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 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.

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.

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.

Obesity and peritoneal surface disease: outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendiceal and colon primary tumors.

BACKGROUND: It is estimated that 37% of the U.S. population is obese. It is unknown how obesity influences the operative and survival outcomes of cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) procedures. METHODS: A retrospective analysis of a prospective database of 1,000 procedures was performed. Type of malignancy, performance status, resection status, hospital and intensive care unit stay, comorbidities, morbidity, mortality, and survival were reviewed. RESULTS: A total of 246 patients with body mass index (BMI) of >30 kg/m(2) underwent 272 CRS/HIPEC procedures. Ninety-five (38.6%) were severely obese (BMI > 35 kg/m(2)). A total of 135 (49.6%) procedures were performed for appendiceal and 60 (22.1%) for colon cancer. Median follow-up was 52 months. Both major and minor morbidity were similar for obese and non-obese patients. The 30-day mortality rates for obese and non-obese patients were 1.5 and 2.5%, respectively. Median intensive care unit and hospital stay were 1 and 9 days, regardless of BMI. The 30-day readmission rate was similar between obese and non-obese patients (24.8 vs. 19.4%, p = 0.11). Median survival for low-grade appendiceal cancer (LGA) was 76 months for obese patients and 107 months for non-obese patients (p = 0.32). Survival was worse for severely obese patients (median survival 54 months) versus non-obese patients with LGA (p = 0.04). Survival was similar for obese and non-obese patients with peritoneal surface disease (PSD) from colon cancer or high-grade appendiceal cancer. CONCLUSIONS: Obesity does not influence postoperative morbidity or mortality of patients with PSD, regardless of primary tumor. Severe obesity is associated with decreased long-term survival only in patients with LGA primary disease; however, application of CRS/HIPEC still offers meaningful prolongation of life. Obesity should not be considered a contraindication for CRS/HIPEC procedures.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal sarcomatosis.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the treatment most likely to achieve prolonged survival for peritoneal surface disease from various primaries, yet management of peritoneal sarcomatosis is controversial as a result of the propensity of sarcomas for hematogenous spread and the paucity of effective chemotherapy. Therefore, we reviewed our experience in patients with sarcomatosis. A retrospective analysis of a prospective database of 990 procedures was performed. Eastern Cooperative Oncology Group, age, type of primary, resection status, morbidity, mortality, and outcomes were reviewed. Over 20 years, 17 cytoreductions for sarcomatosis were performed. After excluding patients with gastrointestinal stromal tumor or uterine leiomyosarcoma, 10 procedures performed in seven patients remained. Median follow-up was 84.8 months. R0/1 resection was achieved in 60 per cent. The 30-day morbidity was 50 per cent; no operative mortality rate was observed. R2 resection had no long-term survivors. The reason for death was peritoneal recurrence in 57 per cent. Median survival was 21.6 months and five-year survival was 43 per cent. Median survival for patients with peritoneal sarcomatosis treated with CRS-HIPEC is similar with the historical reported survival before introducing chemoperfusion. Although a complete cytoreduction is related to improved survival, the role of HIPEC in these patients is unknown. A multi-institutional review will help define the role of CRS-HIPEC in this population.