Dae Kyung Sohn

Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial

BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated. The aim of the randomised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy. METHODS Between April 4, 2006, and Aug 26, 2009, patients with cT3N0-2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals. Patients were randomised 1:1 to receive either open surgery (n=170) or laparoscopic surgery (n=170), stratified according to sex and preoperative chemotherapy regimen. Short-term outcomes assessed were involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, recovery of bowel function, perioperative morbidity, postoperative pain, and quality of life. Analyses were based on the intention-to-treat population. Patients continue to be followed up for the primary outcome (3-year disease-free survival). This study is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS Two patients (1.2%) in the laparoscopic group were converted to open surgery, but were included in the laparoscopic group for analyses. Estimated blood loss was less in the laparoscopic group than in the open group (median 217.5 mL [150.0-400.0] in the open group vs 200.0 mL [100.0-300.0] in the laparoscopic group, p=0.006), although surgery time was longer in the laparoscopic group (mean 244.9 min [SD 75.4] vs 197.0 min [62.9], p<0.0001). Involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, and perioperative morbidity did not differ between the two groups. The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group (time to pass first flatus, median 38.5 h [23.0-53.0] vs 60.0 h [43.0-73.0], p<0.0001; time to resume a normal diet, 85.0 h [66.0-95.0] vs 93.0 h [86.0-121.0], p<0.0001; time to first defecation, 96.5 h [70.0-125.0] vs 123 h [94.0-156.0], p<0.0001). The total amount of morphine used was less in the laparoscopic group than in the open group (median 107.2 mg [80.0-150.0] vs 156.9 mg [117.0-185.2], p<0.0001). 3 months after proctectomy or ileostomy takedown, the laparoscopic group showed better physical functioning score than the open group (0.501 [n=122] vs -4.970 [n=128], p=0.0073), less fatigue (-5.659 [n=122] vs 0.098 [n=129], p=0.0206), and fewer micturition (-2.583 [n=122] vs 4.725 [n=129], p=0.0002), gastrointestinal (-0.400 [n=122] vs 4.331 [n=129], p=0.0102), and defecation problems (0.535 [n=103] vs 5.327 [n=99], p=0.0184) in repeated measures analysis of covariance, adjusted for baseline values. INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery; the quality of oncological resection was equivalent.

Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial

BACKGROUND Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. METHODS The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18-80 years) with cT3N0-2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0-78·6) for the open surgery group and 79·2% (72·3-84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (-6·7%, 95% CI -15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. INTERPRETATION Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. FUNDING National Cancer Center, South Korea.

The usefulness of preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for localization in laparoscopic colorectal surgery

BackgroundLaparoscopic surgery for colorectal neoplasm requires precise tumor localization. The authors have assessed the safety and efficacy of colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for tumor localization in laparoscopic colorectal surgery.MethodsBetween July 2004 and January 2007, 63 patients underwent colonoscopic tattooing using prepackaged sterile India ink before laparoscopic surgery of colorectal tumors. Patient medical records and operation videos were retrospectively assessed.ResultsTattoos were visualized intraoperatively in 62 (98.4%) of the 63 patients, and colorectal tumors were accurately localized in 61 patients (96.8%). In one patient, the tattoo could not be detected, whereas in another patient, it was visualized but the serosal surface of the rectosigmoid colon was stained diffusely. Both of these patients underwent intraoperative colonoscopy. Localized leakages of ink were identified in six patients (9.5%) during surgery. However, five of these patients had no symptoms, and the sixth patient, who underwent polypectomy and tattooing simultaneously, felt mild chilling without fever or abdominal pain.ConclusionsPreoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink is a safe and effective method for tumor localization in laparoscopic colorectal surgery.

Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type.

Aims: To evaluate the histopathological risk factors for lymph node metastasis in cases of pedunculated or semipedunculated submucosal invasive colorectal carcinoma (SICC). Methods: A total of 48 patients with non-sessile SICC who underwent systematic lymph node dissection were included. Tumour size, histological grade, angiolymphatic invasion, tumour budding, dedifferentiation, objective submucosal invasion depth from the identified muscularis mucosa, relative invasion depth of the submucosal layer, and depth of stalk invasion were investigated histopathologically. Results: Lymph node metastasis was observed in seven cases (14.6%). Univariate analysis showed angiolymphatic invasion and tumour budding to be significantly associated with lymph node metastasis. Multivariate analysis showed that tumour budding was the only independent factor associated with lymph node metastasis in cases of non-sessile SICC. Conclusions: Results indicate that tumour budding is a useful risk factor for predicting lymph node metastasis in cases of pedunculated or semipedunculated SICC.

Indications for subsequent surgery after endoscopic resection of submucosally invasive colorectal carcinomas: a prospective cohort study.

PURPOSE: This study explored predictive factors that affected oncologic outcomes after surgical resection or follow-up without surgery in patients with submucosally invasive colorectal carcinomas after endoscopic resection. METHODS: Oncologic outcomes in terms of lymph node metastasis or tumor recurrence were assessed according to resection margin, histology, and depth of invasion. RESULTS: Eighty-seven patients with submucosally invasive colorectal carcinomas after endoscopic resection were followed prospectively. Fifty-seven (65.5 percent) patients had risk factors of deep submucosal invasion and/or unfavorable histology. Among them, 30 underwent radical resection, and 6 patients had lymph node metastases. Twenty patients with risk factors were closely followed up and 3 recurrent carcinomas were detected. Ultimately, 9 of 57 high-risk patients (15.8 percent) exhibited lymph node metastasis or tumor recurrence. Among 30 patients without risk factors, none had lymph node metastasis or recurrent carcinoma. Univariate analysis showed that tumor budding (P = 0.003) and venous invasion (P = 0.021) were factors for lymph node metastasis. In multivariate analysis, only tumor budding was an independent predictor of lymph node metastasis (P = 0.026). CONCLUSIONS: Approximately 16 percent of patients with submucosally invasive colorectal carcinoma and risk factors benefited from subsequent surgery. Tumor budding was the most significant factor for lymph node metastasis. Observation would be appropriate for patients without risk factors after endoscopic resection.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

PURPOSE To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). METHODS AND MATERIALS In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume--post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. CONCLUSIONS Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

Predictors for lymph node metastasis in T1 colorectal cancer.

BACKGROUND AND STUDY AIMS It is critical that the risk of lymph node metastasis (LNM) is evaluated for determining the suitability of endoscopic resection for T1 colorectal cancer (CRC). Reported risk factors for LNM in completely resected T1 CRC are deep submucosal invasion, grade 3, angiolymphatic invasion, and budding. The aim of the present study was to identify the histopathologic factors associated with LNM in T1 CRC. PATIENTS AND METHODS The study involved 435 patients with T1 CRC treated by endoscopic or surgical resection between January 2001 and April 2010 at the National Cancer Center, Korea. The 435 patients were classified into two groups - those undergoing surgical resection (n = 324) and those undergoing endoscopic resection (n = 111). In the surgically resected group, details regarding depth of submucosal invasion, angiolymphatic invasion, tumor grade, budding, and background adenoma (BGA) were evaluated with respect to presence or absence of LNM. In the endoscopically resected group, the results of follow-ups and additional salvage surgeries were studied. RESULTS In the surgically resected group, LNM was detected in 42 patients (13.0 %). Grade 3, angiolymphatic invasion, budding, and the absence of BGA were identified as factors associated with LNM in univariate and multivariate analyses (P < 0.05). Among the 50 patients in the endoscopically resected group with high risk, three were diagnosed as being LNM-positive during the follow-up period. There was no LNM in the endoscopically resected group with low risk. CONCLUSIONS Grade 3, angiolymphatic invasion, budding, and the absence of BGA are the risk factors that predict LNM in patients with T1 CRC. In cases where endoscopically resected T1 CRC has no risk factor, cautious follow-up could be recommended. However, if the tumor has any risk factor, additional surgical resection should be considered.

Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance

BACKGROUND AND STUDY AIMS Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers. PATIENTS AND METHODS Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes. RESULTS Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types ( P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors. CONCLUSIONS Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk.

Associations of Cigarette Smoking and Alcohol Consumption With Advanced or Multiple Colorectal Adenoma Risks: A Colonoscopy-based Case-Control Study in Korea

The associations between alcohol consumption and cigarette smoking habits and the risk for colorectal adenomatous polyps according to the detailed clinical information about polyps were assessed in a large colonoscopy-based study. The study enrolled participants who visited the National Cancer Center of the Republic of Korea for cancer screening between April 2007 and April 2009. In 1,242 newly diagnosed colorectal adenoma patients and 3,019 polyp-free controls, past smokers (odds ratio (OR) = 1.31, 95% confidence interval (CI): 1.04, 1.65) and current smokers (OR = 1.70, 95% CI: 1.37, 2.11) had increased risks for adenomas compared with nonsmokers. Cigarette smoking conferred an even higher risk for advanced adenomas and 3 or more adenomas than for low-risk adenomas or a single adenoma. Dose-response relations were observed among the daily number of cigarettes smoked, the duration of smoking, the pack-years of smoking, and the risk for adenomas. A longer duration of alcohol consumption was associated with a higher risk for advanced adenomas (for >28 years of consumption: OR = 2.0, 95% CI: 1.10, 3.64) and 3 or more adenomas (OR = 2.19, 95% CI: 1.27, 3.76). In conclusion, cigarette smoking and alcohol consumption play roles in colorectal carcinogenesis, and the association differs by the clinical features of the adenomas.

Single Immunochemical Fecal Occult Blood Test for Detection of Colorectal Neoplasia

PURPOSE This study was designed to investigate the validity of a single immunochemical fecal occult blood test (FOBT) for detection of colorectal neoplasia. MATERIALS AND METHODS A total of 3,794 average-risk screenees and 304 colorectal cancer patients admitted to the National Cancer Center, Korea, between May 2001 and November 2002, were studied prospectively. All screenees and admitted patients underwent FOBT and total colonoscopic examinations. Stools were self-collected, and examined using an immunochemical fecal occult blood test (OC-hemodia, Eiken Chemical Co. Tokyo, Japan) and an OC-sensor analyzer(R) (Eiken Chemical Co. Tokyo, Japan). RESULTS Of the 3,794 asymptomatic screenees, the colonoscopy identified colorectal adenomas and cancers in 613 (16.2%) and 12 (0.3%) subjects, respectively. The sensitivities of a single immunochemical FOBT for detecting colorectal cancers and adenomas in screenees were 25.0 and 2.4%, respectively. The false positive rate of FOBT for colorectal cancer in screenees was 1.19%. For the total 316 colorectal cancer cases (including 12 cases from screenees), the FOBT sensitivities according to the T-stage were 38.5, 75.0%, 78.9 and 79.2% for T1, 2, 3 and 4 cancers, respectively. The sensitivities according to the Dukes stages A, B and C were 63.4, 79.3 and 78.6%, respectively. CONCLUSION The sensitivities of a single immunochemical FOBT for detecting colorectal cancers and adenomas in screenees were 25.0 and 2.4%, respectively. The sensitivities of FOBT were about 80% for Dukes B or C colorectal cancers and 63.4% for Dukes A.