Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional analysis in an Asian population.

PURPOSE: This study was conducted to evaluate the significance of carcinoembryonic antigen (CEA) level as a predictor for tumor response to chemoradiotherapy (CRT) and a prognosticator for survival in Asian patients with advanced rectal cancer. MATERIALS AND METHODS: We enrolled 345 patients with primary rectal cancer who had undergone preoperative CRT and total mesorectal excision. We analyzed clinicopathological factors that could be associated with pathologically complete response (ypCR) and disease-free survival (DFS). RESULTS: A cutoff level of 5 ng/mL (p = 0.002) for CEA was found to be significant for prediction of ypCR. Increased CEA level (p = 0.025) was a significant negative predictor of ypCR after CRT in patients with rectal cancer. The 5-year DFS rate was significantly higher in the CEA ≤5-ng/mL group than in the CEA >5-ng/mL group (73.2 vs. 60.9 %, p = 0.002). This is mainly due to the higher chance of distant recurrence (p = 0.013), not locoregional recurrence (p = 0.732), in the CEA >5-ng/mL group. CONCLUSIONS: Elevated CEA (>5 ng/mL) is a negative predictor of ypCR and has a negative impact on DFS in Asian rectal cancer patients who underwent preoperative CRT and surgery due to an increased chance of distant recurrences.

Endoscopic submucosal dissection for colorectal tumors--1,000 colorectal ESD cases: one specialized institute's experiences.

PURPOSE: Endoscopic submucosal dissection (ESD) is a very useful endoscopic technique, making it possible to perform en bloc resection regardless of lesion size. Since the introduction of ESD at our hospital, we have performed 1,000 colorectal ESDs during 56 months. The purpose of this study was to evaluate the clinical outcomes of our colorectal ESD experience and to access the efficacy and safety of colorectal ESD. METHODS: Between October 2006 and August 2011, we performed ESD on 1,000 consecutive colorectal tumors in 966 patients. We evaluated the clinical outcomes of all said cases. RESULTS: The mean resected tumor size was 24.1 ± 13.3 (3-145) mm. Our overall endoscopic en bloc resection rate was 97.5% (975/1,000), and our R0 resection rate was 91.2% (912/1,000) respectively. Our perforation rate was 5.3% (53/1,000). Of these 53 perforations, 50 cases were treated through conservative management with/without endoscopic clipping, whereas the remaining 3 patients received laparoscopic operation. Pathological examination showed adenocarcinoma in 37.2% of cases (372/1,000) and neuroendocrine tumors in 11.2% (112/1,000). We recommended additional radical surgery to 82 patients who had a risk of lymph node metastasis. Follow-up colonoscopies were performed on 722 patients. During the median follow-up period of 13 (1-62) months, there were three recurrences (0.4%). CONCLUSIONS: ESD is technically difficult, with a substantial risk of perforation. However, ESD enabled en bloc resection and pathologically complete resection of large colorectal epithelial tumors and submucosal tumors. As experience with the technique increases, ESD may gradually replace piecemeal endoscopic mucosal resection and radical colon resection in the treatment of colorectal tumors.

Laparoscopic Ventral Mesh Rectopexy (LVMR) for Internal and External Rectal Prolapse: An Analysis of 122 Consecutive Patients.

BACKGROUND: Even though several reports have been published on the results of laparoscopic ventral mesh rectopexy (LVMR) in Asia, there are few mid-term or long-term results of LVMR. The authors aimed to evaluate the results of LVMR in patients with internal rectal prolapse (IRP) external rectal prolapse (ERP). MATERIALS AND METHODS: From September 2013 to January 2019, 122 patients with IRP (n=48) or ERP (n=74) underwent LVMR. Constipation and fecal incontinence (FI) scores were evaluated using the Cleveland Clinic Florida score preoperatively and postoperatively. The questionnaire for the change of obstructed defecation or FI symptoms after surgery was also administered to grade the results as cured, improved, unchanged, or worsened for each survey. RESULTS: The mean age of the patients was 61.9 years. The mean operation time was 116.5 minutes, and the mean hospital stay was 5.1 days. The mean follow-up was 42.1 months. There were no mesh-related complications. Eight patients (10.7%) among the ERP group required additional surgery for recurrent full-thickness prolapse. Eleven patients (14.7%) who had mucosal prolapse within 2 cm underwent stapled hemorrhoidopexy after LVMR. In the postoperative 6-month period, the overall constipation score (7.12) significantly improved compared with the preoperative score (13.03) (P<0.001), whereas the FI score significantly improved after surgery (12.16 to 8.92; P<0.001). CONCLUSION: LVMR is a feasible and safe technique and favorable recurrence for ERP. Functional outcomes of obstructed defecation and FI were improved and the satisfaction of LVMR was high after the surgery. LVMR can be considered a recommended surgical option to treat ERP and IRP.

Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): A long-term prospective, multicentre, cohort study.

BACKGROUND: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery. METHODS: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). FINDINGS: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval  [CI], -1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (-8•0 points; 95% CI, -14•1 to -1•8, p = 0•0108), male sexual problems (-19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (-5•4 points on a 35-point scale; 95% CI, -8•0 to -2•7, p < 0•0001). The 5-year overall survival was worse with abdominoperineal resection in unadjusted (92•2% vs 80•9%; difference 11•3%, hazard ratio 2•38; 95% CI, 1•27 to 4•46, p = 0•0052), but did not differ after adjustment. INTERPRETATION: In this long-term prospective study, abdominoperineal resection failed to meet the superiority to sphincter preservation surgery in terms of quality of life. Although the global quality of life scores did not differ between groups, this study suggests that sphincter preservation surgery can be an acceptable alternative to abdominoperineal resection for low rectal cancer, offering a better quality of life and sexual-urinary functions, with no increased oncological risk even after 3 years. FUNDING: Seoul National University Bundang Hospital, Korea.

Colonoscopy screening for individuals aged 40-49 years with a family history of stomach cancer in Korea.

BACKGROUND: For asymptomatic individuals aged 40-49 years, screening for colorectal cancer is recommended only if individuals are at an increased risk. A family history of colon cancer (FHCRC) is considered to increase risk, however, whether family history of stomach cancer (FHSC) increases the risk of adenoma is not well known. We aimed to see whether FHSC increases the risk in asymptomatic individuals aged 40-49 years in Korea. METHODS: Among asymptomatic individual aged 40-49 years who underwent colonoscopy screening, risk of adenoma was assessed according to FHCRC or FHSC. RESULTS: Of 3,160 individuals, male comprised 1,602 individuals (50.7%). FHCRC and FHSC was noticed in 163 (5.2%) and 227 (7.0%) individuals, respectively. Prevalence of adenoma was 31.9 %, 28.8%, and 22.3% for individuals with FHCRC, individuals with FHSC, and individuals without family history of cancer, respectively. FHSC was an independent risk factor for adenoma (odds ratio, 1.38; 95% confidence interval, 1.02-1.87, P = 0.039) in asymptomatic individuals aged 40-49 years. Compared with individuals with FHCRC, individuals with FHSC showed no difference in risk for adenoma (P = 0.347). CONCLUSIONS: As with individuals with FHCRC, individuals with FHSC might need to be considered as an individual with increased risk for adenoma. Therefore, earlier screening might be needed for asymptomatic individuals aged 40-49 years with FHSC in Korea.

Nomogram Development and External Validation for Predicting the Risk of Lymph Node Metastasis in T1 Colorectal Cancer.

PURPOSE: Predicting lymph node metastasis (LNM) risk is crucial in determining further treatment strategies following endoscopic resection of T1 colorectal cancer (CRC). This study aimed to establish a new prediction model for the risk of LNM in T1 CRC patients. MATERIALS AND METHODS: The development set included 833 patients with T1 CRC who had undergone endoscopic (n=154) or surgical (n=679) resection at the National Cancer Center. The validation set included 722 T1 CRC patients who had undergone endoscopic (n=249) or surgical (n=473) resection at Daehang Hospital. A logistic regression model was used to construct the prediction model. To assess the performance of prediction model, discrimination was evaluated using the receiver operating characteristic (ROC) curves with area under the ROC curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (HL) goodness-of-fit test. RESULTS: Five independent risk factors were determined in the multivariable model, including vascular invasion, high-grade histology, submucosal invasion, budding, and background adenoma. In final prediction model, the performance of the model was good that the AUC was 0.812 (95% confidence interval [CI], 0.770 to 0.855) and the HL chi-squared test statistic was 1.266 (p=0.737). In external validation, the performance was still good that the AUC was 0.771 (95% CI, 0.708 to 0.834) and the p-value of the HL chi-squared test was 0.040. We constructed the nomogram with the final prediction model. CONCLUSION: We presented an externally validated new prediction model for LNM risk in T1 CRC patients, guiding decision making in determining whether additional surgery is required after endoscopic resection of T1 CRC.

Persistent Bleeding Following a Stapled Hemorrhoidopexy.

A stapled hemorrhoidopexy (SH) is widely used for treatment of patients with grades III and IV hemorrhoids. The SH is easy to perform, is associated with less pain and allows early return to normal activities. However, complications, whether severe or not, have been reported. Here, we present the case of a female patient with persistent bleeding after a SH. The bleeding was caused by the formation of granulation tissue at the stapler line, diagnosed with sigmoidoscopy, and successfully treated via transanal excision (TAE) under spinal anesthesia. The biopsy showed inflammatory granulation tissue. After the TAE, her symptom was completely gone.

Endoscopic submucosal dissection for nonpedunculated submucosal invasive colorectal cancer: is it feasible?

BACKGROUND/AIMS: There have been no definite indications for additional surgical resection after endoscopic submucosal dissection (ESD) of submucosal invasive colorectal cancer (SICC). The aims of this study were to evaluate the feasibility of ESD for nonpedunculated SICC and to determine the need for subsequent surgery after ESD. PATIENTS AND METHODS: A total of 150 patients with nonpedunculated SICC in resected specimens after ESD were analyzed. Among them, 75 patients underwent subsequent surgery after ESD. Clinical outcomes of ESD and histopathological risk factors for lymph node (LN) metastasis were evaluated. RESULTS: The en-bloc resection and complete resection (R0) rates of ESD were 98% (147/150) and 95.3% (143/150), respectively. None of the patients had delayed bleeding after ESD. Perforations occurred in seven patients (4.7%), which were successfully treated by endoscopic clipping. After subsequent surgery for 75 patients, LN metastases were found in 10 cases (13.3%). The incidence of LN metastasis was significantly higher in tumors featuring submucosal invasion of at least 1500 µm, lymphovascular invasion, and tumor budding. Multivariate analysis showed that lymphovascular invasion (P=0.034) and tumor budding (P=0.015) were significantly associated with LN metastasis. Among the 150 patients, no local recurrence or distant metastasis was detected, except one patient with risk factors and who refused subsequent surgery, during the overall median follow-up of 34 months (range, 5-63 months). CONCLUSION: ESD is feasible and may be considered as an alternative treatment option for carefully selected cases of nonpedunculated SICC, provided that the appropriate histopathological curative criteria are fulfilled in completely resectable ESD specimens.

Rectal neuroendocrine and L-cell tumors: diagnostic dilemma and therapeutic strategy.

Rectal neuroendocrine tumors (NETs) are currently divided into L-cell and non-L-cell types. In the World Health Organization 2010 classification, L-cell tumors are defined as borderline, whereas non-L-cell tumors are considered to represent malignancies. To establish differential diagnostic criteria and therapeutic strategy, we investigated the pathologic features of rectal NETs associated with lymph node metastasis and the clinicopathologic significance of the L-cell phenotype. We analyzed 284 patients with rectal NETs. Factors, including T stage, mitosis, histologic pattern, lymphatic invasion, tumor border, and lymph node metastasis, were retrospectively evaluated. We also evaluated tumor immunoreactivity for L-cell markers, including glucagon-like peptide 1, pancreatic peptide, and peptide YY, in 240 cases. L-cell immunoreactivity was detected in 189 of 240 NETs (79%). Of the factors evaluated, only age and the frequency of lymphatic invasion were significantly different between patients with L-cell and non-L-cell tumors. Of the 284 patients, 18 (6.3%) had lymph node metastases. Lymphatic invasion and T stage were independent risk factors for lymph node metastasis. Subgroup analysis based on tumor size showed lymph node metastasis in 0%, 4%, 24%, and 100% of patients with NETs with a size of <5, 5 to 9, 10 to 14, and ≥ 15 mm, respectively. Depth of tumor invasion, lymphatic invasion, and mitosis were correlated with tumor size (P<0.0001). In conclusion, L-cell phenotype alone does not guarantee favorable biological characteristics. The clinical management of rectal NETs should depend on tumor size. Careful pathologic examination of lymphatic invasion is necessary.

Long-term follow-up of preoperative pelvic radiation therapy and concomitant boost irradiation in locally advanced rectal cancer patients: a multi-institutional phase II study (KROG 04-01).

PURPOSE: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. METHODS AND MATERIALS: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. RESULTS: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P=.045) and N (P=.032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P=.025) and overall survival (P=.031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. CONCLUSION: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.

Magnesium citrate with a single dose of sodium phosphate for colonoscopy bowel preparation.

AIM: To evaluate the efficacy and acceptability of magnesium citrate and a single dose of oral sodium phosphate (45 mL) solution for morning colonoscopy bowel preparation. METHODS: A total of 159 patients were randomly assigned to receive two split doses of 90 mg of sodium phosphate (Group I, n = 79) or magnesium citrate (250 mL, the day before the procedure) followed by 45 mL of sodium phosphate (the day of procedure, Group II, n = 80). The quality of bowel cleansing and the acceptability of each regimen were compared, including the satisfaction, taste, willing to repeat and adverse effects of each regimen. RESULTS: The quality of bowel cleansing of Group II was as good as that of Group I (An Aronchick scale score of good or excellent: 70.9% vs 81.0%, respectively, P = 0.34; the Ottawa system score: 4.4 ± 2.6 vs 3.8 ± 3.0, respectively, P = 0.76). There was no statistically significant difference between both groups with regard to acceptability, including the satisfaction, taste and willingness to repeat the regimen. A significantly greater number of older patients (over 65 years old) in Group II graded the overall satisfaction as satisfactory (48.1% vs 78.1%, respectively; Group I vs Group II, P = 0.01). There were no significant adverse reactions. CONCLUSION: Magnesium citrate and a single dose of sodium phosphate was as effective and tolerable as the conventional sodium phosphate regimen and is a satisfactory option.

A case of Crohn's disease with improvement after azathioprine-induced pancytopenia.

The immunosuppressant azathioprine (AZA) is widely used in the treatment of inflammatory bowel disease (IBD) for both inducing and maintaining remission. However, the adverse effects of AZA can often necessitate a dose reduction or discontinuation. Bone marrow suppression is one of the most serious complications with AZA treatment. On the other hand, some reports have suggested that neutropenia during AZA therapy reduced the relapse rates of IBD patients, and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the IBD, which may explain the relevant role of neutropenia in controlling disease activity. This report describes the case of a 22-year-old male patient who had Crohn's colitis and complicated perianal fistulas that required immunosuppression; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the AZA-induced pancytopenia.