Sung Bum Kang

Multicenter Analysis of Risk Factors for Anastomotic Leakage After Laparoscopic Rectal Cancer Excision The Korean Laparoscopic Colorectal Surgery Study Group

Objective:To assess the risk factors for clinical anastomotic leakage (AL) in patients undergoing laparoscopic surgery for rectal cancer. Background:Little data are available about risk factors for AL after laparoscopic rectal cancer resection. Methods:This was a retrospective analysis of 1609 patients with rectal cancer who had undergone laparoscopic surgery for rectal cancer with sphincter preservation. Clinical data related to AL were collected from 11 institutions. Univariate and multivariate analyses were performed to determine the risk factors for AL. Results:AL was noted in 101 (6.3%) of the patients. The leakage rate ranged from 2.0% to 10.3% for each hospital (P = 0.04). In patients without protective stomas (n = 1187), male sex [hazard ratio (HR), 3.468], advanced tumor stage (HR, 2.520), lower tumor level (HR, 2.418), preoperative chemoradiation (HR, 6.284), perioperative transfusion (HR, 10.705), and multiple firings of the linear stapler (HR, 6.181) were significantly associated with AL. Our theoretical model suggested that the HR for patients with 2 risk factors was significantly higher than that the HR for patients with no or only 1 risk factor. Conclusions:Male sex, low anastomosis, preoperative chemoradiation, advanced tumor stage, perioperative bleeding, and multiple firings of the linear stapler increased the risk of AL after laparoscopic surgery for rectal cancer. A diverting stoma might be mandatory in patients with 2 or more of the risk factors identified in this analysis.

Comparative study of NOTES rectosigmoidectomy in a swine model: E-NOTES vs. P-NOTES.

BACKGROUND AND STUDY AIMS Several reports have demonstrated the safety of pure natural-orifice transluminal endoscopic surgery (P-NOTES) using transanal endoscopic microsurgery (TEM) and embryonic NOTES (E-NOTES; laparoscopic surgery through the umbilicus). This study was performed to compare the safety and applicability of NOTES rectosigmoidectomy between E-NOTES and P-NOTES in a swine model. PATIENTS AND METHODS E-NOTES was conducted through a single port using laparoscopic instruments (n = 11). P-NOTES was performed using TEM with transgastric endoscopic assistance (n = 11). Gastrotomies were created using a needle knife and the balloon dilatation technique, and closed using T-anchors. Blood samples were collected to evaluate changes in systemic cytokine levels during the preoperative and postoperative periods; operative outcomes were also evaluated and compared between the groups. The necropsy findings were recorded after sacrifice at 1 week after the procedure. RESULTS The mean operative time for P-NOTES was significantly longer than that for E-NOTES (239 vs. 103 minutes, P < 0.001). The mean distance from the anal verge to colorectal anastomosis in the P-NOTES group was significantly less than that in the E-NOTES group (2.9 vs. 17.6 cm, P < 0.001). On necropsy, the complication rate of P-NOTES was higher than that of E-NOTES, but without statistical significance (54.5 % vs. 18.2 %, P = 0.091). The differences in changes in TNF-α, C-reactive protein, interleukin-6, and interleukin-1β between P-NOTES and E-NOTES were not significant. CONCLUSIONS E-NOTES rectosigmoidectomy in the swine model is safe, but remains challenging for use in pelvic dissection. P-NOTES rectosigmoidectomy using TEM may be a promising tool for pelvic dissection, but the transgastric approach involves a high degree of risk.

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer.

Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC.

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.

Investigation of Clinical Manifestations in Korean Colorectal Cancer Patients

Purpose Early diagnostic work-up in patients with clinical symptoms of colorectal cancer (CRC) is important to achieve good treatment results. In this study, we investigated clinical symptoms when a diagnosis of CRC was made in patients who had a surgical resection, especially focusing on the relevance of constipation to CRC. Methods The clinical symptoms of 17,415 CRC patients who had curative surgery from January 2010 to December 2012 were collected from 24 training hospitals of surgery. Results The number of symptomatic patients before the diagnosis of CRC was 11,085 (63.7%). Hematochezia or melena, abdominal pain, anemia, and constipation were more often found in female than male patients while bowel habit change was more common in male patients. Considering age, bowel habit change and hematochezia or melena were more common in patients younger than 60. Anemia and constipation, however, were more common in patients older than 60. According to the group classification based on age, patients older than 60 had experienced more constipation (P = 0.049). Moreover, patients with constipation tended to have a more advanced disease status (P < 0.001). Conclusion In patients who had surgery due to CRC, bleeding, abdominal pain, bowel habit change and constipation were the most frequent symptoms before diagnosis. Although whether or not constipation is a cause of CRC is unclear, it is one of the important clinical symptoms that presents in patients with CRC, and patients with a symptom of constipation tend to present with a more advanced CRC stage.

Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry (ROTEM® ).

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg−1 followed by a continuous infusion of 15 mg.kg−1.h−1), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l−1 in the magnesium group compared with 0.98 (0.06) mmol.l−1 in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra‐operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery.

Effects of depth of neuromuscular block on surgical conditions during laparoscopic colorectal surgery: a randomised controlled trial

There have been few objective evaluations of the effects of deep neuromuscular blockade on intra‐operative conditions. In this prospective randomised controlled study, we evaluated the effects of deep neuromuscular block on surgical conditions during laparoscopic colorectal surgery. Patients were randomly allocated using a computer‐generated randomisation code to either moderate (train‐of‐four count 1–2 maintained and antagonised with neostigmine) or deep (post‐tetanic count 1–2 maintained and reversed with sugammadex) levels of neuromuscular blockade. The primary outcome measure was the number of abrupt increases in intra‐abdominal pressure intra‐operatively. Secondary outcome variables were intra‐operative restoration of spontaneous breathing, number of surgical requests for additional neuromuscular blockade, surgical rating of operating conditions and patient satisfaction. The surgeon who rated the surgical conditions score and investigator who checked the postoperative variables were blinded to patient allocation. In total, we recruited 70 patients of whom 64 (32 in each group) were analysed. Increases in intra‐abdominal pressure (14/32 vs. 6/32; p = 0.031), intra‐operative restoration of spontaneous breathing (16/32 vs. 2/32; p < 0.001) and request for additional neuromuscular blockade (21/32 vs. 8/32; p = 0.001) were more frequent in the moderate compared with the deep group. In patients undergoing elective laparoscopic colorectal surgery, deep neuromuscular blockade provided better surgical conditions than moderate neuromuscular blockade, as measured by a reduction in the incidence of intra‐abdominal pressure alarms.

Adjuvant radiotherapy for the treatment of stage IV rectal cancer after curative resection: A propensity score-matched analysis and meta-analysis

AbstractThe role of pelvic radiotherapy (RT) in stage IV rectal cancer with total mesorectal excision (TME) has not been defined. We evaluated the impact of RT on oncologic outcomes among patients with stage IV rectal cancer who underwent TME and performed a meta-analysis of published studies.The records of stage IV rectal cancer patients who underwent TME between August 2001 and December 2011 were reviewed. Patients who received pelvic RT (RT group) and those who did not (non-RT group) were matched using a propensity score. Oncologic outcomes were compared between the groups. A systematic literature search and meta-analysis was conducted.One hundred seventy-six patients were matched with propensity score matching, resulting in 39 patients in each group. The local recurrence-free survival (LRFS) of the RT group was significantly higher than that of the non-RT group (2-year LRFS: 100% vs 83.6%, respectively, P = 0.038). The overall survival, disease-free survival, and systemic recurrence were not significantly different between the groups. In the meta-analysis, the RT group had a reduced risk for loco-regional recurrence than the non-RT group (RR: 0.48, 95% confidence interval: 0.29–0.79).Pelvic RT might have benefits for loco-regional control in patients with stage IV rectal cancer who undergo TME.

Surgical site infection after colorectal surgery according to the main anesthetic agent: a retrospective comparison between volatile anesthetics and propofol.

Background Anesthetic agents used for general anesthesia are emerging possible influential factors for surgical site infection (SSI). In this retrospective study, we evaluated the incidence of SSI after colorectal surgery according to the main anesthetic agents: volatile anesthetics vs. propofol. Methods A total 1,934 adult patients, who underwent elective colorectal surgery under general anesthesia between January 2011 and December 2013, were surveyed to evaluate the incidence of SSI: 1,519 using volatile anesthetics and 415 using propofol for main anesthetic agents. Patient, surgery, and anesthesia-related factors were investigated from all patients. Propensity-score matching was performed to reduce the risk of confounding and produced 390 patients in each group. Results Within the propensity-score matched groups, the incidence of SSI was higher in the volatile group compared with the propofol group (10 [2.6%] vs. 2 [0.5%], OR = 5.0 [95% CI = 1.1-2.8]). C-reactive protein was higher in the volatile group than in the propofol group (8.4 ± 5.6 vs. 7.1 ± 5.3 mg/dl, P = 0.001), and postoperative white blood cells count was higher in the volatile group than in the propofol group (9.2 ± 3.2 × 103/µl vs. 8.6 ± 3.4 × 103/µl, P = 0.041). Conclusions The results of this study suggest that intravenous anesthesia may have beneficial effects for reducing SSI in colorectal surgery compared to volatile anesthesia.

Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancer

BackgroundThe purpose of this study was to explore gene copy number (GCN) variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal cancer (CRC).MethodsDual-colour silver-enhanced in situ hybridization was performed in tissue samples of 334 primary CRC patients. The amplification status (GCN ratio ≥2) and GCN gain (average GCN ≥4) data for the EGFR, HER2, c-MYC and MET genes were obtained. GCN variation was also assessed by the criterion of the 2013 ASCO/CAP guidelines for HER2 testing.ResultsAmplification of EGFR, HER2, c-MYC and MET was detected in 8 (2.4%), 20 (6.0%), 29 (8.7%), and 14 (4.2%) patients, respectively. Of 66 patients with at least one amplified gene, five exhibited co-amplification of genes studied (HER2-MET co-amplification: two patients; HER2-c-MYC co-amplification: two patients; EGFR-c-MYC co-amplification: one patient). There were 109 patients with GCN gains of one or more genes (EGFR: 11/334, HER2: 29/334, c-MYC; 60/334, MET: 48/334) and 32.1% (35/109) had multiple GCN gains. When each GCN was assessed by the criterion of the ASCO/CAP 2013 guideline for HER2 testing, 116 people showed positive or equivocal results for one or more genes. The cumulative amplification status had no association with patients’ outcome. However, the cumulative results of the GCN gain and GCN status determined according to the ASCO/CAP guideline had a significant prognostic correlation in the univariate analysis (P values of 0.006 and 0.022, respectively). In the multivariate analysis, GCN gain and GCN status were independent prognostic factors (P values of 0.010 and 0.017, respectively).ConclusionsIn this study, we evaluated GCN variation of four genes in a large sample of Korean CRC patients. The amplification status was not related to patient outcome. However, the GCN gain and GCN status according to the ASCO/CAP 2013 guideline were independent prognostic factors.