Acute toxicity and surgical complications after preoperative (chemo)radiation therapy for rectal cancer in patients with inflammatory bowel disease.

PURPOSE: Preoperative therapy reduces local recurrences and may facilitate surgery in rectal cancer patients. However, in patients with inflammatory bowel disease (IBD) this treatment is often withheld due to the perceived risk of excessive side-effects, even though evidence is limited. The purpose of this study is to investigate the effects of preoperative therapy on acute toxicity and post-operative complications in IBD patients with rectal cancer. METHODS: The Dutch pathology registry (PALGA) was searched for patients with IBD and rectal cancer treated between January 1991 and May 2010. Histopathology and clinical charts were reviewed to confirm IBD diagnosis and evaluate clinical and pathological characteristics. RESULTS: Out of 161 patients, 66 received preoperative therapy (41%), including short-course radiation therapy (SC-RT), long course radiation therapy (LC-RT), and chemoradiation therapy (CRT) in 32, 13, and 21 patients respectively. Grade≥3 acute toxicity occurred in 0 patients (0.0%), 1 patient (7.7%), and 6 patients (28.6%) respectively (p=0.004). Systemic corticosteroids were used by 10.5% of patients at time of treatment. Grade≥3 post-operative 30-day complication rate (28.1% overall) was not associated with type of preoperative therapy. CONCLUSION: Results did not show excessive rates of toxicity or post-operative complications and support the use of standard preoperative therapies for rectal cancer (especially SC-RT) in IBD patients with relatively indolent disease. Caution is warranted in patients with active IBD, since the exact impact of active bowel inflammation could not be determined retrospectively. Prospective studies should investigate the influence of active IBD on acute and late toxicity in patients receiving pelvic irradiation.

Cytoreductive surgery and HIPEC offers similar outcomes in patients with rectal peritoneal metastases compared to colon cancer patients: a matched case control study.

BACKGROUND & OBJECTIVES: The effect of cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with rectal peritoneal metastases (PM) is unclear. This case-control study aims to assess the results of cytoreduction and HIPEC in patients with rectal PM compared to colon PM patients. METHODS: Colorectal PM patients treated with complete macroscopic cytoreduction and HIPEC were included. Two colon cancer patients were case-matched for each rectal cancer patient, based on prognostic factors (T stage, N stage, histology type, and extent of PM). Short- and long-term outcomes were compared between both groups. RESULTS: From 317 patients treated with complete macroscopic cytoreduction and HIPEC, 29 patients (9.1%) had rectal PM. Fifty-eight colon cases were selected as control patients. Baseline characteristics were similar between groups. Major morbidity was 27.6% and 34.5% in the rectal and colon group, respectively (P = 0.516). Median disease-free survival was 13.5 months in the rectal group and 13.6 months in the colon group (P = 0.621). Two- and five-year overall survival rates were 54%/32% in rectal cancer patients, and 61%/24% in colon cancer patients (P = 0.987). CONCLUSIONS: Cytoreduction and HIPEC in selected patients with rectal PM is feasible and provides similar outcomes as in colon cancer patients. Rectal PM should not be regarded a contra-indication for cytoreduction and HIPEC in selected patients. J. Surg. Oncol. 2016;113:548-553. © 2016 Wiley Periodicals, Inc.

Treatment-Related Mortality After Cytoreductive Surgery and HIPEC in Patients with Colorectal Peritoneal Carcinomatosis is Underestimated by Conventional Parameters.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as treatment for patients with colorectal peritoneal carcinomatosis (PC) is regarded as an extensive procedure. The risk of postoperative mortality after major abdominal surgery might be substantially higher than described by the 30-day mortality. This study aims to identify causes of 1-year mortality, thereby assessing a more accurate treatment-related mortality rate after CRS + HIPEC. METHODS: All subsequent patients with colorectal PC treated with CRS + HIPEC with complete macroscopic cytoreduction in two tertiary hospitals between April 2005 and April 2013 were included in this study. Causes of 1-year mortality were carefully analyzed and patient data were compared between patients who died or did not die within 12 months after CRS + HIPEC. RESULTS: Of the 245 included patients, 34 (13.9 %) died within 12 months after CRS + HIPEC. The overall treatment-related mortality rate was 4.9 % (n = 12), and the 30-day and in-hospital mortality rates were 1.6 % (n = 4) and 2.4 % (n = 6), respectively. Furthermore, 18 patients (7.3 %) died due to early recurrent disease. Three patients (1.2 %) died of cardiovascular events, unrelated to CRS + HIPEC. The 1-year mortality group had more extensive peritoneal disease (p = 0.02) and the operative time in this group was longer (p < 0.001). CONCLUSIONS: Overall treatment-related mortality was considerably higher than described by the 30-day and in-hospital mortality rate. However, even though complete macroscopic cytoreduction was achieved in every patient, the main cause of 1-year mortality was early recurrent disease. Both findings are valuable in preoperative patient selection, as well as in preoperative counseling of patients undergoing a CRS + HIPEC procedure.

Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: experiment or standard care? A survey among oncologic surgeons and medical oncologists.

BACKGROUND: Controversy still exists regarding the position of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis of colorectal carcinoma. The goal of the current study was to evaluate the opinions about this treatment among Dutch oncologic surgeons and medical oncologists. METHODS: An online survey was sent to all known Dutch oncologic surgeons (n = 459) and medical oncologists (n = 363) representing the respective departments of 84 hospitals. A comparison was made between surgeons and oncologists. RESULTS: 185 eligible responses were received from 71 hospitals, resulting in a response rate of 23 % for individuals and a response rate of 85 % for hospitals. Overall, 65 % of respondents regarded CRS+HIPEC as effective with sufficient evidence, 29 % responded that CRS+HIPEC is probably effective without sufficient evidence, and 7 % of respondents regards HIPEC as probably ineffective. Medical oncologists were less convinced of the effectiveness of CRS+HIPEC than surgeons (P = 0.006). Of all the respondents, 68 % indicated that they regard CRS+HIPEC as a standard treatment for patients with peritoneal dissemination of colorectal carcinoma (77 % of surgeons vs 54 % of oncologists, P = 0.001). Additionally, 68 % of respondents regard CRS+HIPEC as potentially curative (77 % of surgeons vs 54 % of oncologists, P = 0.001). CONCLUSIONS: Approximately 30 % of physicians who treat colorectal carcinoma do not regard CRS+HIPEC as standard care. Surgeons appear to be significantly more in favor of this treatment than medical oncologists. This study shows that efforts should be made to improve knowledge and increase acceptance of CRS and HIPEC in colorectal cancer treatment among medical oncologists and surgeons.

Peritoneal metastases from small bowel cancer: Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in The Netherlands.

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is currently considered the standard of care for pseudomyxoma peritonei, mesothelioma and peritoneal metastases (PM) from colorectal cancer. CRS + HIPEC has also been suggested as a potential treatment option in PM of the much rarer small bowel cancer. Therefore, the current study was undertaken to investigate the results of CRS + HIPEC in all HIPEC centers in The Netherlands. METHODS: From the 4 tertiary referral centers for peritoneal surface malignancies in The Netherlands, data from all patients with peritoneally metastasized small bowel carcinoma intended to undergo CRS and HIPEC were collected between January 2005 and July 2014. Primary tumor characteristics, operative details, and survival outcomes were collected. RESULTS: Sixteen of 19 patients (84.2%) who underwent explorative laparotomy underwent CRS + HIPEC. Of these patients, 81.3% were female, and primary tumors were mainly located in the ileum (50%). A complete macroscopic resection was achieved in 93.8%. Serious adverse events requiring re-intervention occurred in 25%, and no in-hospital mortality was observed. Recurrent disease was observed in 50% of patients and median survival after CRS and HIPEC was 31 months. CONCLUSION: In a select group of patients in whom a complete macroscopic resection can be achieved, survival rates comparable with those in colorectal PM are attainable with acceptable morbidity. The role of adjuvant chemotherapy needs further research.

Skeletal Muscle Depletion is Associated with Severe Postoperative Complications in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Cancer.

BACKGROUND: In patients undergoing colorectal cancer surgery, skeletal muscle depletion (sarcopenia) is associated with impaired postoperative recovery and decreased survival. This study aimed to determine whether skeletal muscle depletion can predict postoperative complications for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal carcinomatosis of colorectal cancer. METHODS: All consecutive patients with an available preoperative computed tomography (CT) scan who underwent CRS-HIPEC for peritoneal carcinomatosis of colorectal cancer in two centers were analyzed. Skeletal muscle mass was determined using the L3 muscle index on the preoperative CT scan. The cutoff values defined by Prado et al. were used to classify the patients as sarcopenic or nonsarcopenic. RESULTS: Of the study's 206 patients, 90 (43.7 %) were classified as sarcopenic. The sarcopenic patients underwent significantly more reoperations than the nonsarcopenic patients (25.6 vs. 12.1 %; p = 0.012). The mean L3 muscle index was significantly lower for the patients who experienced severe postoperative complications than for the patients without severe postoperative complications (85.6 vs. 110.2 cm(2)/m(2); p = 0.008). In a multivariable logistic regression model, L3 muscle index was the only parameter independently associated with the risk of severe postoperative complications (odds ratio 0.93; 95 % confidence interval 0.87-0.99; p = 0.018). CONCLUSION: Skeletal muscle mass depletion, assessed using CT-based muscle mass measurements, is associated with an increased risk of severe postoperative complications in patients undergoing CRS-HIPEC for colorectal peritoneal carcinomatosis and could therefore be used in preoperative risk assessment.

Urological procedures in patients with peritoneal carcinomatosis of colorectal cancer treated with HIPEC: morbidity and survival analysis.

AIM: To investigate whether cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is a feasible and effective option for patients with urological involvement of peritoneal carcinomatosis from colorectal cancer (CRC-PC). PATIENTS AND METHODS: The characteristics of patients with CRC-PC treated with CRS+HIPEC, with or without a urological procedure, between April 2005 and June 2013 in two tertiary Centres were analyzed. RESULTS: Thirty-eight patients (14%) out of 267 CRC-PC patients treated with CRS+HIPEC had a urological procedure during cytoreduction. The median survival was not significantly different between patients with or without a urological procedure (26.9 versus 32.1 months, p=0.29). Severe complications occurred more in patients with a urological procedure (47% versus 20%, p<0.001). In patients with a urological procedure, the most frequent complications were gastrointestinal leakage (n=9) and intra-abdominal abscess formation (n=5). CONCLUSION: Urological resections as a part of CRS+HIPEC in patients with peritoneal carcinomatosis of colorectal origin are feasible and effective. Severe complications are prevalent in these patients but survival is comparable to patients without involvement of the urinary system.

Patterns of recurrence following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer.

BACKGROUND AND OBJECTIVES: CytoReductive Surgery (CRS) combined with Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has an established role in the treatment of peritoneally metastasized colorectal cancer. The aim of the study was to describe the recurrence patterns and to evaluate treatment options and related survival. METHODS: Patients treated with CRS + HIPEC in two tertiary referral centers between April 2005 and March 2013 were analyzed retrospectively. The prognostic value of several parameters was calculated using Cox Regression. RESULTS: One hundred thirty two of 287 patients (46%) with peritoneal carcinomatosis treated with complete CRS and HIPEC were diagnosed with recurrent disease, after a median disease-free interval of 11.4 months. Recurrence were locoregional (43%), distant metastases (26%) or both (31%). Thirty-two of the 132 patients with recurrences (24%) were treated surgically with curative intent, which extended the median survival from 12 months to 43 months, compared to palliative treatment (best supportive care or chemotherapy; P < 0.001). Initial nodal status (P = 0.01) and the number of affected regions at initial CRS (P = 0.02) were significantly correlated to survival after disease recurrence. CONCLUSION: Disease recurrence after CRS and HIPEC is common; in selected patients, an aggressive surgical approach may be beneficial and extend survival.

Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis.

BACKGROUND: When peritoneal carcinomatosis (PC) is diagnosed during emergency surgery for colorectal cancer (CRC), further treatment with curative intent may seem futile given the known poor prognosis of both PC and emergency surgery. The aim of the current study was to investigate the feasibility and effectiveness of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC patients who previously underwent emergency surgery in the presence of PC. METHODS: All patients with synchronous PC of CRC referred to two tertiary centers between April 2005 and November 2013 were included in this study. Operative, postoperative and survival details were compared between patients presenting in an emergency or elective setting. RESULTS: In total, 149 patients with synchronous PC underwent CRS and HIPEC. Amongst these patients, 36 (24.2 %) initially presented with acute symptoms requiring emergency surgery. Acute presentation did not result in a longer interval between the initial operation and HIPEC (2.2 vs. 2.1 months; P = 0.09). When comparing operative outcomes, no significant differences were found in blood loss (P = 0.47), operation time (P = 0.39), or completeness of cytoreduction (P = 0.97). In addition, complication rates, degree and types of complication did not differ between the groups. Median survival was 36.1 months for emergency presentation compared with 32.1 in the elective group (P = 0.73). CONCLUSION: CRS + HIPEC may be performed safely in patients with PC of colorectal origin presenting with acute symptoms requiring emergency surgery. More importantly, the 5-year survival rate in these patients was equal to elective cases. This should be regarded as promising and therefore considered for these patients.