Oncological impact of intraperitoneal chemotherapy after cytoreductive surgery for patients with colorectal peritoneal metastasis: A bi-institutional retrospective analysis.

BACKGROUND AND OBJECTIVES: There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS. METHODS: The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS). RESULTS: In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications. CONCLUSIONS: Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.

Effect of preoperative immunonutrition on outcomes of colon cancer surgery: study protocol for a randomized controlled trial.

BACKGROUND: Current guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer. METHODS/DESIGN: Patients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm). DISCUSSION: Although there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer. TRIAL REGISTRATION: Clinical Research Information Service KCT0003770 . Registered on 15 April 2019.

Adjuvant chemoradiotherapy instead of revision radical resection after local excision for high-risk early rectal cancer.

BACKGROUND: After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. METHODS: Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. RESULTS: The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). CONCLUSIONS: In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

OBJECTIVE: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. PATIENTS AND METHODS: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. RESULTS: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). CONCLUSIONS: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

Prognostic value of perineural invasion in patients with stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) may influence the prognosis after resection of colorectal cancer (CRC); whether this is a definite prognostic factor remains controversial. This study determined the clinicopathologic factors associated with oncologic outcome after radical resection of stage II CRC, focusing on PNI. MATERIALS AND METHODS: We retrospectively reviewed 341 consecutive patients who underwent curative surgery for stage II CRC between January 2001 and December 2006. Of these, 278 patients (81.5%) received postoperative 5-fluorouracil-based chemotherapy. The oncologic outcomes and the risk factors for recurrence were analyzed. RESULTS: PNI was detected in 57 of 341 patients (16.7%) and was significantly associated with depth of tumor invasion (P = .035) and positive lymphovascular invasion (P < .001). Multivariate analyses revealed that PNI was a significant independent prognostic factor for disease-free survival, not for overall survival. With a median follow-up period of 57.6 months, the 5-year disease-free and overall survival rates of the patients were 80.2 and 82.6%, respectively. The 5-year disease-free survival of the PNI-negative group was significantly higher than that of the PNI-positive group (P < .001). Within the PNI-positive patients, those receiving chemotherapy had significantly higher 5-year disease-free survival than the others (P = .023). CONCLUSION: This study illustrates the value of PNI as a prognostic factor for stage II CRC. Moreover, PNI-positive patients should be considered for postoperative chemotherapy.

Postoperative chemotherapy after neoadjuvant chemoradiation and surgery for rectal cancer: is it essential for patients with ypT0-2N0?

BACKGROUND: The potential advantage of adjuvant chemotherapy in patients with ypT0-2N0 rectal cancer remains unclear. The purpose of this study was to evaluate whether this therapy has an impact on survival. MATERIALS AND METHODS: Patients who underwent curative surgery after preoperative chemoradiation for locally advanced low rectal cancer were retrospectively reviewed. A total of 41 consecutive patients with pathological stage 0 (ypT0N0) or I (ypT1-2N0) were enrolled. Of the 41 patients, 17 (41.5%) received postoperative 5-fluorouracil (5-FU)-based chemotherapy, while 24 were followed without postoperative therapy. Oncologic outcomes were compared between the two groups. RESULTS: The median follow-up period was 47.6 months. The overall postoperative complication rates did not differ significantly between the patients who received chemotherapy and those who did not (17.6% vs. 20.8%, P = 0.799). The 5-year overall and disease-free survival rates for patients who received chemotherapy were 88.9% and 84.7%, which were not significantly different from the rates for those who did not (85.9%; P = 0.644 and 73.4%; P = 0.599, respectively). CONCLUSIONS: Postoperative adjuvant chemotherapy for patients with good responses after preoperative chemoradiation and curative surgery did not significantly improve the survival. However, this should be validated in prospective randomized trials with larger sample sizes.