Perioperative and Oncological Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis of Rectal Origin.

BACKGROUND: The peritoneum is a common metastatic site of colorectal cancer (CRC) and associated with worse oncological outcomes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve outcomes in selected patients. Studies have demonstrated significant difference in survival of patients with primary colon and rectal tumors both in local and in metastatic setting; but only few assessed outcomes of CRS/HIPEC for rectal and colon tumors. We studied the perioperative and oncological outcomes of patients undergoing CRS/HIPEC for rectal cancer. METHODS: A retrospective analysis of a prospectively maintained database between 2009 and 2021 was performed. RESULTS: 199 patients underwent CRS/HIPEC for CRC. 172 patients had primary colon tumors and 27 had primary rectal tumors. Primary rectal location was associated with longer surgery (mean 4.32, hours vs 5.26 h, p = 0.0013), increased blood loss (mean 441cc vs 602cc, p = 0.021), more blood transfusions (mean 0.77 vs 1.37units, p = 0.026) and longer hospitalizations (mean 10 days vs 13 days, p = 0.02). Median disease-free survival (DFS) was shorter in rectal primary group; 7.03 months vs 10.9 months for colon primaries (p = 0.036). Overall survival was not statistically significant; 53.2 months for rectal and 60.8 months for colon primary tumors. Multivariate analysis indicated origin (colon vs rectum) and Peritoneal Cancer Index to be independently associated with DFS. CONCLUSIONS: Patients with rectal carcinoma undergoing CRS/HIPEC for peritoneal metastasis had worse peri-operative and oncological outcomes. Overall survival was excellent in both groups. This data may be used for risk stratification when considering CRS/HIPEC for patients with rectal primary.

Increased risk for incisional hernia following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: The incidence of incisional hernias (IH) after midline laparotomy varies from 11% to 20%. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is potentially prone to hernias because a Xiphoid to pubis laparotomy incision performed on patients who have undergone previous abdominal surgeries with the addition of chemotherapy and its related adverse effects. METHODS: We performed a retrospective analysis on a prospectively maintained single institution database from March 2015 to July 2020. The inclusion criteria were patients who underwent CRS-HIPEC and had at least 6 months postoperative follow-up with post-operative cross-sectional imaging study. RESULTS: Two hundred and one patients were included in the study. All patients underwent CRS-HIPEC with resection of previous scar and umbilectomy. Fifty-four patients were diagnosed with IH (26.9%). The major risk factors for IH in multivariate analysis were higher American society of Anesthesiologists score (ASA) (OR 3.9, P = 0.012), increasing age (OR 1.06, P = 0.004) and increasing BMI (OR 1.1, P = 0.006). Most of the hernia sites were median (n = 43, 79.6%). Eleven (20.4%) patients had lateral hernias due to stoma incisions or drain sites. Most of the median hernias were at the level of the resected umbilicus 58.9% (n = 23). Five (9.3%) of the patients with IH necessitated an urgent surgical repair. CONCLUSION: We have demonstrated that more than a quarter of the patients after CRS-HIPEC suffer from IH and up to 10% of them may require surgical intervention. More research is needed to find the appropriate intraoperative interventions to minimize this sequela.

Pelvic Peritonectomy Poorly Affects Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Metastases.

BACKGROUND: Constraints of pelvic anatomy render complete cytoreduction (CRS) challenging. The aim of this study is to investigate the impact of pelvic peritonectomy during CRS/HIPEC on colorectal peritoneal metastasis (CRPM) patients' outcomes. METHODS: This is a retrospective analysis of a prospectively maintained CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) database. The analysis included 217 patients with CRPM who had a CRS/HIPEC between 2014 and 2021. We compared perioperative and oncological outcomes of patients with pelvic peritonectomy (PP) (n = 63) to no pelvic peritonectomy (non-PP) (n = 154). RESULTS: No differences in demographics were identified. The peritoneal cancer index (PCI) was higher in the PP group with a median PCI of 12 vs. 6 in the non-PP group (p < 0.001). Operative time was 4.9 vs. 4.3 h in the PP and non-PP groups, respectively (p = 0.63). Median hospitalization was longer in the PP group at 12 vs. 10 days (p = 0.007), and the rate of complications were higher in the PP group at 57.1% vs. 39.6% (p = 0.018). Pelvic peritonectomy was associated with worse disease-free (DFS) and overall survival (OS) with 3-year DFS and OS of 7.3 and 46.3% in the PP group vs. 28.2 and 87.8% in the non-PP group (p = 0.028, p .> 0.001). The univariate OS analysis identified higher PCI (p = 0.05), longer surgery duration (p = 0.02), and pelvic peritonectomy (p < 0.001) with worse OS. Pelvic peritonectomy remained an independent prognostic variable, irrespective of PCI, on the multivariate analysis (p < 0.001). CONCLUSIONS: Pelvic peritonectomy at the time of CRS/HIPEC is associated with higher morbidity and worse oncological outcomes. These findings should be taken into consideration in the management of patients with pelvic involvement.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Elderly is Safe and Effective.

INTRODUCTION: An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of our prospectively maintained CRS/HIPEC database analyzed perioperative and oncological outcomes of EP (>70 y) compared to younger patients (YP) (<60 y). RESULTS: Of 500 CRS/HIPEC patients, 62 EP and 210 YP were included. Median age was 73 y in EP and 46 y in YP. Demographic, clinical, operative, and perioperative outcomes were similar between groups. American Society of Anesthesiologists > 3 was more prevalent in the EP with 88.2% versus 54.8% in the YP (P < 0.001). Comorbidities were higher in the EP with 87.1% versus 39.0% in the YP (P < 0.001). Peritoneal Cancer Index score was similar with a median of 9. All postoperative and severe complications were similar with 55.2% and 17.1% in the YP and 64.5% and 21.0% in the EP (P = 0.242; P = 0.448). Postoperative mortality was similar with 1.5% in the YP and 5.0% in the EP (P = 0.134). In colorectal primary patients, median overall and disease-free survival was 61.8 and 12.9 mo in the YP and 64.6 and 11.3 mo in the EP (P = 0.363; P = 0.845). CONCLUSIONS: Despite a significant age difference, increased comorbidities, worse American Society of Anesthesiologists, and similar Peritoneal Cancer Index burden, we found no significant differences in perioperative complications or oncological benefit in elderly CRS/HIPEC patients. EP appear to have similar perioperative and oncological outcomes as YP.

Natural History and Management of Small-Bowel Obstruction in Patients After Cytoreductive Surgery and Intraperitoneal Chemotherapy.

BACKGROUND: Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis. METHODS: This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes. RESULTS: Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03). CONCLUSIONS: SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.

Outcomes of Stable Lung Colorectal Metastases on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival. We sought to evaluate the outcomes of patients undergoing CRS/HIPEC for peritoneal disease with known stable lung metastases. METHODS: We retrospectively reviewed our prospectively maintained CRS/HIPEC database. In 2017, we adopted a policy of considering patients with stable lung metastases for CRS/HIPEC as part of multidisciplinary treatment. We compared the oncologic outcome and safety of CRS/HIPEC with peritoneal only (PM) against patients with peritoneal and lung metastases (PLM). RESULTS: Our database includes 570 patients with CRS/HIPEC of which 174 with CRPM that underwent CRS/HIPEC, 18 with preoperatively diagnosed peritoneal and lung metastases. The demographics of the PM and PLM group were similar with the exception of operative time that was longer in the PLM group. Median PCI of the cohort was 7, similar in both groups (p = 0.89). Three-year overall survival (OS) of PLM patients was 68%, compared to 71% in PM (p = 0.277). Three-year progression-free survival (PFS) rate was 20% in PLM and 23% in PM (p = 0.688). CONCLUSIONS: Presence of stable lung metastases from colorectal cancer in patients with CRPM does not appear to affect the outcomes of CRS/HIPEC. Patients with stable lung disease should be considered for CRS/HIPEC after multidisciplinary discussion.

The impact of gastrointestinal anastomotic leaks on survival of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Gastrointestinal (GI) leaks after cytoreductive surgery and hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is a known life-threatening complication that may alter patients' outcomes. Our aim is to investigate risk factors associated with GI leaks and evaluate the impact of GI leaks on patient's oncological outcomes. METHODS: A retrospective analysis of perioperative and oncological outcomes of patients with and without GI leaks after CRS/HIPEC. RESULTS: Out of 191 patients included in this study, GI leaks were identified in 17.8% (34/191) of patients. Small bowel anastomoses were the most common site (44%). Most of the GI leaks were managed conservatively and re-operation was needed in 44.1% of cases. Univariate analysis identified higher PCI (p = 0.03), higher number of packed cells transfused (p = 0.036), pelvic peritonectomy (p = 0.013), high number of anastomoses (p = 0.003) and colonic resection (p = 0.042) as factors associated with GI leaks. Multivariate analysis identified stapled anastomoses (OR 2.59, p = 0.001) and pelvic peritonectomy (OR 2.33, p = 0.044) as independent factors associated with GI leaks. Disease-free survival tended to be worse in the leak group but did not reach statistical significance (p = 0.235). The 3- and 5-year OS was 73.2% and 52.9% in the leak group compared to 75.8% and 73.2% in the non-leak group (p = 0.236). CONCLUSIONS: GI leak showed no impact on overall and disease free survival after CRS/HIPEC.Avoidance of stapled reconstruction in high risk patients with high tumor burden and large number of anastomoses may yield improved outcomes.

Ratio of Pathological Response to Preoperative Chemotherapy in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer Correlates with Survival.

BACKGROUND: Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. RESULTS: The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001). CONCLUSIONS: The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Repeat Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Recurrences is Safe and Efficacious.

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) for colorectal cancer peritoneal metastases (CRPM) is associated with improved survival in patients with historically dismal prognosis. Nonetheless, peritoneal recurrences remain common and represent a difficult challenge in these patients' management. Repeat CRS/HIPEC is associated with even greater morbidity and its survival benefit has not yet been clearly demonstrated. METHODS: We retrospectively reviewed our prospectively maintained database and aimed to assess the safety and oncological efficacy of repeat CRS/HIPEC. RESULTS: Two hundred thirty-two patients underwent an initial CRS/HIPEC, whereas 30 subsequently had repeat CRS/HIPEC for CRPM. Groups were similar in demographics, comorbidities, and peritoneal cancer index (PCI). No significant difference in morbidity, hospital stay, or reoperation rate was noted between initial and repeat procedures. Patients who underwent repeat CRS/HIPEC had a median overall survival of 68 months versus 51 months in patients who did not undergo repeat procedure for their peritoneal recurrence (p = 0.03). Disease-free survival (DFS) in patients after repeat and after initial procedure were similar with median of 9.6 versus 12 months, respectively (p = 0.083). Univariate analysis demonstrated that PCI, DFS, and repeat procedure displayed significant factors on outcomes in patients with peritoneal recurrences, whereas PCI > 16 and DFS remained independent predictors on multivariable analysis. CONCLUSIONS: Our analysis, which represents the largest series to date of repeat CRS/HIPEC for CRPM, indicates that this approach as a part of multimodal therapy is both safe and efficacious in appropriately selected patients.

Perioperative and Oncological Outcomes of Combined Hepatectomy with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND: Synchronous peritoneal and liver metastasis in colorectal cancer is a relative contraindication for curative surgery. We aimed to evaluate the safety and oncological outcomes of combined treatment of peritoneal and liver metastasis. METHODS: We conducted a retrospective analysis of metastatic colorectal cancer patients from two prospective databases: peritoneal surface malignancy (n = 536) and hepatobiliary (n = 286). We compared 60 patients treated with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) and hepatectomy; 80 patients treated with cytoreduction and HIPEC only; and 63 patients treated with hepatectomy alone. RESULTS: No differences in demographics were observed between the groups. Median hospital and intensive care unit (ICU) stay was shorter in group C (7 and 1 days, respectively) versus groups A and B (13 and 1 days, and 12 and 1 days, respectively; p < 0.001). Postoperative complications were not significantly different. Median follow-up was 18.6, 23.1, and 30.6 months for groups A, B, and C, respectively. Estimated 5-year overall survival (OS) was 48.8% (group A), 55.4% (group B), and 60.2% (group C) [p = 0.043 for group A vs. group C], and estimated 5-year disease-free survival (DFS) was 14.2% (group A), 23.0% (group B), and 18.6% (group C). Five-year OS was superior in group C compared with group A (p = 0.043), and DFS was superior in group C compared with groups A and B (p = 0.043 and 0.03, respectively). The peritoneum was the site of first recurrence in groups A and B (23.3% and 32.5%, respectively), and the liver was the site of first recurrence in group C (44.4%). CONCLUSIONS: We report favorable perioperative and oncological outcomes in combined cytoreduction/HIPEC and hepatectomy for patients with peritoneal and liver metastasis. Surgical intervention after multidisciplinary discussion should be considered in patients with both peritoneal and hepatic lesions when complete cytoreduction is feasible.

[CYTOREDUCTIVE SURGERY AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) FOR PERITONEAL METASTASIS OF GASTRO-INTESTINAL ORIGIN].

INTRODUCTION: The management of peritoneal surface malignancies has changed dramatically. Moving, in less than two decades, from a nihilistic approach offering limited palliation and a short median survival into an aggressive surgical approach combining resection of all tumor deposits (cytoreductive surgery (CRS) combined with hyperthermic intra-peritoneal chemotherapy (HIPEC). This novel approach dramatically changed the outcome of this group of disorders offering a long term survival with curative intent to selected patients. The aim of the current review is to describe, based on current medical literature and our experience, current treatment options with CRS+HIPEC in various peritoneal surface malignancies of gastrointestinal origin, namely, colorectal cancer and appendiceal cancer, indications, technique, and outcomes.

Hospital readmission rates and risk factors for readmission following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies.

BACKGROUND: Cytoreductive surgery and Hyperthermic intra-peritoneal chemotherapy (CRS/HIPEC) for peritoneal surface malignancies is associated with high morbidity. The increased numbers of patients undergoing CRS/HIPEC in recent years mandates risk analysis and quality assurance. However, only scarce data exist regarding causative parameters for readmission. The aim of this study was to assess readmission rates and risk factors associated with readmission. METHODS: A retrospective-cohort study including patients from two high-volume centers who underwent CRS/HIPEC surgery between the years 2007-2016 was performed. Patients' demographics, peri-operative data and readmission rates were recorded. RESULTS: 223 patients were included in the study. The 7 and 30-day readmission rates were 3.5% (n = 8) and 11% (n = 25), respectively. Late readmission rates (up to 90 days) were 11% (n = 25). The most common causes of readmission were surgical related infections (35%), small bowel obstruction (17.5%) and dehydration (14%). Post-operative complications were associated with higher readmission rates (p = 0.0001). PCI score was not associated with higher rates of readmission. CONCLUSION: Readmissions following CRS/HIPEC occur mainly due to infectious complications and dehydrations. Patients following CRS/HIPEC should be discharged after careful investigation to a community based continuing care with access for IV fluid replacement or antibiotics administration when required.