Impact of Preoperative Immunonutrition on the Outcomes of Colon Cancer Surgery: Results from a Randomized Controlled Trial.

OBJECTIVE: This study aimed to assess the impact of preoperative immunonutrition on the outcomes of colon cancer surgery. BACKGROUND: Although current guidelines recommend that immunonutrition should be prescribed for malnourished patients before major gastrointestinal surgery, the benefit of preoperative immunonutrition remains debatable. METHODS: Between April 2019 and October 2020, 176 patients with primary colon cancer were enrolled and randomly assigned (1:1) to receive preoperative immunonutrition plus a normal diet (n = 88) or a normal diet alone (n = 88). Patients in the immunonutrition group received oral nutritional supplementation (400 mL/d) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint was the rate of infectious complications, and the secondary endpoints were the postoperative complication rate, change in body weight, and length of hospital stay. RESULTS: The rates of infectious (17.7% vs 15.9%, P = 0.751) and total (31.6% vs 29.3%, P = 0.743) complications were not different between the two groups. Old age was the only significant predictive factor for the occurrence of infectious complications (odds ratio = 2.990, 95% confidence interval 1.179-7.586, P = 0.021). The length of hospital stay (7.6 ± 2.5 vs 7.4 ± 2.3 days, P = 0.635) and overall change in body weight ( P = 0.379) were similar between the two groups. However, only the immunonutrition group showed weight recovery after discharge (+0.4 ± 2.1 vs -0.7 ± 2.3 kg, P = 0.002). CONCLUSIONS: Preoperative immunonutrition was not associated with infectious complications in patients undergoing colon cancer surgery. Routine administration of immunonutrition before colon cancer surgery cannot be justified.

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.

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Periumbilical Transverse Incision for Reducing Incisional Hernia in Laparoscopic Colon Cancer Surgery.

BACKGROUND: Although off-midline incisions (unilateral low transverse or Pfannenstiel incision) have been reported to have a lower incidence of incisional hernia (IH) than periumbilical vertical incision for the purpose of specimen extraction, it is most commonly used in laparoscopic colon cancer surgery because off-midline incisions are associated with the limitation of colon exteriorization. This study aims to investigate the risk of IH after laparoscopic colectomy and compare midline vertical incision versus transverse incision focusing on the incidence of IH. METHODS: Patients who underwent elective laparoscopic colectomy due to colon malignancy from June 2015 to May 2017 were included. All patients had either vertical (n = 429) or muscle splitting periumbilical transverse incisions (n = 125). RESULTS: Median duration of the follow-up period was 23.6 months, during which IHs occurred in 12.1% patients. The incidence of hernia was significantly lower in the transverse group (3 vs. 64, 2.4% vs. 14.9%, p < 0.001). On multivariate analysis, BMI ≥ 23 [odds ratio (OR) 2.282, 95% confidence interval (CI) 1.245-4.182, p = 0.008], postoperative surgical site infection (OR 3.780, 95% CI 1.969-7.254, p < 0.001) and vertical incision (OR 7.113, 95% CI 2.173-23.287, p < 0.001) were independently related with increased incidence of IH. CONCLUSIONS: A muscle splitting periumbilical transverse incision could significantly reduce the rate of IH in minimally invasive colon cancer surgery.

Effect of the First Assistant on Anastomotic Leakage after Rectal Cancer Surgery with Double-Stapling Anastomosis: A Propensity Score Matching Analysis.

INTRODUCTION: Proper handling and firing of the circular stapler are important for secure anastomosis in rectal cancer surgery. This study aimed to investigate the association between the first assistant and anastomotic leakage (AL) after rectal cancer surgery with double-stapling anastomosis. METHODS: Patients with primary rectal cancer who underwent low anterior resection with double-stapling anastomosis between January 2015 and September 2019 were included. Data on clinicopathological characteristics, including the first assistant's sex and experience level, were retrospectively reviewed, and the risk factors for AL were analyzed using propensity score matching analysis. RESULTS: Among 758 rectal cancer surgeries, residents participated in 401 (52.9%) surgeries, and fellows participated in 357 (47.1%) surgeries as first assistants. After propensity score matching (n = 650), AL occurred in 5.4% (35/650). The first assistant's experience level (resident: 5.5% vs. fellow: 5.2%, p = 0.862) and sex (male: 5.4% vs. female: 4.9%, p = 0.849) were not associated with the occurrence of AL. Male sex in patients was the only significant predictive factor for AL (odds ratio = 2.804, 95% confidence interval 1.070-7.351, p = 0.036). DISCUSSION/CONCLUSION: The first assistant's sex and experience level were not associated with AL after rectal cancer surgery with double-stapling anastomosis. These findings may justify resident participation in rectal cancer surgeries in which circular staplers are used.

Proper surgical extent for clinical Stage I right colon cancer.

PURPOSE: Pre-operative evaluation identifying clinical-stage affects the decision regarding the extent of surgical resection in right colon cancer. This study was designed to predict a proper surgical resection through the prognosis of clinical Stage I right colon cancer. PATIENTS AND METHODS: We included patients who were diagnosed with clinical and pathological Stage I right-sided colon cancer, including appendiceal, caecal, ascending, hepatic flexure and proximal transverse colon cancer, between August 2010 and December 2016 in two tertiary teaching hospitals. Patients who underwent open surgeries were excluded because laparoscopic surgery is the initial approach for colorectal cancer in our institutions. RESULTS: Eighty patients with clinical Stage I and 104 patients with pathological Stage I were included in the study. The biopsy reports showed that the tumour size was larger in the clinical Stage I group than in the pathological Stage I group (3.4 vs. 2.3 cm, P < 0.001). Further, the clinical Stage I group had some pathological Stage III cases (positive lymph nodes, P = 0.023). The clinical Stage I group had a higher rate of distant metastases (P = 0.046) and a lower rate of overall (P = 0.031) and cancer-specific survival (P = 0.021) than the pathological Stage I group. Compared to pathological Stage II included in the period, some of the survival curves were located below the pathological Stage II, but there was no statistical difference. CONCLUSION: The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Distribution of lymph node metastasis and oncological outcomes of mid-transverse colon cancer: extended versus transverse colectomy.

AIM: The optimal surgical method for cancer of the mid-transverse colon has not been well established. The present study aimed to explore the distribution of lymph node metastasis and compare the outcomes of extended and transverse colectomies for cancer of the mid-transverse colon. METHODS: We retrospectively analysed the data of patients with cancer of the mid-transverse colon treated with either an extended hemicolectomy (right or left) or a transverse colectomy. A propensity score matching analysis was performed to rule out selection bias, and short-term and survival outcomes were compared. The distribution of lymph node metastasis was also investigated. RESULTS: A total of 107 patients were included, 70 of whom underwent an extended colectomy while 37 underwent a transverse colectomy. There were no significant differences in the operation time, postoperative complications, hospital stay, 3-year disease-free survival (86.5% vs. 90.9%, P = 0.675) and 5-year overall survival (87.4% vs. 93.0%, P = 0.349) between the two groups after propensity score matching. However, metastases were observed in the lymph nodes along the right colic artery (pericolic [#211], 14.0%; intermediate [#212], 8.2%; apical [#213], 9.8%) in the extended colectomy group. CONCLUSION: Extended and transverse colectomies showed similar short-term and long-term outcomes for mid-transverse colon cancer. However, care should be taken to determine the extent of resection considering the possibility of metastatic lymph nodes along the right colic artery.

Perineural invasion and number of retrieved lymph nodes are prognostic factors for T2N0 colon cancer.

PURPOSE: The prognosis of pathological T2N0 colon cancer has not been adequately investigated. This study aimed to determine the prognostic factors for pathological T2N0 colon cancer by comparing it with those for pathological T3N0 colon cancer. METHODS: We retrospectively reviewed patients with primary colon cancer who underwent curative resection between January 2007 and December 2015 and included 889 patients with postoperative pathological T2-3N0M0 disease. The clinicopathological characteristics were analyzed to identify the independent prognostic factors. RESULTS: Pathological T2 (n = 185, 20.8%) and T3 (n = 704, 79.2%) tumors showed no difference in the 5-year disease-free survival (5Y DFS) rate (95.8% vs. 93.2%, p = 0.257) after a median follow-up of 55 months (range, 1-106 months). Multivariate Cox regression analysis showed that perineural invasion (hazard ratio [HR] = 2.041, 95% confidence interval [CI] 1.122-3.712, p = 0.019) and number of retrieved lymph nodes < 12 (HR = 2.994, 95% CI 1.327-6.753, p = 0.008) were independent prognostic factors for DFS. Pathological T2 tumors with poor prognostic factors showed similar 5Y DFS as that of T3 tumors with poor prognostic factors (88.9% vs. 88.6%, p = 0.916), but not with T3 tumors without poor prognostic factors (88.9% vs. 95.0%, p = 0.089). CONCLUSION: Pathological T2N0 colon cancer showed oncologic outcomes similar to that of T3N0 colon cancer. Therefore, more intensive surveillance is necessary for patients with high-risk T2N0 colon cancer.

Prognostic significance of enlarged paraaortic lymph nodes detected during left-sided colorectal cancer surgery: a single-center retrospective cohort study.

BACKGROUND: Very few studies have been conducted on the treatment strategy for enlarged paraaortic lymph nodes (PALNs) incidentally detected during surgery. The purpose of this study was to investigate the benefit of lymph node dissection in patients with incidentally detected enlarged PALNs. METHODS: We retrospectively reviewed patients with left colon and rectal cancer who underwent surgical resection with PALN dissection between January 2010 and December 2018. The predictive factors for pathologic PALN metastasis (PALNM) were analyzed, and survival analyses were conducted to identify prognostic factors. RESULTS: Among 263 patients included, 19 (7.2%) showed pathologic PALNM and 5 (26.33%) had enlarged PALNs incidentally detected during surgery. These 5 patients accounted for 2.2% of 227 patients who had no evidence of PALNM on preoperative radiologic examination. Radiologic PALNM (odds ratio [OR] 12.737, 95% confidence interval [CI] 3.472-46.723) and radiologic distant metastasis other than PALNM (OR = 4.090, 95% CI 1.011-16.539) were independent predictive factors for pathologic PALNM. Pathologic T4 stage (hazard ratio [HR] 2.196, 95% CI 1.063-4.538) and R2 resection (HR 4.643, 95% CI 2.046-10.534) were independent prognostic factors for overall survival (OS). In patients undergoing R0 resection, pathologic PALNM was not associated with 5-year OS (90% vs. 82.2%, p = 0.896). CONCLUSION: Dissection of enlarged PALNs incidentally detected during colorectal surgery may benefit patients with favorable survival outcomes.

Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer.

Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross-talk between FGFR4 and EGFR, and the effect of anti-EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab-induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti-EGFR therapy in colon cancer.

Impact of Family History on Prognosis of Patients with Sporadic Colorectal Cancer.

PURPOSE: A family history (FH) of colorectal cancer (CRC) increases the risk for development of CRC, but the impact of FH of CRC on survival from sporadic CRC is unclear. This study investigated the prognostic impact of FH of CRC on the recurrence and survival of patients with sporadic CRC. METHODS: We reviewed the records of patients with sporadic CRC from two tertiary referral hospitals in Korea who underwent surgical resection between May 2007 and September 2013. The clinicopathologic features and oncologic outcomes of those with and without FHs of CRC were compared. RESULTS: We examined the records of 2960 eligible patients, 163 (5.5%) of whom had first-degree relatives with CRC. Patients with and without FHs of CRC had similar baseline characteristics. Multivariable analysis indicated that a FH of CRC was not significantly associated with disease-free survival but was significantly associated with better overall survival (OS) [adjusted hazard ratio = 0.539, 95% confidence interval (CI) 0.330-0.881, P = 0.014]. Subgroup analysis indicated that females and rectal cancer patients with FHs of CRC had significantly better prognoses. Microsatellite status did not affect the improved survival rate associated with FH. CONCLUSIONS: This study of patients with sporadic CRC indicated that those who had FHs of CRC had better OS but similar cancer recurrence as those who had no FH of CRC. The effect of FH of CRC on OS was independent of microsatellite status. Further studies are needed to identify underlying mechanisms and determine the optimal clinical management of CRC according to FH.

The prognostic effect of adjuvant chemotherapy in the colon cancer patients with solitary lymph node metastasis.

PURPOSE: Previous studies have reported paradoxical survival prognoses for some node-negative and node-positive colon cancer patients. However, current guidelines recommend adjuvant chemotherapy (CT) only for node-positive patients. This study investigated the efficacy of adjuvant CT for patients who underwent radical surgery for colon cancer with solitary lymph node (LN) metastasis. METHODS: This study included 281 patients treated between 2004 and 2015. Patients were classified into no-CT (n = 39) and CT (n = 242) groups, and the survival outcomes and recurrence-related follow-up data were analyzed. RESULTS: The groups exhibited similarities in tumor sidedness, tumor differentiation, and pathologic stage. However, the age, ASA class, and preoperative CEA level were relatively lower in the CT group. Although the CT group had a higher 5-year overall survival (OS) rate than the no-CT group (88.4% vs. 65.3%, p < 0.001), the groups did not differ in terms of 5-year disease-free survival (DFS) (CT, 84.1% vs. no-CT, 83.3%, p = 0.490). A multivariate analysis identified adjuvant CT as an independent factor for OS but not for DFS. A highly examined LN count (≥ 12) was associated with improved DFS improvement. However, D3 LN dissection was not associated with DFS or OS. For DFS, intermediate/apical positive LNs received a high hazard ratio relative to pericolic/epicolic LNs (2.080, 95% confidence interval: 0.979-4.416), but this was not significant (p = 0.057). CONCLUSIONS: Adjuvant chemotherapy did not provide clear advantages for colon cancer with solitary LN metastasis. Further large studies that analyze several prognostic factors are needed to establish tailored adjuvant CT administration guidelines.

The relation between oncologic outcomes and metastatic lymph node location following laparoscopic resection of stage III colon cancer.

PURPOSE: Colon cancers are staged by assessing more than 12 lymph nodes, but there is still a controversy over the number of lymph nodes. Only a few studies of metastatic lymph node position in colon cancer have been published with its significance not completely understood. This study aimed to compare survival rates according to metastatic lymph node position following radical lymph node dissection for stage III colon cancers. METHODS: This retrospective study evaluated data prospectively collected at a tertiary teaching hospital from 349 patients who underwent laparoscopic colectomy with radical node dissection between December 2009 and December 2014. Lymph nodes were numbered and classified into lymph node metastasis (LNM) groups LNM1, LNM2, and LNM3 and their short- and long-term outcomes were compared. RESULTS: The LNM1, LNM2, and LNM3 groups included 229, 94, and 26 patients, respectively. Patient characteristics differed by locations (p < 0.001). A mean 34.6 lymph nodes were harvested, and a mean 2.6, 5, and 9 metastatic nodes were identified, respectively (p < 0.001), a finding that is proportional to the cancer stage (tau-b = 0.284, p < 0.001; rho = 0.3, p < 0.001). The 5-year disease-free survival rate did not differ among the three groups; however, the LNM3 group had the poorest overall and cancer-specific survival rates. Risk factors associated with cancer-specific survival rate were identified with neural invasion, poorly differentiated tumors, and the location of pathologic lymph nodes (LNM). CONCLUSION: Metastatic lymph node location affects oncologic outcomes of stage III colon cancer. The patients for LNM3 metastasis should receive a more aggressive adjuvant treatment.

Prognostic Impact of Perineural Invasion in Rectal Cancer After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Perineural invasion (PNI) has emerged as an important factor related to colorectal cancer spread; however, the impact of neoadjuvant chemoradiotherapy (nCRT) on PNI remains unclear. Herein, we investigated the prognostic value of PNI, along with lymphovascular invasion (LVI), in rectal cancer patients treated with nCRT. METHODS: This single-center observational study of pathologic variables, including PNI and LVI, analyzed 1411 invasive rectal cancer patients (965 and 446 patients treated with primary resection and nCRT, respectively). RESULTS: The overall detection rates of LVI and PNI were 16.7 and 28.8%, respectively. The incidence of LVI was significantly lower in patients treated with nCRT (8.1 vs. 20.6%, P < .001); this was confirmed by multivariate analysis. However, PNI was not affected by nCRT (with nCRT 28.3% vs. without nCRT 29.1%, P = .786). In the 446 patients with nCRT, multivariate analysis revealed that PNI was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS). For the prediction of both 5-year DFS and OS, the C-index for the combinations of T-stage with the PNI (TPNI) system showed favorable result, especially in patients with a total number of harvested lymph nodes <8. CONCLUSION: PNI is a meaningful prognostic factor for rectal cancer patients treated with nCRT, especially when <8 lymph nodes are harvested. The lack of influence of nCRT on the PNI incidence suggests that residual tumor cells with PNI are more radioresistant or biologically aggressive than those without.

Prognostic significance of the distribution of lymph node metastasis in rectal cancer after neoadjuvant chemoradiation.

BACKGROUND: This study aimed to evaluate the prognostic significance of lymph node distribution (LND) in rectal cancer after neoadjuvant chemoradiation. METHODS: A total of 519 patients with primary rectal cancer who underwent curative resection after neoadjuvant chemoradiation were included. LND was classified into four groups: LND0, no lymph node metastasis (368/519, 70.9%); LNDp, lymph node metastasis along the inferior mesenteric artery (proximal) (15/519, 2.9%); LNDm, lymph node metastasis at the mesorectum (109/519, 21.0%); and LNDpm, lymph node metastasis at both the proximal and mesorectal areas (27/519, 5.2%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. RESULTS: In patients with positive lymph nodes, LND showed superior discrimination for 3-year DFS (LNDp 67.7%, LNDm 48.9%, and LNDpm 26.8%, P = 0.003) and 3-year LRFS (LNDp 93.3%, LNDm 81.4%, and LNDpm 60.5%, P = 0.009) compared to ypN stage (3-year DFS, N1 47.8%, N2 40.0%, P = 0.184; 3-year LRFS, N1 79.4%, N2 75.2%, P = 0.527). On multivariate survival analysis, LND was an independent prognostic factor for LRFS (P = 0.030) in patients with positive lymph nodes. CONCLUSIONS: LND may improve the prognostic value of the ypTNM staging system for patients with node-positive rectal cancer after neoadjuvant chemoradiation, particularly in terms of local recurrence.

Macroscopic serosal invasion and small tumor size as independent prognostic factors in stage IIA colon cancer.

BACKGROUND: This study aimed to investigate the prognostic factors of patients with stage IIA (T3N0M0) colon cancer in terms of macroscopic serosal invasion and small tumor size. METHODS: We enrolled 375 stage IIA colon cancer patients who underwent curative resection between January 2004 and December 2011. Macroscopic serosal invasion was defined as tumor nodules or colloid changes protruding the surface of the serosa. The clinicopathologic characteristics were analyzed to identify independent prognostic factors. RESULTS: The median follow-up was 47 months (range, 1-90 months). On multivariate survival analysis, macroscopic serosal invasion (adjusted hazard ratio [HR] = 4.750; p = 0.013), tumor size < 5 cm (adjusted HR = 3.112, p = 0.009), perineural invasion (adjusted HR = 3.528; p = 0.002), < 12 retrieved lymph nodes (adjusted HR = 4.257; p = 0.002), and localized perforation (adjusted HR = 7.666; p = 0.008) were independent risk factors for recurrence. CONCLUSION: We found novel prognostic factors of stage IIA colon cancer, including macroscopic serosal invasion and small tumor size (< 5 cm). Further studies are needed to evaluate the benefit of adjuvant chemotherapy in patients with these prognostic factors.

Anastomotic stricture after ultralow anterior resection or intersphincteric resection for very low-lying rectal cancer.

BACKGROUND: Anastomotic stricture following colorectal cancer surgery is not a rare complication, but proper management of anastomotic stricture located close to the anal verge is uncertain. This study aimed to investigate risk factors and management strategies for anastomotic stricture after ultralow anterior resection (ULAR). METHODS: We retrospectively reviewed a database of patients with rectal cancer who underwent surgery between January 2007 and June 2015, and included patients with an anastomosis within 4 cm from the anal verge. Clinical outcomes and risk factors for anastomotic stricture were investigated. RESULTS: Among the 586 patients included, 46 (7.8%) were diagnosed as having anastomotic stricture. Multivariable logistic regression analysis revealed that intersphincteric resection (ISR) with hand-sewn anastomosis (odds ratio [OR] = 3.070; 95% confidence interval [CI] 1.247-7.557) and postoperative radiotherapy (OR 6.237; 95% CI 1.961-19.841) were independent risk factors of anastomotic stricture. Forty-one (89.1%) underwent anastomotic dilatation with a Hegar dilator; while three patients (6.5%) underwent endoscopic balloon dilatation and two (4.3%) underwent surgery initially. Among the patients with initial nonoperative management (n = 44), 21 (47.7%) were completely cured with nonoperative management alone, 12 (27.3%) experienced complications, such as bowel perforation, anastomotic rupture, and perirectal abscess; and 21 (47.7%) underwent further surgical management. Fifteen patients (32.6%) eventually had permanent stoma. CONCLUSION: ISR with a hand-sewn coloanal anastomosis, compared to ULAR with double-stapling anastomosis, and postoperative radiotherapy were independent risk factors of anastomotic stricture after surgery for very low-lying rectal cancer. Nonoperative anastomotic dilatation showed poor clinical outcome, with high complication rates, and subsequent surgical management. Therefore, nonoperative management of such patients should be carefully selected.

Intracorporeal Traction of the Rectum with a Beaded Plastic Urinary Drainage Bag Hanger: Comparison with Conventional Laparoscopic Rectal Cancer Surgery.

BACKGROUND: Laparoscopic rectal cancer surgery with proper total mesorectal excision is a challenge for colorectal surgeons during trouble shooting. We used a beaded plastic urinary drainage bag hanger to encircle the rectum and clamp laparoscopic rectal transaction in this study. METHODS: Sixty-three patients with rectal cancer underwent laparoscopic radical rectal resection with curative intent between February 2015 and December 2015. Plastic beaded form urinary Foley catheter bag hanger was inserted intracorporeally via right lower 12-mm trocar, encircling the rectal tube distal to the rectal lesion followed by fastening. Thirty patients in the rectal resection group (28 laparoscopic, 2 robotic-assisted) using the commercial beaded plastic hanger for Foley catheter drainage were compared to 33 patients who underwent conventional laparoscopic rectal resection. RESULTS: Low anterior resection was performed for both groups. The Foley bag hanger group had less operation time (162.6 min vs. 187.3 min, p = 0.006) and fewer numbers of stapler cartilage (1.6 vs. 2.1, p = 0.001). CONCLUSIONS: Intracorporeal ligation of the rectum with a beaded plastic Foley catheter bag hanger could be used as a valuable method for rectal handling and transaction in laparoscopic rectal cancer surgery.

Microsatellite Alterations With Allelic Loss at 9p24.2 Signify Less-Aggressive Colorectal Cancer Metastasis.

BACKGROUND & AIMS: Molecular events that lead to recurrence and/or metastasis after curative treatment of patients with colorectal cancers (CRCs) are poorly understood. Patients with stage II or III primary CRC with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability (E/L) are more likely to have disease recurrence after treatment. Hypoxia and/or inflammation not only promote metastasis, but also induce elevated microsatellite alterations at selected tetranucleotide repeats by causing deficiency of MSH3 in the cancer cell nucleus. We aimed to identify genetic alterations associated with metastasis of primary colorectal tumors to liver and to determine their effects on survival. METHODS: We obtained 4 sets of primary colorectal tumors and matched liver metastases from hospitals in Korea and Japan. Intragenic microsatellites with large repeats at 141 loci were examined for frame-shift mutations and/or loss of heterozygosity (LOH) as possible consequences of MSH3 deficiency. Highly altered loci were examined for association with E/L in liver metastases. We analyzed data from 156 of the patients with stage II or III primary colorectal tumors to determine outcomes and whether altered loci were associated with E/L. RESULTS: LOH at several loci at chromosome 9p24.2 (9p24.2-LOH) was associated with E/L in liver metastases (odds ratio = 10.5; 95% confidence interval: 2.69-40.80; P = .0007). We found no significant difference in the frequency of E/L, 9p24.2-LOH, mutations in KRAS or BRAF, or the combination of E/L and 9p24.2-LOH, between primary colorectal tumors and their matched metastases. Patients with stage II or III colorectal tumors with E/L and 9p24.2-LOH had increased survival after CRC recurrence (hazard ratio = 0.25; 95% CI: 0.12-0.50; P = .0001), compared with patients without with E/L and 9p24.2-LOH. E/L with 9p24.2-LOH appeared to be an independent prognostic factor for overall survival of patients with stage III CRC (hazard ratio = 0.06; 95% CI: 0.01-0.57; P = .01). CONCLUSIONS: E/L with 9p24-LOH appears to be a biomarker for less aggressive metastasis from stage III primary colorectal tumors.