with HIPEC compared with 22 months in the CC > 1 group. For standard drugs, tumor cells from AAC and CRC were equally sensitive; except for docetaxel, to which AAC was more sensitive than CRC. The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of AAC, although other drugs, eg, docetaxel, might be more active.

Clinical utility of elevated tumor markers in patients with disseminated appendiceal malignancies treated by cytoreductive surgery and HIPEC

Background Appendiceal malignancies with peritoneal spread have been successfully treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to clarify the utility of common tumor markers in selecting patients for the combined treatment. Methods Data on 56 patients with appendiceal neoplasms treated with CRS and HIPEC were prospectively collected. Chi square test was used to analyze a link between common tumor markers and completeness of cytoreduction score (CC score) and preoperative peritoneal cancer index score (PCI score). Cox proportional hazard model was used to perform survival analysis. Results Forty-two patients were alive after 3 years of follow-up. Hazard ratio of disease related death was 5.6 (95% CI, 1.8–17.2) among patients with high CC score as compared to those with low CC score. Number of abnormal tumor markers (0 vs 1/2/3) correlated with PCI score 16.2 vs 32.5 ( p < 0.001) but not with completeness of cytoreduction or survival. The 3-year survival rates in patients with normal vs abnormal CA 125 levels were 83% vs 52%( p = 0.003). Conclusions Multiple abnormal tumor markers were not useful as an exclusion criterion for patients undergoing CRS. Elevation in CA 125 was an important indicator of survival in these patients. Complete cytoreduction was crucial for long-term survival.

Complete Cytoreduction Offers Longterm Survival in Patients with Peritoneal Carcinomatosis from Appendiceal Tumors of Unfavorable Histology

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a rapidly evolving treatment for metastatic appendiceal neoplasms. The aim of this study was to show the effect of complete cytoreduction (CC) on survival in patients undergoing CRS and HIPEC for high-grade appendiceal neoplasm. A retrospective study of a prospective database of 56 patients (from 1999 to 2007) with appendiceal neoplasms treated with CRS and HIPEC was carried out. Histology of the disease, CC score, and peritoneal cancer index (PCI) score were assessed independently and collectively for each group of patients. Survival analysis was performed using the Cox proportional hazard model. Three-year overall survival was 60%. The median peritoneal cancer index score was 25 or higher. Survival analysis by tumor histology was 80% for patients with low-grade tumors and 52% for patients with high-grade tumors (p = 0.024). Survival by completeness of cytoreduction was 78% for patients with a low CC score (0 to 1) and 28% in patients with a high CC score (2 to 3; p = 0.01). There was no statistically significant difference in survival between the low-grade and high-grade tumors when a complete cytoreduction was performed in both groups of patients: 80% versus 68% (p = 0.69). CRS and HIPEC is an effective treatment for patients with disseminated appendiceal tumors. High-grade tumors also benefit from this approach and should not be excluded from CRS and HIPEC. Every effort should be made to achieve a complete cytoreduction regardless of the tumor histology.

Phase II study of regional treatment for peritoneal carcinomatosis

Background Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy is becoming an accepted treatment of carcinomatosis. Methods Between February 2000 and January 2008, there were 101 consecutive patients with carcinomatosis who were treated with cytoreductive surgery + hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patient and tumor characteristics, surgical details, complications, disease-free survival (DFS), and overall survival (OS) were recorded prospectively. Results The majority (82%) of patients, median age 49 years (range, 18–77 y), had complete macroscopic cytoreduction (completeness of cytoreduction score, 0) despite a generally extensive tumor burden. Perioperative mortality and grade III/IV morbidity rates were 4% and 39%, respectively. Preliminary median DFS and OS have not been defined for appendix tumors at a median follow-up period of 16 months (range, 1–86 mo). Median DFS and OS for colonic tumors are 8 months and 26 months, respectively, with a median follow-up period of 12 months (range, 1–48 mo). Conclusions Combined regional treatment is feasible and holds significant promise for the treatment of peritoneal carcinomatosis.

Postoperative residual disease evaluation in the locoregional treatment of peritoneal surface malignancy

The maximum size of the residual lesions left behind after cytoreductive surgery for peritoneal surface malignancy has consistently been shown to be the main prognostic factor in this setting. However, a uniform assessment method and categorization for this paramount prognostic indicator is lacking. In order to achieve a consensus among experts, the Delphi methodology was employed. Conflicting points were identified and related multiple choice questions were circulated among a panel of experts on peritoneal surface oncology. Two rounds of web-based voting were carried out. The completeness of cytoreduction (CC) Score described by Sugarbaker was considered the current best classification for residual disease size. The experienced surgeon's naked-eye estimation was considered the ideal method to assess residual disease size. There was agreement that the definition of CC-0 or R0 cytoreduction needs further specification. A redefinition of "completeness of cytoreduction" according to disease process was favored by the experts but not favored for the type of intraperitoneal chemotherapy employed. Following the experts' consensus, it is recommended that the CC score be used to categorize residual disease after cytoreductive surgery for peritoneal surface malignancy. Pending issues for further consensus development in this area have been identified.