Disparities in Clinical Trial Participation: Multilevel Opportunities for Improvement.

Current data demonstrate ongoing inequities in surgical oncology clinical trials and understanding these disparities is vital to creating a more just and equitable health care system. Analysis of participatory patterns in cooperative group surgical oncology trials demonstrates complex relationships between race, socioeconomic status, and participation in these trials at the patient level. Further analysis reveals that provider-level implicit bias plays a significant role in access to clinical trials by minority populations. Holistic approaches to addressing disparities in clinical trial participation include creating a more robust pipeline of minority surgeon-scientists, engaging in partnerships with community advocates, and promoting public policy.

Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin.

BACKGROUND: This study evaluated health-related quality of life (HRQOL) using patient-reported outcomes in subjects with mucinous appendiceal neoplasms who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as part of a randomized trial comparing mitomycin with oxaliplatin. METHODS: In this prospective multicenter study, 121 mucinous appendiceal cancer patients, with evidence of peritoneal dissemination who underwent CRS, were randomized to receive mitomycin (divided 40 mg) or oxaliplatin (200 mg/m2) for HIPEC. The Functional Assessment of Cancer Therapy Neurotoxicity (FACT-G/NTX) questionnaire was utilized to assess HRQOL. The Trial Outcome Index (TOI) is a summary index responsive to changes in physical/functional outcomes. Repeated measures mixed models with an unstructured variance matrix were applied to assess changes in HRQOL longitudinally. RESULTS: Baseline questionnaire compliance was 95.9%. Baseline physical well-being (PWB) was independently associated with overall survival (hazard ratio 0.79, 95% confidence interval 0.66-0.96; p = 0.017). The TOI was significantly lower in the mitomycin group compared with the oxaliplatin arm at 12 weeks (p = 0.044; score difference 6.35) and 24 weeks after surgery (p = 0.049; score difference 5.61). At 12 weeks after surgery, declines from baseline were significant in the TOI (p = 0.004; score decline 8.99), PWB (p < 0.001; score decline 2.83), and FWB (p < 0.001; score decline 3.42) in the mitomycin group but not the oxaliplatin group. CONCLUSIONS: Compared with mitomycin, HIPEC perfusion with oxaliplatin results in significantly better physical and functional outcomes. With similar survival outcomes and complication rates, oxaliplatin should be considered as the chemoperfusion agent of choice in mucinous appendiceal cancer patients undergoing CRS/HIPEC.

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors.

BACKGROUND: Appendiceal cancer is a rare disease that has proven difficult to study in prospective trials. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established therapy for peritoneal dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use in the HIPEC is not clear. Mitomycin has long been used, however, our previous phase I experience and European retrospective studies suggest oxaliplatin as an alternative. Therefore, we initiated a multicenter randomized trial to compare mitomycin with oxaliplatin HIPEC for appendiceal cancer. STUDY DESIGN: Patients with mucinous appendiceal neoplasms with evidence of peritoneal dissemination underwent cytoreductive surgery and HIPEC using a closed technique for 120 minutes. Patients were randomized intraoperatively to HIPEC using mitomycin (40 mg) or oxaliplatin (200 mg/M2). Follow-up included daily blood counts and toxicity assessments. RESULTS: One hundred and twenty-one analytic patients were accrued to the trial during 6 years at 3 sites. The patients were 57% female, with a mean age of 55.3 years (range 22 to 82 years). The disease was low grade in 77% and high grade in 23%. There were no significant differences in hemoglobin or platelet counts. The WBC was significantly lower in the mitomycin group between postoperative days 5 and 10. Overall and disease-free survival rates at 3 years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for oxaliplatin. CONCLUSIONS: This represents the first completed prospective randomized trial for cancer of the appendix, and shows that multicenter trials for this disease are feasible. Both mitomycin and oxaliplatin are associated with minor hematologic toxicity. However, mitomycin has slightly higher hematologic toxicity and lower quality of life than oxaliplatin in HIPEC. Consequently, oxaliplatin might be preferred in patients with leukopenia and mitomycin preferred in patients with thrombocytopenia due to earlier chemotherapy.

Conditional Survival After Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy for Low- and High-Grade Appendiceal Primaries.

INTRODUCTION: Survival of patients after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy for appendiceal neoplasms is projected by conventional overall survival (OS) curves that do not address the survival time a patient has already accrued. We sought to study the conditional survival (CS) after CRS, contingent on patients surviving a fixed duration of time after surgery. METHODS: A retrospective analysis of 493 appendiceal cancer patients from a prospective database was performed. OS was calculated for patients who achieved a complete CRS. CS was estimated based on Kaplan-Meier curves to determine what the patient's long-term survival (3-, 5-, 7-, or 10-year) would be if they were alive at 1, 2, or 3 years from surgery. RESULTS: OS at 5 and 10 years for 137 low-grade patients with complete resections was 83.3 and 74.2 %, respectively. For low-grade patients still alive at 3 years, 5- and 10-year CS was 93.4 and 83.2 %, respectively. For the 35 high-grade patients with complete CRS who survived to 3 years, CS at 10 years was 41.7 %, while their 10-year conventional OS was 24.6 %. CONCLUSIONS: Conventional analysis underestimates OS due to unpredictable variations in tumor biology. When adjusted for time already elapsed since surgery, improvements in survival estimates are more pronounced with high-grade tumors. CS outcomes can be used in determining the optimal frequency of long-term follow-up of these patients.

Routine Admission to Intensive Care Unit After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: Not Always a Requirement.

BACKGROUND: Routine postoperative intensive care unit (ICU) observation of patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is driven by historically reported morbidity and mortality data. The validity of this practice and the criteria for ICU admission have not been elucidated. METHODS: A prospectively maintained database of 1146 CRS/HIPEC procedures performed from December 1991 to 2014 was retrospectively analyzed. Patients with routine postoperative ICU admission were compared with patients sent directly to the surgical floor. To test the safety of non-ICU care practice, patients with less than 48 h ICU admission were compared with patients directly admitted to the floor. Demographics, primary tumor site, comorbidities, estimated blood loss (EBL), extent of CRS, Eastern Cooperative Oncology Group (ECOG) status, and overall survival were analyzed. RESULTS: Complete data were available for 1064 CRS/HIPEC procedures, of which 244 cases (22.93 %) did not require ICU admission. Multivariate logistic regression identified age [odds ratio (OR) 1.024; p = 0.02], EBL (OR 1.002; p < 0.0001), number of resected organs (OR 1.308; p = 0.01) and ECOG > 2 (OR 6.387; p = 0.003) as predictive variables of postoperative ICU admission. The cohort directly admitted to the floor demonstrated less minor grade I/II morbidity (29 vs. 47 %; p < 0.0001) and similar grade III/IV major morbidity (16.5 vs. 13.4 %; p = 0.3) than the patients admitted to the ICU for less than 48 h. CONCLUSIONS: ICU observation is not routinely required for all patients treated with CRS/HIPEC. Selective ICU admission based on ECOG status, nutritional status, age, EBL, and CRS extent is safe, with potential implications for hospitalization cost for these complex cases.

Appendiceal goblet cell carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment commonly applied to peritoneal surface disease from low-grade mucinous tumors of the appendix. Some centers have extended this therapy to carcinomatosis from more aggressive malignancies. Therefore, we reviewed our experience with CRS/HIPEC for patients with goblet cell carcinomatosis. METHODS: Patients with carcinomatosis from appendiceal primaries with goblet cell features were identified in a prospectively maintained database of 1198 CRS/HIPEC procedures performed between 1991 and 2014. Patient demographics, disease characteristics, morbidity, mortality, and survival were reviewed. RESULTS: A total of 31 patients with carcinomatosis originating from appendiceal goblet cell tumors underwent CRS/HIPEC during the study period. Patients were generally young (mean age, 53 y) and otherwise healthy (84% without comorbidities) with good performance status (94% Eastern Cooperative Oncology Group 0 or 1). The mean number of visceral resections was 3.5, and complete cytoreduction of macroscopic disease was accomplished in 36%. Major 90-d morbidity and mortality rates were 38.7% and 9.7%, respectively. Median overall survival (OS) for all patients was 18.4 mo. Patients with negative nodes had better survival than those with positive nodes (median OS, 29.2 versus 10.2 mo), respectively (P = 0.002). Although complete cytoreduction was associated with longer median OS after CRS/HIPEC (R0/R1 28.6 versus R2 17.2 mo, P = 0.47), the observed difference did not reach statistical significance. CONCLUSIONS: CRS/HIPEC may improve survival in patients with node negative goblet cell carcinomatosis when a complete cytoreduction is achieved. Patients with disease not amenable to complete cytoreduction should not be offered CRS/HIPEC.

Significance of diabetes on morbidity and mortality following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Patients with diabetes suffering from peritoneal surface disease represent a challenge to treat due to the effects of both processes on multiple organ systems. We sought to define the impact of diabetes on outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A retrospective analysis of a prospective database of 1065 CRS/HIPEC procedures was conducted. Patient demographics, comorbidities, and tumor characteristics were reviewed. RESULTS: CRS/HIPEC was performed in 91 diabetic and 844 non-diabetic patients with peritoneal surface disease from 1991 to 2013. Diabetics and non-diabetics spent 6.8 and 3.1 (P = 0.009) days in the ICU, respectively. Diabetics were more likely to suffer major complications (P < 0.001) including infectious (P < 0.001) and thrombotic (P = 0.05) complications, arrhythmias (P = 0.007), renal insufficiency (P = 0.002) and respiratory failure (P = 0.002) than non-diabetics. Mortality was significantly worse for diabetic patients at 30-days (8.8% vs. 2.7%, P = 0.007) and at 90-days (13.2% vs. 5.2%, P = 0.008). Even after adjusting for other significant predictors of morbidity, diabetes predicted more major complications and increased mortality following CRS/HIPEC. CONCLUSIONS: Diabetes predicts major complications and specific complication patterns associated with increased ICU stay and worse mortality in patients undergoing CRS/HIPEC. Diabetic patients deemed to be appropriate candidates for CRS/HIPEC should be treated with caution.

Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): overview of 481 cases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal surface disease (PSD) from appendiceal cancer have shown variability in survival outcomes. The primary goal of this study was to determine predictors of surgical morbidity and overall survival. The secondary goal was to describe the impact of nodal status on survival after CRS/HIPEC for PSD from low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primary lesions. METHODS: A retrospective analysis of 1,069 procedures from a prospective database was performed. Patient characteristics, tumor grade, nodal status, performance status, resection status, morbidity, mortality, and survival were reviewed. RESULTS: The study identified 481 CRS/HIPEC procedures: 317 (77.3 %) for LGA and 93 (22.7 %) for HGA lesions. The median follow-up period was 44.4 months, and the 30-day major morbidity and mortality rates were respectively 27.8 and 2.7 %. Major morbidity was jointly predicted by incomplete cytoreduction (p = 0.0037), involved nodes (p < 0.0001), and comorbidities (p = 0.003). Multivariate negative predictors of survival included positive nodal status (p = 0.003), incomplete cytoreduction (p < 0.0001), and preoperative chemotherapy (p = 0.04) in LGA patients and incomplete cytoreduction (p = 0.0003) and preoperative chemotherapy (p = 0.0064) in HGA patients. After complete cytoreduction, median survival was worse for patients with positive nodes than for those with negative nodes in LGA (85 months vs not reached [82 % alive at 90 months]; p = 0.002) and HGA (30 vs 153 months; p < 0.0001). CONCLUSIONS: Positive nodes are associated with decreased survival not only for HGA patients but also for LGA patients even after complete cytoreduction. Nodal status further stratifies histologic grade as a prognostic indicator of survival. Patients with node-negative HGA primary lesions who receive a complete cytoreduction may experience survival comparable with that for LGA patients.

Impact of distal pancreatectomy on outcomes of peritoneal surface disease treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Left upper quadrant involvement by peritoneal surface disease (PSD) may require distal pancreatectomy (DP) to obtain complete cytoreduction. Herein, we study the impact of DP on outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Analysis of a prospective database of 1,019 procedures was performed. Malignancy type, performance status, resection status, comorbidities, Clavien-graded morbidity, mortality, and overall survival were reviewed. RESULTS: DP was a component of 63 CRS/HIPEC procedures, of which 63.3 % had an appendiceal primary. While 30-day mortality between patients with and without DP was no different (2.6 vs. 3.2 %; p = 0.790), 30-day major morbidity was worse in patients receiving a DP (30.2 vs. 18.8 %; p = 0.031). Pancreatic leak rate was 20.6 %. Intensive care unit days and length of stay were longer in DP versus non-DP patients (4.6 vs. 3.5 days, p = 0.007; and 22 vs. 14 days, p < 0.001, respectively). Thirty-day readmission was similar for patients with and without DP (29.2 vs. 21.1 %; p = 0.205). Median survival for low-grade appendiceal cancer (LGA) patients requiring DP was 106.9 months versus 84.3 months when DP was not required (p = 0.864). All seven LGA patients undergoing complete cytoreduction inclusive of DP were alive at the conclusion of the study (median follow-up 11.8 years). CONCLUSIONS: CRS/HIPEC including DP is associated with a significant increase in postoperative morbidity but not mortality. Survival was similar for patients with LGA whether or not DP was performed. Thus, the need for a DP should not be considered a contraindication for CRS/HIPEC procedures in LGA patients when complete cytoreduction can be achieved.

Peritoneal surface disease with synchronous hepatic involvement treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Patients with peritoneal surface disease (PSD) often present with synchronous hepatic involvement (HI). The impact of addressing the hepatic component during CRS/HIPEC on operative and survival outcomes is not clearly defined. METHODS: A prospective database of 1,067 procedures was reviewed based on primary tumor, performance status, resection status, type of liver involvement (superficial or parenchymal) and hepatic resection, morbidity, mortality, and overall survival. RESULTS: There were 108 (10 %) CRS/HIPEC procedures performed with synchronous liver debulking in 99 patients with PSD from 27 (33 %) appendiceal and 32 (39 %) colorectal primary lesions. Ninety percent of patients underwent subsegmental hepatic resection, whereas 22 % had disease with hepatic parenchymal involvement. Median intensive care unit (ICU) and hospital stay were 3.5 and 13.6 days, respectively. Clavien grade III/IV morbidity was similar for patients with or without resected HI (18.9 vs. 22.5 %; p = 0.39). The 30-day mortality rate was 6.5 and 2.8 % (p = 0.07) for patients with and without resected HI, respectively. The median survival for all patients with low-grade appendiceal cancer was 42.1 months with resected HI and 95.5 months without HI (p = 0.03). Median survival for colorectal cancer patients after complete cytoreduction was 21.2 months with HI versus 33.6 months without HI (p = 0.03). CONCLUSIONS: Synchronous resection of limited HI does not increase the morbidity or mortality of CRS/HIPEC procedures. The survival benefit, although still meaningful, was less for patients with HI. Resectable low volume HI in patients with PSD from colon and appendiceal primary lesions should not be considered a contraindication for CRS/HIPEC procedures.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in sarcomatosis from gastrointestinal stromal tumor.

The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) procedures in the management of patients with gastrointestinal stromal tumor (GIST)-induced sarcomatosis that is refractory to tyrosine kinase inhibitors (TKI) is not well defined. A retrospective analysis of a prospective database of 1070 CRS/HIPEC procedures was performed. Demographics, Eastern Cooperative Oncology Group performance status, resection status, morbidity, mortality, perioperative use of targeted therapies, and overall survival were analyzed. Since 1992, 18 CRS/HIPEC procedures were performed for peritoneal dissemination of GIST. Fifty per cent of these cases were performed before the introduction of TKIs. R0/1 resection was achieved in 72 per cent, whereas 63 per cent of patients were treated with neoadjuvant and/or adjuvant targeted therapy. Thirty-day morbidity and mortality were 33.3 and 5.6 per cent, respectively. Median overall survival after CRS/HIPEC was 3.33 years with 3-year survival of 56 per cent. Median survival in those who did not receive targeted therapy was 1.04 versus 7.9 years for those treated with TKI and cytoreduction. Median postsurgical survival for those treated preoperatively with progression on TKI treatment was 1.35 years versus not reached in those on TKI therapy without progression. Primary therapy for patients with disseminated GIST should be TKI therapy. However, in patients with sarcomatosis from GIST, cytoreduction should be considered before developing TKI resistance. Progression on TKI is associated with poor outcomes even after complete cytoreduction.

Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis.

Peritoneal metastasis (PM) has traditionally been approached with therapeutic nihilism. The evolution of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) over the last two decades, however, has caused a paradigm shift in treatment for PM. This modality is rapidly gaining acceptance as standard of care for PM from various cancers. This article reviews the current literature regarding the use of CRS/HIPEC for PM from the most common intra-abdominal malignancies.

Significance of diaphragmatic resections and thoracic chemoperfusion on outcomes of peritoneal surface disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Diaphragmatic resection (DR) during CRS/HIPEC exposes the thoracic cavity to direct contamination from the peritoneal cavity. The effect of thoracic chemoperfusion in combination with HIPEC in these patients is unknown. METHODS: A prospective database of 1,077 procedures was analyzed. Type of malignancy, thoracic perfusion, resection status, comorbidities, morbidity, mortality, and overall survival were reviewed. RESULTS: DR was a component of 102 CRS/HIPEC procedures performed for 57 (55.9 %) appendiceal and 22 (21.6 %) colon primary lesions. DR was associated with higher volume of disease as evidenced by more organ resections (3.7 vs. 2.8, p < 0.001) and increased rates of incomplete cytoreduction (67 vs. 52 %, p = 0.004). Patients with and without DR had similar 30-day major morbidity (23.5 vs. 16.8 %, p = 0.1) and worse 90-day mortality (12.8 % vs. 6.12 %, p = 0.03), respectively. Multivariate analysis showed DR (p = 0.01) and diabetes (p = 0.005) to be associated with worse mortality. Nineteen (20 %) DR patients underwent synchronous abdominal and thoracic chemoperfusion. Intrathoracic recurrence following DR with thoracic perfusion was 17 % (3/18) vs. 2.3 % (2/85) without perfusion (p = 0.04). Median survival following complete cytoreduction was similar for patients with low-grade appendiceal (LGA) (not reached with DR and 175 months without DR, p = 0.17) and colorectal cancer (23 months with and 31 months without DR, p = 0.76). CONCLUSIONS: Diaphragmatic resection during CRS/HIPEC is an independent predictor of surgical mortality. Intrapleural perfusion was associated with more thoracic recurrence; however, complete cytoreduction with or without DR can achieve similar survival for patients with LGA and colorectal primary lesions. DR should be performed only if careful inspection deems all peritoneal disease resectable.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gallbladder cancer: a retrospective review.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) often prolongs survival in patients with peritoneal surface disease, yet is generally avoided in patients with peritoneal spread from gallbladder cancer as a result of its aggressive biologic behavior. Therefore, we reviewed our experience with CRS/HIPEC for patients with gallbladder cancer. We retrospectively evaluated the outcomes of CRS/HIPEC procedures performed from 1991 to 2013 using a prospectively maintained database of 1069 procedures. Patient and tumor characteristics, morbidity, mortality, and survival were reviewed. CRS/HIPEC was performed six times in five patients with peritoneal spread from gallbladder cancer. Patients were young (age 28 to 54 years) without pre-existing comorbidities. Eighty per cent had an Eastern Cooperative Oncology Group score of 0 or 1. At CRS, organs resected included omentum (n = 4), liver (n = 3), colon (n = 2), ovaries (n = 1), and diaphragm (n = 1). A complete macroscopic cytoreduction of intraperitoneal disease was achieved in every case. Clavien graded major morbidity was 17 per cent. There was no observed mortality. Median and 3-year survival were 22.4 months and 30 per cent, respectively. CRS/HIPEC may be performed safely in patients with peritoneal dissemination from gallbladder cancer. Carefully selected patients with low-volume disease amenable to complete cytoreduction may experience a meaningful survival benefit.

Metastatic colorectal cancer: survival comparison of hepatic resection versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Liver resection has long been considered the standard of care for resectable colorectal hepatic metastases (HM). Patients with colorectal peritoneal surface disease (PSD) are now also being treated with aggressive therapy in the form of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective comparison of optimally-treated colorectal cancer patients with HM or PSD obtained from prospectively maintained databases (1991-2010). RESULTS: Liver resection was performed on 179 patients with HM, while 93 PSD patients received a complete cytoreduction followed by HIPEC. Patients differed in terms of age, performance status, site of primary cancer, T stage, and the use of perioperative chemotherapy. Five-year overall survival for HM patients was 36 %, with a median survival of 46 months, compared with 26 % and 34 months in patients with PSD (p = 0.024). When stratified by resection status, R0 HM (n = 170) and R0 PSD (n = 48) patients had similar median survival (49 vs. 41 months; p = 0.39). Median survival following R1 resection was also similar among HM (n = 9) and PSD (n = 45) patients (28 vs. 23 months; p = 0.68). Multivariate analysis identified distinctly different independent prognostic factors between HM and PSD patients. Major morbidity was 21 and 23 % (p = 0.88), while mortality was 3.9 versus 5.4 % (p = 0.55) in the HM and PSD patients, respectively. CONCLUSION: Colorectal HM and PSD are distinct biologic diseases with different presentations and unique prognostic factors. However, long-term survival following CS/HIPEC is comparable to liver resection when stratified by completeness of resection. Furthermore, perioperative morbidity and mortality are similar.

Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Perioperative systemic chemotherapy for appendiceal mucinous carcinoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The role of systemic chemotherapy (SC) in conjunction with cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in appendiceal mucinous carcinoma peritonei (MCP) is unknown. METHODS: A retrospective review (1999-2011) of MCP patients who had undergone CS/HIPEC with or without perioperative SC. RESULTS: Twenty-two low-grade MCP patients treated with CS/HIPEC and SC were matched to patients who received CS/HIPEC alone. Median overall survival (OS) was 107 months for patients treated with perioperative SC compared to 72 without (P = 0.46). CS/HIPEC was performed on 109 patients with high-grade MCP: 70 were treated with perioperative SC, while 39 were not. Median OS (22.1 vs. 19.6 months, P = 0.74) and progression-free survival (PFS) (10.9 vs. 7.0 months, P = 0.47) were similar in patients treated with SC compared to CS/HIPEC alone. Progression while on pre-operative SC was seen in eight patients (17%), while four (8%) had a partial response. Treatment with post-operative SC was associated with longer PFS (13.6 months) compared to pre-operative SC (6.8 months, P < 0.01) and CS/HIPEC alone (7.0 months, P = 0.03). CONCLUSIONS: Post-operative SC appears to improve PFS in patients with high-grade appendiceal MCP treated with CS/HIPEC. In contrast, there is no evidence to support the routine use of perioperative SC in low-grade disease.

Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites.

BACKGROUND: In peritoneal surface disease, accumulation of malignant ascites represents a difficult problem to treat, with adverse impact on quality of life. The role of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites is not well defined. METHODS: A retrospective analysis of a prospectively maintained database of 1,000 procedures was performed. Type of malignancy, resolution of ascites, duration and agent of chemoperfusion, performance status, resection status, morbidity, mortality, and survival were reviewed. RESULTS: Ascites was found in 299 patients (310 procedures) either before or during exploration. A total of 142 (46 %) procedures were performed for appendiceal primary disease, 53 (17 %) colorectal, 20 (6 %) gastric, 45 (15 %) mesothelioma, and 26 (8 %) ovarian. A total of 288 (93 %) patients had resolution of ascites by 3 months' follow-up. In patients with ascites, complete cytoreduction was obtained in 15 versus 59 % when ascites was not present (p < 0.001). In the group of patients who had their ascites controlled, 243 of 288 (84 %) had resection with residual macroscopic disease (R2 status). Twenty-two patients (7 %) had persistent ascites at 3 months' follow-up, 19 (86 %) of whom had an R2 resection. Univariate analysis revealed that type of primary disease, resection status, duration or agent of chemoperfusion, and performance status did not predict failure. CONCLUSIONS: CRS-HIPEC is effective in controlling ascites in 93 % of patients with malignant ascites, even when a complete cytoreduction is not feasible. Ascites is predictive of incomplete cytoreduction and worse overall survival. Although complete cytoreduction remains the goal of this procedure, HIPEC can provide palliative value in selected patients with malignant ascites.

Significance of urinary tract involvement in patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Urinary tract involvement in patients with peritoneal surface disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often requires complex urologic resections and reconstruction to achieve optimal cytoreduction. The impact of these combined procedures on surgical outcomes is not well defined. METHODS: A prospective database of CRS/HIPEC procedures was analyzed retrospectively. Type of malignancy, performance status, resection status, hospital and intensive care unit stay, morbidity, mortality, and overall survival were reviewed. RESULTS: A total of 864 patients underwent 933 CRS/HIPEC procedures, while 64 % (550) had preoperative ureteral stent placement. A total of 7.3 % had an additional urologic procedure without an increase in 30-day (p = 0.4) or 90-day (p = 1.0) mortality. Urologic procedures correlated with increased length of operating time (p < 0.001), blood loss (p < 0.001), and length of hospitalization (p = 0.003), yet were not associated with increased overall 30-day major morbidity (grade III/IV, p = 0.14). In multivariate analysis, independent predictors of additional urologic procedures were prior surgical score (p < 0.001), number of resected organs (p = 0.001), and low anterior resection (p = 0.03). Long-term survival was not statistically different between patients with and without urologic resection for low-grade appendiceal primary lesions (p = 0.23), high-grade appendiceal primary lesions (p = 0.40), or colorectal primary lesions (p = 0.14). CONCLUSIONS: Urinary tract involvement in patients with peritoneal surface disease does not increase overall surgical morbidity. Patients with urologic procedures demonstrate survival patterns with meaningful prolongation of life. Urologic involvement should not be considered a contraindication for CRS/HIPEC in patients with resectable peritoneal surface disease.