Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. METHODS: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P<0.001). On multivariate analysis, UP was not associated with in-hospital mortality (2.7% vs. 1.7%, P=0.407) or grade III/IV morbidity (52% vs. 41%, P=0.376). The incidence of ureteric fistula (4% vs. 1%, P=0.004), return to theater (26% vs. 14%, P=0.005) and digestive fistula (22% vs. 11%, P=0.005) was higher in the UP group. The addition of a UP did not significantly impact overall survival for appendiceal cancer (P=0.162), colorectal cancer (P=0.315), or pseudomyxoma peritonei (P=0.120). CONCLUSIONS: Addition of a UP was not associated with an increased risk of grade III/IV morbidity or poorer long-term survival after CRS/HIPEC.

Recurrence and Survival Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Small Bowel Adenocarcinoma.

BACKGROUND: Peritoneal dissemination of small bowel adenocarcinoma (SBA) is rare but is associated with a dismal prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising treatment option. We evaluated our experience of CRS-HIPEC for the treatment of SBA. PATIENTS AND METHODS: Sixteen consecutive patients underwent CRS-HIPEC for small bowel malignancy between 2003 and 2016. Clinopathological and treatment-related factors were obtained from a prospective database. The study's endpoints of disease-free (DFS) and overall (OS) survival were evaluated using the Kaplan-Meier method. Prognostic variables were identified through univariate and multivariate analyses. RESULTS: Follow-up was complete in all patients. The median follow-up was 20.6 (range=0.2-62) months. The was no in-hospital mortality and grade III/IV morbidity was 25%. The median OS after CRS-HIPEC was 24.7 months, with a 36-month survival of 34%. The median DFS was 11.3 months, with a 36-month DFS of 8%. Two factors were associated with a poorer OS on univariate analysis; only peritoneal cancer index >10 was associated with a poorer OS on multivariate analysis (p=0.032). CONCLUSION: CRS-HIPEC in selected patients with peritoneal dissemination of SBA is associated with reasonable mid-term survival outcomes but treatment failure is common. High disease burden, quantified by the PCI is associated with poor outcomes. A large, prospective, multi-institutional study is needed to further evaluate the outcomes of CRS-HIPEC for SBA.

Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.

INTRODUCTION: There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units). Peri-operative complications were graded according to the Clavien-Dindo classification. The association of concomitant MABT with 21 peri-operative outcomes and overall survival (OS) was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring MABT had more extensive disease as reflected by a higher peritoneal cancer index (≥17) (70 vs. 29%, p < 0.001) and longer operative times (≥9 h) (82 vs. 35%, p < 0.001). After accounting for confounding factors, MABT was associated with in-hospital mortality (relative risk (RR), 7.72; 95% confidence interval (CI), 1.35-10.11; p = 0.021) and grade III/IV morbidity (RR, 2.05; 95% CI, 1.42-2.95; p < 0.001). MABT was associated with an increased incidence of prolonged hospital stay (≥28 days) (RR, 1.86; 95% CI, 1.26-2.74; p = 0.002) and intensive care unit stay (≥4 days) (RR, 1.83; 95% CI, 1.24-2.70, p = 0.002). It was also associated with a significant OS in patients with colorectal cancer peritoneal carcinomatosis (RR 4.49; p < 0.001) and pseudomyxoma peritonei (RR, 4.37; p = 0.026), but not appendiceal cancer (p = 0.160). CONCLUSION: MABT is an independent predictor for poorer peri-operative outcomes including in-hospital mortality and grade III/IV morbidity. It may also compromise long-term survival, particularly in patients with colorectal cancer peritoneal carcinomatosis.

Quality of life after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy for peritoneal carcinomatosis: A systematic review and meta-analysis.

OBJECTIVE: To review the effect of cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) on health-related quality of life (HRQOL) in patients with peritoneal carcinomatosis. BACKGROUND: CRS and HIPEC is increasingly performed with curative intent for peritoneal carcinomatosis. Significant morbidity rates are reported in the context of limited life-expectancy, necessitating accurate post-operative HRQOL outcome data. METHODS: A systematic review of clinical studies published after January 2000 was performed using strict eligibility criteria. Key outcomes measures were post-operative HRQOL compared to pre-operative levels and reference populations. Quality appraisal and data tabulation were performed using pre-determined forms. Data were synthesised by narrative review and random-effects meta-analysis. Tau2 and I2 values and Funnel plots were analysed for consistency and bias. RESULTS: 15 studies (1583 patients) were included. HRQOL declines at the 3-4 month time-point before becoming similar or better compared to pre-operative levels at 1 year. The pooled-effects of combined post-operative functional assessment of cancer therapy and European organisation for research and treatment quality of life questionnaire scores were significantly improved from baseline on overall health status (p=0.001) and emotional health (p=0.001). Physical health (p=0.83), social health (p=0.48) and functional health (p=0.24) remain similar. HRQOL after 1 year is less clear, but benefits may persist up to 5 years especially on overall and physical health domains. Evidence is conflicted and inconclusive on HRQOL compared to reference populations. Levels of consistency and bias were acceptable. CONCLUSIONS: CRS and HIPEC for peritoneal carcinomatosis can confer small to medium benefits for HRQOL. These results should be interpreted with in caution due to the small studies and absence of more randomised controlled trials.

Evolution of locoregional treatment for peritoneal carcinomatosis: single-center experience of 308 procedures of cytoreductive surgery and perioperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis imposes an enormous clinical burden to the oncologic community. This study reports the patterns of care of the locoregional approach of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy as a curative procedure for peritoneal carcinomatosis from the experience of a single tertiary center in Australia. METHODS: We performed a review of clinical records from a prospective database of patients who were treated at the St George Hospital Peritoneal Surface Malignancy Program according to a standard protocol. RESULTS: A total of 308 CRS were performed in 249 patients with peritoneal surface malignancy; the mean age was 53 years and 55% were women. Over the years, we expanded the age limit for treatment (P = .03), reduced intensive care unit stays (P = .04), reduced amount of blood transfusion (P = .03), treated patients with a higher peritoneal cancer index (P < .001), achieved higher rates of complete cytoreduction (P = .003), increased use of PIC (P < .001), and improved complication rate (P = .02) and mortality rate (P = .01). The median survival of patients treated over the years also improved (P = .001). CONCLUSIONS: We show the maturity of the treatment of peritoneal carcinomatosis with CRS and perioperative intraperitoneal chemotherapy in our institution after an initial learning curve with expansion of the selection criteria, improved perioperative outcomes, improved surgical results, and long-term survival outcomes.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. PATIENTS AND METHODS: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. RESULTS: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. CONCLUSION: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

A critical evaluation of risk factors for complications after cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected patients with colorectal peritoneal carcinomatosis (CRPC). This treatment modality is associated with relatively high rates of perioperative morbidity and mortality. This study evaluated the clinical and treatment-related risk factors for perioperative morbidity and mortality in patients with CRPC who underwent CRS and PIC. METHODS: Sixty-three consecutive patients who underwent CRS and PIC for CRPC were evaluated. Adverse events were rated from grades I to V with increasing severity. Clinical and treatment-related risk factors for grades III and IV/V morbidity were determined. RESULTS: There were no perioperative deaths (0%). The grades III and IV morbidity rates were 14 and 17%, respectively. A peritoneal cancer index >12 (p = 0.019), transfusion >4 units (p = 0.028), number of peritonectomy procedures >3 (p = 0.013), left upper quadrant peritonectomy procedure (p < 0.001), and number of primary colonic anastomosis >1 (p = 0.004) were associated with grade IV morbidity on univariate analysis. Only left upper quadrant procedure was associated with grade IV morbidity on multivariate analysis (p = 0.002). Only number of primary colonic anastomosis >1 (p = 0.037) was associated with grade III morbidity on univariate analysis. This also was associated with grade III morbidity on multivariate analysis (p = 0.028). CONCLUSIONS: CRS and PIC has an acceptable risk of perioperative morbidity in carefully selected patients with CRPC. Patients who require extensive surgery have the highest risk for a severe adverse event. Preoperative evaluation of patients is essential to improve perioperative outcome.

Evaluation of the cost-effectiveness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (peritonectomy) at the St George Hospital peritoneal surface malignancy program.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are treatment approaches for peritoneal carcinomatosis that has demonstrated improved survival outcomes with acceptable complication rates. This report aims to measure and describe the survival outcomes and health care cost associated with CRS and HIPEC for peritoneal surface malignancies at a centralized tertiary institution in Australia. METHODS: The expenditure of treatment for 136 consecutive patients who underwent 159 CRS and HIPEC from June 2002 to June 2008 were obtained. Together with their survival outcomes from treatment, a cost-effectiveness analysis was performed. RESULTS: The average cost of CRS and HIPEC per patient and per life year for appendix cancer is AUD $88,423 (range, AUD $23,933-AUD $299,145) and AUD $37,737/LY; for colorectal cancer is AUD $66,148 (range, AUD $26,079-AUD $409,666) and AUD $29,757/LY; for pseudomyxoma peritonei is AUD $92,308 (range, AUD $11,562-AUD $501,144) and AUD $29,559/LY; for peritoneal mesothelioma is AUD $55,062 (range, AUD $23,261-AUD $94,104) and AUD $20,521/LY; and for other peritoneal surface malignancies is AUD $44,668 (range, AUD $31,592-AUD $70,026) and AUD $22,091/LY. CONCLUSIONS: This complex surgical treatment results in significant increases in medical costs with a parallel increase in survival for a disease that has been poorly treated, and hence may be considered as cost-effective given the observed life years gained.

Risk factors for massive blood transfusion in cytoreductive surgery: a multivariate analysis of 243 procedures.

BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected patients with peritoneal carcinomatosis (PC). This treatment modality is associated with high blood loss and often requires massive allogenic red blood cell transfusion (MABT). Our study is the first of its kind to evaluate the risk factors for intraoperative MABT in peritonectomy procedures. METHODS: Two hundred and forty-three consecutive CRS and PIC procedures were evaluated. The associations between 17 preoperative and intraoperative risk factors and intraoperative MABT (>or=6 units) were assessed by univariate and multivariate analysis. RESULTS: One hundred and eighty-six (77%) procedures required intraoperative transfusion of packed red blood cells. Ninety-one procedures required MABT (37%). Multivariate analysis showed six significant risk factors for intraoperative MABT: operative length > 9 h (p < 0.001), preoperative hemoglobin < 125 g/l (p < 0.001), operation date prior to 2004 (p = 0.002), peritoneal cancer index >or= 16 (p = 0.006), preoperative international normalized ratio (INR) >or= 1.2 (p = 0.008), and number of peritonectomy procedures >or= 4 (p = 0.021). Statistical analysis also revealed that MABT was associated with increased intensive care unit (ICU) (p < 0.001), high-dependency unit (HDU) (p = 0.020), and total hospital stay (p < 0.001) and with severe morbidity (p < 0.001). CONCLUSIONS: Patients with preoperative anemia, impaired coagulation profile or extensive tumor burden are at high risk of MABT. Appropriate blood conservation strategies should be adopted in these patients on the basis of their risk factors.

Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality.

BACKGROUND: : Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been offered in many institutions worldwide since the 1990s. Despite its existence of more than 10 years, this treatment has received heavy criticism for its morbidity and mortality rates. This consequentially resulted in a lack of randomized trials being conducted and translates into a lack of the most reliable form of scientific evidence in clinical research, hence limiting its general acceptance. OBJECTIVE: : To report the morbidity and mortality outcomes of CRS and HIPEC from all institutions performing this treatment as a prelude toward establishing the safety of this treatment for peritoneal carcinomatosis. METHODS: : A systematic review of relevant studies before August 2008 was performed. Each study was appraised using a predetermined protocol. The quality of studies was assessed. The morbidity and mortality of the treatment were synthesized through a narrative review with full tabulation of results of all included studies. CONCLUSIONS: : The morbidity and mortality outcomes of CRS and HIPEC are similar to a major gastrointestinal surgery, such as a Whipple's procedure. To derive the maximal benefit of this treatment, careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment.