Three-year colonoscopy surveillance after polypectomy in Korea: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter prospective study

BACKGROUND/AIMS: Colonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy. METHODS: A total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics. RESULTS: Among 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence. CONCLUSIONS: A colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.

Sodium Picosulfate with Magnesium Citrate (SPMC) Plus Laxative Is a Good Alternative to Conventional Large Volume Polyethylene Glycol in Bowel Preparation: A Multicenter Randomized Single-Blinded Trial

BACKGROUND/AIMS: We investigated whether sodium picosulfate with magnesium citrate (SPMC) plus bisacodyl compares favorably with conventional polyethylene glycol (PEG) with respect to bowel cleansing adequacy, compliance, and safety. METHODS: We performed a multicenter, prospective, single-blinded study in outpatients undergoing daytime colonoscopies. Patients were randomized into a split preparation SPMC/bisacodyl group and a conventional split PEG group. We compared preparation adequacy using the Boston bowel preparation scale (BBPS), ease of use using a modified Likert scale (LS), compliance/satisfaction level using a visual analogue scale (VAS), and safety by monitoring adverse events during the colonoscopy between the two groups. RESULTS: A total of 365 patients were evaluated by intention to treat (ITT) analysis, and 319 were evaluated by per protocol (PP) population analysis (153 for SPMC/bisacodyl, 166 for PEG). The mean total BBPS score was not different between the two groups in both the ITT and PP analyses (p>0.05). The mean VAS score for satisfaction and LS score for the ease of use were higher in the SPMC/bisacodyl group (p<0.001). The adverse event rate was lower in the SPMC/bisacodyl group than in the PEG group (p<0.05). CONCLUSIONS: The SPMC/bisacodyl treatment was comparable to conventional PEG with respect to bowel preparation adequacy and superior with respect to compliance, satisfaction, and safety.

Long-Term Clinical Outcomes of Korean Patient With Crohn's Disease Following Early Use of Infliximab

BACKGROUND/AIMS: Several recent studies have reported that the early use of infliximab (IFX) improves the prognosis of Crohn's disease (CD). However, no data are available from Asian populations, as the forementioned studies have all been conducted in Western countries. The aim of the current study was to evaluate the impact of early use of IFX on the prognosis of Korean patients with CD. METHODS: Patients with a diagnosis of CD established between July 1987 and January 2012 were investigated in 12 university hospitals in Korea. Because insurance coverage for IFX treatment began in August 2005, patients were assigned to either of 2 groups based on diagnosis date. The first group included patients diagnosed from July 1987 to December 2005, and the second from January 2006 to January 2012. We compared the cumulative probabilities of operation and reoperation between the two groups using the Kaplan-Meier method and a log-rank test. RESULTS: Of the 721 patients investigated, 443 (61.4%) comprized the second group. Although the cumulative probabilities of immunosuppressant (P<0.001) and IFX use (P<0.001) after diagnosis were significantly higher in the second group, there were no significant differences in cumulative probabilities of operation (P=0.905) or reoperation (P=0.418) between two groups. CONCLUSIONS: The early use of IFX did not reduce CD-related surgery requirements in Korean patients with CD. These study results suggest that the early use of IFX may have little impact on the clinical outcome of CD in Korean patients in the setting of a conventional step-up algorithm.

The Effect of Infliximab on Patients with Ulcerative Colitis in Korea

BACKGROUND/AIMS: Infliximab was introduced recently as a rescue therapy for ulcerative colitis (UC) patients refractory to conventional treatments such as therapy with 5-amiono salicylic acids (5-ASA), immune modulators, and corticosteroids. However, there is insufficient data about its efficacy and safety in Korea. METHODS: From 7 tertiary referral hospitals, 33 patients who were treated with infliximab for moderate to severe (Mayo score 6-12) UC refractory to conventional treatment were recruited to this study. Clinical remission was defined as a total Mayo score of 2 or lower and every subscore less than 2. Partial response was defined as a decrease of Mayo score at least 3 points from baseline. RESULTS: Twenty-three patients (69.7%) showed clinical remission and 29 patients (87.8%) showed partial response in the observation period. When the remission and non-remission groups were compared in univariate analysis, only a higher total Mayo score at base line (11.0+/-0.9 vs. 9.9+/-1.5; P=0.04) was related to remission. The remission maintenance rate decreased with time in the Kaplan-Meier analysis. Two patients experienced re-remission after the first remission followed by aggravation during infliximab treatment. Three patients stopped infliximab treatment owing to adverse events including rhabdomyolysis, pneumonia, and fever of unknown origin. CONCLUSIONS: If there is no choice except surgery for UC patients refractory to conventional treatment, infliximab is an effective and relatively safe treatment option for these patients in Korea.

Usefulness of Polyp and Adenoma Detection Rate in the Proximal and Distal Colon / 대한소화기학회지

BACKGROUND/AIMS: The polyp detection rate (PDR) has been suggested as a surrogate for adenoma detection rate (ADR). The purpose of this study was to determine the level of agreement between PDR and ADR in the proximal and distal colon. METHODS: A total of 1,937 consecutive, asymptomatic individuals aged 40 years and older who underwent colonoscopies at six academic teaching hospitals in Korea were included in this study. PDR and ADR were calculated for each colonic segment. PDR was compared with ADR in the proximal and distal colon. RESULTS: During 1,937 colonoscopies, 1,862 polyps were removed; 1,421 (76%) were adenomas. The PDR and ADR in the proximal colon was 25.8% and 22.8%, respectively (kappa value=0.917, p=0.26), and that in the distal colon was 28.9% and 22.2%, respectively (p<0.001). There was a strong correlation between PDR and ADR in the proximal colon, but diverged in sigmoid colon and rectum. CONCLUSIONS: PDR and ADR correlate well in the proximal colon, but not in the distal colon, especially sigmoid and rectum. PDR should be measured for each colonic segment when using PDR as a surrogate for ADR. PDR is a valid proxy for ADR in the proximal colon.

A Clear Liquid Diet Is Not Mandatory for Polyethylene Glycol-Based Bowel Preparation for Afternoon Colonoscopy in Healthy Outpatients

BACKGROUND/AIMS: A dietary regimen consisting of a clear liquid diet (CLD) for at least 24 hours is recommended for colonoscopy preparation. However, this requirement results in problems in patient compliance with bowel preparation. The aim of this study was to evaluate the efficacy of a CLD compared with a regular diet (RD) for colonoscopy preparation using a polyethylene glycol (PEG) solution. METHODS: This was a multicenter, randomized, investigator-blind prospective study. A total of 801 healthy outpatients undergoing afternoon colonoscopy were randomized to either a CLD or RD in addition to a 4 L PEG regimen. RESULTS: The quality of bowel cleansing was not different between the CLD and RD groups in terms of the proportion with excellent or good preparation. In addition, no significant differences were observed between the two groups for polyp and adenoma detection rates and overall adverse events. Good compliance with bowel preparation was higher in the RD group than in the CLD group. CONCLUSIONS: A CLD for a full day prior to colonoscopy should not be mandatory for PEG-based bowel preparation. Dietary education concerning the avoidance of high-fiber foods for 3 days before colonoscopy is sufficient, at least for healthy outpatients.

A Survey of the Radiation Exposure Protection of Health Care Providers during Endoscopic Retrograde Cholangiopancreatography in Korea

BACKGROUND/AIMS: During endoscopic retrograde cholangiopancreatography (ERCP), all efforts should be made to be aware of radiation hazards and to reduce radiation exposure. The aim of this study was to investigate the status of radiation protective equipment and the awareness of radiation exposure in health care providers performing ERCP in Korean hospitals. METHODS: A survey with a total of 42 questions was sent to each respondent via mail or e-mail between October 2010 and March 2011. The survey targeted nurses and radiation technicians who participated in ERCP in secondary or tertiary referral centers. RESULTS: A total of 78 providers from 38 hospitals responded to the surveys (response rate, 52%). The preparation and actual utilization rates of protective equipment were 55.3% and 61.9% for lead shields, 100% and 98.7% for lead aprons, 47.4% and 37.8% for lead glasses, 97.4% and 94.7% for thyroid shields, and 57.7% and 68.9% for radiation dosimeters, respectively. The common reason for not wearing protective equipment was that the equipment was bothersome, according to 45.7% of the respondents. CONCLUSIONS: More protective equipment, such as lead shields and lead glasses, should be provided to health care providers involved in ERCP. In particular, the actual utilization rate for lead glasses was very low.

Clinical Practice of Surveillance Colonoscopy according to the Classification of Colorectal Intraepithelial Neoplasia in Korea: High-grade Dysplasia/Carcinoma In Situ Versus Intramucosal Carcinoma

BACKGROUND/AIMS: Recent guidelines strongly recommend that the interval of surveillance colonoscopy be determined according to the risk stratification obtained at index colonoscopy. However, because of the differences in perception of the classification of colorectal intraepithelial neoplasia between Asian and Western countries, there is some confusion about surveillance colonoscopy. The aim of the present study was to evaluate the clinicopathological characteristics and the interval of surveillance colonoscopy between patients with high-grade dysplasia/carcinoma in situ and those with intramucosal carcinoma. METHODS: From January 2003 to June 2010, 727 patients were included from 8 tertiary centers. Four hundred fifteen patients (57.1%) had high-grade dysplasia/carcinoma in situ (group A), and 312 (43.9%) had intramucosal carcinoma (group B). Clinicopathological data were reviewed retrospectively. RESULTS: Group A had a significantly more frequent family history of colorectal cancer (3.1% vs. 0.6%, P<0.001), smaller polyp size (12 mm vs. 15 mm, P=0.001), and more proximal location (31.1% vs. 21.8%, P=0.005) than did group B. Among 727 patients, surveillance colonoscopy was performed within 6 months in 55.8% of patients and within 12 months in 77.8%. Group B had a significantly shorter interval of surveillance colonoscopy than did group A (P<0.001). There was no difference in detection of advanced neoplasia at surveillance colonoscopy between the 2 groups (6.6% vs. 5.4%, P=0.638). CONCLUSIONS: The recommended interval of surveillance colonoscopy is not followed in Korea. More education about post-polypectomy surveillance guidelines is required.

Variable Clinical Classifications and Diagnostic Coding Systems of Colorectal Neuroendocrine Tumor

The incidence of colorectal carcinoid tumor is recently increasing as screening colonoscopy increased. Traditional carcinoid tumor had been known as low grade, malignant neuroendocrine cell orign tumor. In 2000, World Health Organization (WHO) suggested that carcinoid was called well-differentiated neuroendocrine tumor (NET). It recently updated in 2010 by WHO; according to the differentiation and malignant potential, NET classified with NET Grade 1, Grade 2, and neuroendocrine carcinoma. They suggested that NET had malignant potential in accordance with histopathologic characteristics. Therefore, WHO recommended the behavior code of NET as malignant. However, European Neuroendocrine Tumor Society (ENETS) proposed the behavior of NET to four grades based on the histopathologic features; benign, benign or low grade malignant, low grade malignant, and high grade malignant. Also, American Joint Committee on Cancer (AJCC) suggested that topography codes of NET were defined as malignant. Korean Standard Classification of Diseases (KCD) described the different codings of carcinoid (NET). The discrepancies of behavior code or coding system exist among WHO, ENETS, AJCC and KCD. Also, there were differences in the perception for topographic coding system between clinicians and pathologists. NETs of colorectum were reported with the variable clinical characteristics (especially, metastasis) and long term prognosis from many studies. Especially, risk of metastasis and long term prognosis of small sized NET (<1 cm) had some discrepancies and should be investigated prospectively. Therefore, the consensus about topographic codes of NET should be needed with multidisplinary approach among gastroenterologists, pathologists and surgeons.

Seasonal Variation in Months of Birth and Symptom Flares in Korean Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Seasonal variation may influence the development and exacerbation of inflammatory bowel disease (IBD). However, most epidemiologic studies on this topic have been conducted in Western countries. The purpose of this study was to determine whether birth dates and symptom flares follow a seasonal pattern in Korean patients with IBD. METHODS: Patients with a diagnosis of IBD established between January 2003 and December 2010 were investigated at six university hospitals in Korea. The expected births and flares, with a uniform distribution during the year and considering differences in the number of days in the months of 1 year, were calculated. RESULTS: A total of 411 patients with ulcerative colitis (UC) and 316 patients with Crohn disease (CD) were included in the study. Birth during the winter period, and especially in January and February, was associated with an increased risk of IBD, especially in UC patients. The symptom flares of CD patients occurred most frequently in the spring, with a nadir in the autumn. However, no disease flare seasonality was noted for UC patients. CONCLUSIONS: Our data suggest that seasonally varying environmental factors during pregnancy and the postpartum period are associated with a susceptibility to IBD later in life and that exacerbations of CD are influenced by seasonal factors.

Endoscopic Removal of a Proximally Migrated Metal Stent during Balloon Sweeping after Stent Trimming

Placement of a self-expanding metal stent (SEMS) is an effective method for palliation of a malignant biliary obstruction. However, metal stents can cause various complications, including stent migration. Distally migrated metal stents, particularly covered SEMS, can be removed successfully in most cases. Stent trimming using argon plasma coagulation may be helpful in difficult cases despite conventional methods. However, no serious complications related to the trimming or remnant stent removal method have been reported due to the limited number of cases. In particular, proximal migration of a remnant fragmented metal stent after stent trimming followed by balloon sweeping has not been reported. We report an unusual case of proximal migration of a remnant metal stent during balloon sweeping following stent trimming by argon plasma coagulation. The remnant metal stent was successfully removed with rotation technique using a basket and revised endoscopically.

A Korean National Survey for Colorectal Cancer Screening and Polyp Diagnosis Methods Using Web-based Survey / 대한소화기학회지

BACKGROUND/AIMS: There is a paucity of national guideline for colorectal cancer screening and polyp diagnosis in Korea. Thus, we investigated the present state of colorectal cancer screening and polyp diagnosis methods using web-based survey to use as reference data for developing a guideline. METHODS: A multiple choice questionnaires of screening recommendations was sent via e-mail to members of the Korean Association for the Study of Intestinal Diseases and primary care physicians who participated in the national colonoscopy surveillance program. Among 425 colonoscopists, a total 263 colonoscopists replied (response rate, 61.9%). RESULTS: The most commonly recommended starting age for colorectal cancer screening and polyp diagnosis was 50 years old in the average risk group, and 40 years old in groups who had a family history of colon cancer (64.3% and 65.0% respectively). Surgeons had a tendency to recommend screening in younger people than internist do. Ninety-eight percent of physicians recommended screening colonoscopy to asymptomatic, average-risk patients as a first choice. Only 2% of physicians chose sigmoidoscopy as a screening tool. When the initial colonoscopy showed a negative finding, over 60% of internists repeated the exam 5 years later, whereas 62% of surgeons did so within 3 years. CONCLUSIONS: The starting age of colorectal cancer screening and the interval of the colorectal polyp examination are not uniform in various medical environments, and there is a discrepancy between the practical recommendations and western guidelines. Thus, a new evidence-based national practice guideline for colorectal cancer screening and polyp diagnosis should be developed.

Successful Primary Infliximab Treatment of Orofacial Crohn's Disease without Gastrointestinal Manifestation / 대한소화기학회지

Crohn's disease is a chronic inflammatory bowel disease that can involve the whole gastrointestinal tract. The orofacial manifestation of Crohn's disease, which is rare, can develop irrespective of intestinal involvement. These orofacial lesions are often misdiagnosed as simple oral ulcers. Corticosteroids are the mainstay of therapy for orofacial Crohn's disease. However, infliximab, the chimeric monoclonal antibody to tumor necrosis factor-alpha, is now considered as a primary treatment because of the disease's relatively high rate of steroid resistance. We present a case of deep oral ulcer and periorbital swelling in a 65-year-old woman. She was diagnosed with intestinal Crohn's disease 7 years ago, which was in remission after treatment with an immunosuppressive agent (azathioprine). The patient was given the diagnosed with orofacial Crohn's disease and successfully treated with infliximab.

A Rare Case of Ogilvie Syndrome Associated with Herpes Zoster

Acute colonic pseudo-obstruction (Ogilvie syndrome) associated with herpes zoster is extremely rare, and few cases have been reported. An 81-year-old woman diagnosed with herpes zoster was referred for accompanying colonic ileus. The diameter of the cecum was 7 cm and a computed tomographic scan showed no definite obstructive cause. Because the patient showed minimal improvement with conservative treatment, endoscopic colonic decompression was performed successfully. Previous studies revealed that the treatment of Ogilvie syndrome associated with herpes zoster does not differ from that of other conditions, and the role of the varicella-zoster virus in this syndrome is unclear. Here, we present the first case of Ogilvie syndrome associated with herpes zoster in Korea, which was improved by endoscopic colonic decompression.

Submucosal Endoscopy, a New Era of Pure Natural Orifice Translumenal Endoscopic Surgery (NOTES)

Natural orifice translumenal endoscopic surgery (NOTES) involves the intentional perforation of the viscera with an endoscope to access the abdominal cavity and perform an intraabdominal operation. In a brief time period, NOTES has been shown to be feasible in laboratory animal and human studies. Easy access to the peritoneal cavity and complete gastric closure should be secured before NOTES can be recommended as an acceptable alternative in clinical practice. The concept of submucosal endoscopy has been introduced as a solution to overcome these two primary barriers to human NOTES application. Its offset entry/exit access method effectively prevents contamination and allows the rapid closure of the entry site with a simple mucosal apposition. In addition, it could be used as an endoscopic working space for various submucosal conditions. Herein, the detailed procedures, laboratory results and human application of the submucosal endoscopy will be reviewed.

Korean Guideline for Colonoscopic Polypectomy

There is indirect evidence to suggest that 80% of colorectal cancers (CRC) develop from adenomatous polyps and that, on average, it takes 10 years for a small polyp to transform into invasive CRC. In multiple cohort studies, colonoscopic polypectomy has been shown to significantly reduce the expected incidence of CRC by 76% to 90%. Colonoscopic polypectomy is performed frequently in primary outpatient clinics and secondary and tertiary medical centers in Korea. However, there are no evidence-based, procedural guidelines for the appropriate performance of this procedure, including the technical aspects. For the guideline presented here, PubMed, Medline, and Cochrane Library literature searches were performed. When little or no data from well-designed prospective trials were available, an emphasis was placed on the results from large series and reports from recognized experts. Thus, these guidelines for colonoscopic polypectomy are based on a critical review of the available data as well as expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data become available. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions for any particular case involve a complex analysis of the patient's condition and the available courses of action.

Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations.

Korean Guidelines for Postpolypectomy Colonoscopy Surveillance

Postpolypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. In this report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy and we elucidated the high risk findings of the index colonoscopy as follows: 3 or more adenomas, any adenoma larger than 10 mm, any tubulovillous or villous adenoma, any adenoma with high-grade dysplasia, and any serrated polyps larger than 10 mm. Surveillance colonoscopy should be performed five years after the index colonoscopy for those without any high-risk findings and three years after the index colonoscopy for those with one or more high risk findings. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polypectomy, the patient's general condition, and family and medical history.

Frequency of Bone Marrow Toxicity by Using Pattern of Azathioprine in Inflammatory Bowel Disease Patients

BACKGROUND/AIMS: The most important adverse effect of azathioprine (AZA) is bone marrow toxicity (BMT). Many physicians have preferred a gradual dose increment (GDI) policy for the prevention of BMT. The aim of this study was to evaluate the efficacy of GDI for the prevention of AZA-induced BMT in inflammatory bowel disease (IBD) patients. METHODS: The medical records of IBD patients who received AZA in 6 university hospitals were reviewed. The patients were divided into two groups: the GDI group (initial dose or =2 mg/kg). RESULTS: A total of 308 patients were enrolled (male to female ratio, 1:2.3; mean age, 34.91+/-14.19 years; ulcerative colitis, 43.5%; Crohn's disease, 55.2%; and intermediate colitis, 1.3%). The overall incidence of BMT was 16.2% (50/308). BMT developed most frequently between fourth to eighth week (26%, 13/50). The rate of BMT of the non-GDI group was significantly higher than that of the GDI group (27.5%, 11/40 vs. 14.6%, 39/268, P=0.038). A multivariate analysis showed that the only factor related to BMT was a non-GDI policy (P=0.036; odds ratio, 2.41; 95% confidence interval, 1.06-5.49). CONCLUSIONS: A GDI policy could be useful for reducing AZA-induced BMT in Korean IBD patients.

Comparison of Bowel Preparation Quality between Clear-liquid Diet and No Diet Restriction

BACKGROUND/AIMS: Adequate bowel preparation is essential for full visualization of colonic mucosa because detection of small polyps and neoplasms depends on the quality of bowel cleansing. The aims of this study were to compare the efficacy, tolerability of preparation and side effect between two groups: clear-liquid diet with polyethylene glycol (PEG) solution versus no diet restriction with PEG solution. METHODS: This was a randomized single-blind prospective study. A total of 330 patients were randomly assigned to receive either 2 L PEG solution with a clear-liquid diet on the day before colonoscopy and another 2 L PEG solution on the day of the procedure (group 1) or 2 L PEG solution with a general diet on the day before colonoscopy and another 2 L PEG solution on the day of the procedure (group 2). RESULTS: 162 patients were assigned to group 1 and 168 patients to group 2. The satisfactory quality of bowel preparation was not significantly different between the two groups (80.2%, 78.6%, P=0.707). Patient's compliance of the clear-liquid diet in group 1 was 50%. The satisfactory quality of bowel preparation was weakly better when the clear-liquid diet was given 2 or 3 times a day (group 1A) than 0 or once a day (group 1B) (74.1%, 86.4%, P=0.048). The tolerability of the PEG solution and side effects of preparation were not significantly different in the two groups (P=0.573, 0.686). CONCLUSIONS: Bowel preparation with no diet restriction and split-dose PEG solution was similar to preparation with a clear-liquid diet in efficacy, tolerability and side effect. Therefore, the use of the clear-liquid diet protocol should improve patient's compliance.