Screening and surveillance for hereditary colorectal cancer.

Hereditary colorectal cancer is a type of cancer that is caused by a genetic mutation. Individuals with a family history of colorectal cancer, or who have a known hereditary syndrome, are at an increased risk of developing the disease. Screening and surveillance are important tools for managing the risk of hereditary colorectal cancer. Screening involves a combination of tests that can detect precancerous or cancerous changes in the colon and rectum. Surveillance involves regular follow-up examinations to monitor disease progression and to identify new developments. The frequency and type of screening and surveillance tests may vary depending on an individual's risk factors, genetic profile, and medical history. However, early detection and treatment of hereditary colorectal cancer can significantly improve patient outcomes and reduce mortality rates. By implementing comprehensive screening and surveillance strategies, healthcare providers can help individuals at risk of hereditary colorectal cancer to receive timely interventions and make informed decisions about their health. Specific examples of screening and surveillance tests for hereditary colorectal cancer include colonoscopy, genetic testing, and imaging tests. In this review article, we will discuss detailed screening and surveillance of hereditary colorectal cancer.

Risk of uterine cervical cancer in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There are limited data on the association between uterine cervical cancer (UCC) and inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This systematic review and meta-analysis assessed the risk of UCC in patients with IBD. We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, gray literature and conference proceedings for studies published before 21 January 2022. Two reviewers independently screened studies, extracted data and assessed quality using the Newcastle-Ottawa Scale. Subgroup analyses were based on IBD type, biologic era, immunosuppression status, study location and design, and publication status. Fifteen studies were included. RESULTS: The pooled relative risk (RR) of UCC in IBD was 1.34 (95% confidence interval [CI], 1.07-1.69; I2 = 53.4%). In subgroup analyses, the pooled RRs of UCC in CD and UC were 1.18 (95% CI, 0.97-1.42) and 1.50 (95% CI, 1.01-12.21), respectively. The pooled RRs of UCC in pre-biologic and biologic eras were 1.36 (95% CI, 0.83-2.23) and 1.99 (95% CI, 1.03-3.86), respectively. The pooled RR of UCC in immunomodulator users was 2.18 (95% CI, 0.81-5.87). The pooled RRs of UCC in Asia, Europe and North America were 5.65 (95% CI, 2.65-12.07), 1.13 (95% CI, 0.96-1.34) and 1.38 (95% CI, 1.10-1.73), respectively. CONCLUSIONS: The risk of UCC was significantly increased in IBD, particularly in UC but not in CD, suggesting that women with IBD should undergo regular UCC screening and consider vaccination.

Elevated risk of cervical cancer in elderly women with incident ulcerative colitis in South Korea.

The association between ulcerative colitis (UC) and uterine cervical cancer is still unclear. To investigate cervical cancer risk in South Korean women with UC, we analyzed the Korean National Health Insurance claims data. UC was defined using both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases of UC diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios were calculated using multivariate Cox proportional hazard regression, and the event was defined as occurrence of cervical cancer. A total of 12,632 women with UC and 36,797 women without UC were enrolled. The incidence of cervical cancer was 38.8 per 100,000 women per year in UC patients and 25.7 per 100,000 women per year in controls, respectively. The adjusted HR for cervical cancer was 1.56 (95% CI 0.97-2.50) in the UC group with reference to the control group. When stratified by age, the adjusted HR for cervical cancer was 3.65 (95% CI 1.54-8.66) in elderly UC patients (≥ 60 years) compared to elderly control group (≥ 60 years). Within UC patients, increased age (≥ 40 years) and low socioeconomic status were associated with an increased risk of cervical cancer. The incidence of cervical cancer was found to be higher among elderly patients (≥ 60 years) with newly diagnosed UC in South Korea, compared to age-matched controls. Therefore, regular cervical cancer screening is recommended for elderly patients who have recently been diagnosed with UC.

Risk of Gastric Cancer among Patients with Newly Diagnosed Ulcerative Colitis: A Nationwide Population-Based Study.

BACKGROUND: Few studies have investigated the risk of gastric cancer (GC) in ulcerative colitis (UC), and the results have been inconsistent. This study aimed to assess the risk of gastric cancer in newly diagnosed UC patients. METHODS: Based on claims data from Korean National Health Insurance from January 2006 to December 2015, we identified 30,546 patients with UC and randomly selected 88,829 non-UC individuals as controls, who were matched by age and sex. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios (HRs) for gastric cancer events, with covariates taken into account. RESULTS: During the study period, a total of 77 (0.25%) patients with UC and 383 (0.43%) non-UC individuals were diagnosed with GC. After multivariable adjustment, the HR for GC was 0.60 (95% CI: 0.47-0.77) in patients with UC, using non-UC individuals as the reference group. When stratified by age, the adjusted HRs for GC in UC patients were 0.19 (95% CI: 0.04-0.98) for those aged 20-39 years at the time of UC diagnosis, 0.65 (95% CI: 0.45-0.94) for 40-59, and 0.60 (95% CI: 0.49-0.80) for ≥60 as compared to non-UC individuals in the corresponding age groups. When stratified by sex, the adjusted HR for GC was 0.54 (95% CI: 0.41-0.73) in male UC patients of all ages. Within UC patients, a multivariable analysis revealed that the HR for GC was 12.34 (95% CI: 2.23-68.16) for those aged ≥ 60 years at the time of diagnosis of UC. CONCLUSIONS: Patients with UC had a decreased GC risk compared with non-UC individuals in South Korea. Within the UC population, advancing age (≥60 years) was identified as a significant risk factor for GC.

Incident Crohn's Disease as a Risk Factor for Colorectal Cancer in the First 10 Years after Diagnosis: A Nationwide Population-Based Study.

We investigated the risk of colorectal cancer (CRC) in patients with Crohn's disease (CD) using the claims data of the Korean National Health Insurance during 2006-2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression tests. CRC developed in 25 patients (0.18%) and 42 patients (0.1%) of the CD and non-CD groups, respectively. The HR of CRC in the CD group was 2.07 (95% confidence interval (CI), 1.25-3.41). The HRs of CRC among men and women were 2.02 (95% CI 1.06-3.87) and 2.10 (95% CI, 0.96-4.62), respectively. The HRs of CRC in the age groups 0-19, 20-39, 40-59, and ≥60 years were 0.07, 4.86, 2.32, and 0.66, respectively. The HR of patients with late-onset CD (≥40 years) was significantly higher than that of those with early-onset CD (<40 years). CD patients were highly likely to develop CRC. Early-onset CD patients were significantly associated with an increased risk of CRC than matched individuals without CD. However, among CD patients, late-onset CD was significantly associated with an increased risk of CRC.

Medications and the Risk of Colorectal Cancer in Patients with Inflammatory Bowel Diseases: Use of the Landmark Method.

PURPOSE: This study aimed to determine whether the use of drugs in the treatment of inflammatory bowel disease is related to the risk of colorectal cancer using a Cox proportional hazards model with the landmark method to minimize immortal time bias. MATERIALS AND METHODS: This study was conducted as national cohort-based study using data from Korea's Health Insurance Corporation. Newly diagnosed patients with inflammatory bowel disease from 2006 to 2010 were monitored for colorectal cancer until 2015. Hazard ratios and 95% confidence intervals were calculated and compared with the incidence of colorectal cancer with or without medications by applying various landmark points. RESULTS: In patients with Crohn's disease, the prevention of colorectal cancer in the group exposed to immunomodulators was significant in the basic Cox model; however, the effect was not statistically significant in the model using the landmark method. The preventive effect of 5-aminosalicylic acid in patients with ulcerative colitis was significant in the basic and 6-month landmark point application models, but not in the remaining landmark application models. CONCLUSION: In patients with inflammatory bowel disease, the preventive effect of drug exposure on colorectal cancer varies depending on the application of the landmark method. Hence, the possibility of immortal time bias should be considered.

Trends in the Incidence and Survival Rates of Colorectal Signet-Ring Cell Carcinoma in the South Korean Population: Analysis of the Korea Central Cancer Registry Database.

OBJECTIVE: Signet-ring cell carcinoma (SRCC) is a rare histopathological subtype of colorectal cancer (CRC) constituting approximately 1% of CRC cases. This study analyzed the incidence and survival rates of colorectal SRCC. METHODS: We analyzed the incidence and survival rates of colorectal SRCCs based on patients' data of the Korea Central Cancer Registry. RESULTS: The age-standardized incidence rates of colon and rectum SRCC in 2017 were 0.17 and 0.07 individuals per 100,000, respectively. Between 1993 and 2017, the 1-, 2-, 3-, 4-, and 5-year relative survival rates of patients with colon SRCC were 65.6%, 49.0%, 38.9%, 34.9%, and 33.0%, respectively, while those of patients with rectum SRCC were 69.6%, 47.8%, 38.5%, 32.8%, and 29.4%, respectively. According to the Surveillance, Epidemiology, and End Results summary stages, the 5-year relative survival rates of colon SRCC between 1993 and 2017 were 70.4% for the localized stage, 41.0% for the regional stage, and 7.0% for the distant stage, while those for rectum SRCC were 60.7%, 34.4, and 3.3%, respectively. CONCLUSIONS: Although the incidence of colorectal SRCC is extremely low in South Korea, it has been increasing in recent decades. As the prognosis of colorectal SRCC is extremely poor; clinicians should be aware of the differential diagnosis of SRCC in colorectal cancer cases.

Prevalence of Regional Lymph Node Metastasis of Mucosal Gastric Signet Ring Cell Carcinoma: Analysis of the Collaborative Stage Data Survey of the Korean Central Cancer Registry.

INTRODUCTION: Patients with very early-stage gastric signet ring cell carcinoma (SRC) are eligible for minimally invasive treatment, like endoscopic submucosal dissection. However, population-based data on regional lymph node metastasis (LNM) and distant metastasis of gastric SRC are lacking. This study aimed to identify the prevalence of LNM and distant metastasis in mucosal cancer (T1a) of gastric SRC. METHODS: The Collaborative Stage Data Survey was performed by the Korean Center of Cancer Registry between 2010 and 2015 to establish collaborative stage data of the stomach, colon, rectum, rectosigmoid junction, and breast. From the survey data, information on patients with gastric SRC was extracted for analysis. Variables including age, sex, diagnosis date, primary site, tumor size, histology, American Joint Committee on Cancer staging system scores, and Surveillance, Epidemiology, and End Results summary stage were analyzed. RESULTS: A total of 1,335 (65.7%) patients had mucosal gastric SRC, and 1,189 (89.1%) patients had surgery and 134 (10%) had endoscopic treatment. Of them, 1,283 (96.1%) patients did not have regional LNM, and 52 (3.9%) patients had regional LNM and 6 (0.4%) had distant metastasis. The hazard ratios of LNM and distant metastasis were 14.98 (95% CI: 4.18-53.2) and 10.09 (95% CI: 2.30-44.17). CONCLUSIONS: Reginal LNM and distant metastasis occur very less in mucosal gastric SRC, but they are associated with an increased risk of cancer-related death. Even in early stage, surgery should be considered as a standard treatment of mucosal gastric SRC.

Age- and sex-specific risk of colorectal cancer in incident ulcerative colitis during the first 10 years after diagnosis: a nationwide population-based study.

OBJECTIVE: We assessed the risk of colorectal cancer (CRC) in patients with ulcerative colitis (UC) using the nationwide population-based claims data. MATERIALS AND METHODS: We analyzed the claims data of the Korean National Health Insurance (2006-2015). UC and CRC were defined using ICD-10 codes and UC-specific prescriptions in this study. Age- and sex-matched individuals without UC were randomly selected from the general population. Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression. RESULTS: In total, 30,546 and 88,829 individuals with and without UC, respectively, were enrolled. CRC developed in 85 (0.27%) among UC, and 340 (0.38%) among individuals without UC, respectively. The HR (95% confidence interval [CI]) of CRC in all UC patients was 0.74 (0.58-0.94). Further, UC patients were stratified according to sex (male vs. female: 0.60 [0.44-0.82] vs. 1.10 [0.75-1.61]) and age (HR = 14.37, 2.74, 0.58, and 0.70 for 0-19, 20-39, 40-59, and ≥60 years, respectively). HR was significantly higher for late-onset UC (≥60 years) than for early-onset UC (0-19 years). The long duration of 5-aminosalicylic acid use had a significantly low HR, with reference to the 1st quartile. CONCLUSIONS: The risk of CRC varies with age and sex in Korean patients with UC during the first decade after diagnosis. Early-onset UC (<40 years) increases the CRC risk.

Incidence and survival rates of lymphoepithelioma-like gastric carcinoma: analysis of the Korea Central Cancer Registry Database.

BACKGROUND: Lymphoepithelial carcinoma of the stomach (LEGC) is a rare type of gastric carcinoma. There is a limited understanding of the incidence and survival rates of LEGC. The aim was to investigate the nationwide incidence and survival rates of LEGC in Korea using the Korea Central Cancer Registry. METHODS: The data on LEGC were retrieved from the Korea Central Cancer Registry of Korean Cancer Center. The age and sex of the patients and the Surveillance, Epidemiology, and End Results (SEER) summary stage of the tumor were analyzed, and the relative survival rates (RSRs) were calculated. The Korea Central Cancer Registry has data of patients with LEGC from 1993 to 2017 but is approved to use personal information only from 2006 to 2017 due to privacy restrictions of the institute. The RSRs, as calculated data, were able to be disclosed from 1993 to 2017. RESULTS: Between 2006 and 2017, the total number of LEGC was 1,030, and the trend of incidence increased ty time (p = .002). In the SEER stage, the proportion of localized stage was 54.3% in 2006, and 73.9% in 2017, which increased from 2006 to 2017 significantly (p = .002). The RSR was higher in men than in women. The cumulative 5-year RSRs were 98.0% in the localized stage and 88.0% in the regional stage during 1993-2017. The 5-year RSRs increased 79.5% in 1996-2000 to 93.4% in 2013-2017. CONCLUSIONS: The incidence of LEGC is low, which has been increasing in recent years in South Korea. The prognosis of LEGC is good even at advanced stages and gets better as time goes by. Our findings provide useful insights to clinicians about LEGC and inform patients about the survival rate.

Colonoscopy Versus Fecal Immunochemical Test for Reducing Colorectal Cancer Risk: A Population-Based Case-Control Study.

INTRODUCTION: Use of colonoscopy or the fecal immunochemical test (FIT) for colorectal cancer (CRC) prevention is supported by previous studies. However, there is little specific evidence regarding comparative effectiveness of colonoscopy or FIT for reducing CRC risk. In this study, we compared the association of CRC risk with colonoscopy and FIT using a nationwide database. METHODS: This population-based case-control study used colonoscopy and FIT claims data from the Korean National Health Insurance System from 2002 to 2013. Data were analyzed from 61,221 patients with newly diagnosed CRC (case group) and 306,099 individuals without CRC (control group). Multivariable logistic regression models were used to evaluate the association between CRC and colonoscopy or FIT. RESULTS: Colonoscopy was associated with a reduced subsequent CRC risk (adjusted odds ratio [OR] 0.29). Stronger associations were found between colonoscopy and distal CRC, compared with proximal CRC (0.24 vs 0.47). In an analysis stratified by sex, the association was weaker in female subjects compared with male subjects (0.33 vs 0.27). Any FIT exposure was associated with CRC risk with an OR of 0.74; this association was stronger for distal cancer. As the frequency of cumulative FIT assessments increased (from 1 to ≥5), the OR of FIT exposure for CRC gradually decreased from 0.81 to 0.45. DISCUSSION: The association of colonoscopy or FIT with reduced CRC risk was stronger for distal CRC than for proximal CRC. FIT showed less CRC risk reduction than colonoscopy. However, as the frequency of cumulative FIT assessments increased, the association with CRC prevention became stronger.

Effect of Thiopurine on Potential Surgical Intervention in Crohn's Disease in Korea: Results from the CONNECT Study

Objectives: The incidence of Crohn's disease and the number of associated surgeries are increasing in Korea. This study investigated the effect of azathioprine/6-mercaptopurine (6-MP) and TNF-α antagonists on abdominal and perianal surgery in Korean patients with Crohn's disease. Design: A retrospective cohort study. Setting: Data from the Crohn's Disease Clinical Network and Cohort (CONNECT) were used. Patients with confirmed Crohn's disease between 1982 and 2008 from 32 hospitals in the Republic of Korea were enrolled. The effect of azathioprine/6-MP on abdominal and perianal surgery was analysed using logistic regression analysis adjusting for age and sex. Participants: In total, 1161 Crohn's disease patients were included in the Republic of Korea in the surgery (n = 462, male = 339, female = 123) and control groups (n = 699, male = 484, female = 215). Results: In total, 1161 patients were selected, with 462 patients who underwent abdominal (n = 245) or perianal surgery (n = 217). The preoperative usage rates of azathioprine/6-MP were 18.8% and 65.1% (p < 0.0001) in the surgery and control groups, respectively. The preoperative usage rates of TNF-α antagonists were 7.1% and 23.3% (p < 0.0001) in the surgery and control groups, respectively. A multivariate analysis revealed that the preoperative use of azathioprine/6-MP had an odds ratio of 0.094 for all surgeries (95% confidence interval [CI]: 0.070-0.127, p < 0.0001), 0.131 for abdominal surgery (95% CI: 397-1.599, p < 0.0001), and 0.059 for perianal surgery (95% CI: 0.038-0.091, p < 0.0001). The preoperative use of TNF-α antagonists had an odds ratio of 0.225 for all surgeries (95% CI: 0.151-0.335, p < 0.0001), 0.403 for abdominal surgery (95% CI: 0.261-0.623, p < 0.0001), and 0.064 for perianal surgery (95% CI: 0.026-0.160, p < 0.001). Strengths of this study: The study presents new evidence of the reduced risk of surgery following azathioprine use in Crohn's disease patients. Limitations of this study (1) This was not a controlled prospective study. (2) There was a selection bias specific to the CONNECT cohort. (3) The combination or sequential use of azathioprine/6-MP and TNF-α antagonists was not excluded. Conclusion: Azathioprine/6-MP is significantly associated with a reduced risk of abdominal and perianal surgery in Korean patients with Crohn's disease.

Trends of Incidence and Survival Rates of Mucosa-associated Lymphoid Tissue Lymphoma in the Korean Population: Analysis of the Korea Central Cancer Registry Database.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) is an extranodal lymphoma that occurs at various sites in the body. There is a limited understanding of the incidence and survival rates of MALT-lymphoma. To investigate the nation-wide incidence and survival rates of MALT-lymphoma in Korea during 1999-2017, the data on MALT-lymphoma were retrieved from the Korea Central Cancer Registry. METHODS: During the time period of 1999-2017, 11,128 patients were diagnosed with MALT-lymphoma. The age and sex of the patients and the Surveillance, Epidemiology, and End Results (SEER) summary stage of the tumor were analyzed, and the relative survival rates (RSRs) were calculated. RESULTS: The age-standardized incidence rates of MALT-lymphoma in 2017 among males and females were 1.53 and 1.61 per 100,000 individuals, respectively, whereas those in 1999 among males and females were 0.21 and 0.20, respectively in Korea. The RSRs were more than 97% at 10 years post-diagnosis between 1993 and 2017. The 5-year RSRs were 87.4%, 94.8%, 97.8%, and 98.6% during 1996-2000, 2001-2005, 2006-2010, and 2013-2017, respectively. Based on SEER summary staging, the 5-year RSRs during 2013-2017 were 100.3%, 90.8%, 91.3%, and 97.9% for patients with localized, regional, distant, and unknown stages of MALT-lymphoma, respectively. CONCLUSION: Although the incidence of MALT-lymphoma is low in Korea, it has been increasing in recent years. The prognosis of MALT-lymphoma is good even at advanced stages. These findings provide useful insights to clinicians about MALT-lymphoma and inform patients about the survival rate.

Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells Ameliorate Dextran Sodium Sulfate-Induced Chronic Colitis in Mice.

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), was decreased, but that of CD11b, IL-10, and transforming growth factor-ß (TGF-ß) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-α, and IFN-γ decreased, but that of IL-10, TGF-ß, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

Hot snare polypectomy with or without saline solution/epinephrine lift for the complete resection of small colorectal polyps.

BACKGROUND AND AIMS: The criteria for a standard polypectomy technique for complete removal of small colorectal polyps has not yet been established. This study aimed to compare the complete resection rate of hot snare polypectomy (HSP) with that of EMR for small, sessile, or flat polyps. METHODS: Patients with 5- to 9-mm non-pedunculated colorectal polyps were prospectively randomized to the HSP or EMR group. The presence of residual polyps was assessed by performing histologic assessment of 4-quadrant forceps biopsy specimens taken from the edges of the polypectomy site. The primary outcome was the complete resection rate after HSP or EMR; the secondary outcomes were the proportion of procedure-related adverse events and specimen-loss rate. Sample size was estimated using a superiority trial design. We assumed that the complete resection rate of the EMR group would be at least 8% higher than that of the HSP group. RESULTS: A total of 382 polyps in 269 patients were assessed and randomly assigned to each method using 4 × 4 block randomization. Of these, 353 polyps were finally analyzed based on the pathology results. The mean polyp size was 6.3 ± 1.3 mm. The complete resection rate did not differ between the HSP and EMR groups (88.4% [152/172] vs 92.8% [168/181], respectively; P = .2). The intraprocedural bleeding rate, immediately after polypectomy, was significantly higher in the HSP group than in the EMR group (5.2% vs 0.6%, respectively; P = .009). However, clinically significant bleeding and tissue retrieval failure rates did not differ between the groups. In the multivariate logistic regression analysis, sessile serrated adenoma/polyps or hyperplastic polyps were almost 3 times (odds ratio, 2.824; 95% confidence interval, 1.03-7.75; P = .044) more likely to be incompletely resected compared with other conventional adenomatous polyps. Except for pathology, we found no significant independent predictors for incomplete resection. CONCLUSION: EMR for small non-pedunculated colorectal polyps is not superior to HSP in terms of complete resection or safety. Both methods can be performed according to the endoscopist's preference. (Clinical trial registration number: KCT0001640; cris.nih.go.kr.).

Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells.

Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44+CD24+ESA+ pancreatic CSCs. PAUF knockdown (shPAUF) CFPAC-1 diminished the number of spheres and decreased stemness genes and CSC surface markers (CD133, c-MET and ALDH1). In addition, siPAUF CFPAC-1 decreased the mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control (p<0.05). In conclusion, PAUF was increased in pancreatic CSCs and the suppression of PAUF enhances chemotherapeutic response to gemcitabine and 5FU by decreasing MRP5 and RRM2 in pancreatic cancer cells.

Sorafenib inhibits 5-fluorouracil-resistant gastric cancer cell growth.

BACKGROUND: Sorafenib is a multi-kinase inhibitor used in the treatment of various cancers. This study investigated the inhibitory effect of sorafenib on xenograft models of gastric cancer cells and 5-fluorouracil (5-FU)-resistant cells. METHODS: The half-maximal inhibitory concentration (IC50) of sorafenib in NCI-N87 cells was determined. Xenograft models were established using BALB/c nude mice and were divided into four groups treated with vehicle, sorafenib (20 mg kg-1 day-1), 5-FU (50 mg kg-1 week-1), or a combination of sorafenib (20 mg kg-1 day-1) plus 5-FU (50 mg kg-1 week-1). 5-FU-resistant NCI-N87 cells were established by repeated exposure to 5-FU. RESULTS: Sorafenib inhibited NCI-N87 cell growth in a concentration-dependent manner with a mean IC50 of 16.345 ± 5.391 µM. Phosphorylation levels of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase in these cells decreased in a dose-dependent manner after exposure to sorafenib. Sorafenib induced the activation of caspase-3, and its combination with 5-FU more effectively inhibited the growth of xenograft tumors than either sorafenib or 5-FU alone (p < 0.05). Sorafenib markedly inhibited 5-FU-resistant NCI-N87 cell growth as well as sphere formation in both parental and 5-FU-resistant NCI-N87 cells. CONCLUSIONS: The sorafenib and 5-FU combination exhibited enhanced antitumor effects in a gastric cancer xenograft model and inhibited 5-FU-resistant cell proliferation and sphere formation. These findings suggest that sorafenib is useful in overcoming gastric cancer resistance to conventional chemotherapy.

Molecular characteristics of colorectal serrated polyps and hyperplastic polyps: A STROBE compliant article.

The serrated neoplasia pathway of colorectal carcinogenesis is characterized by BRAF mutation and aberrant DNA methylation, which have not been reported on Korean patients. The aim of this study was to investigate BRAF mutation and DNA methylation in colorectal serrated polyps and the right colon.Between 2005 and 2013, 146 colon polyps (47 tubular adenomas [TAs], 53 traditional serrated adenomas [TSAs], 17 sessile serrated adenomas/polyps [SSAs], and 29 hyperplastic polyps in the proximal colon [PHPs]) were collected from patients. Paraffin-embedded colon polyp tissue was used for DNA extraction. BRAF V600E mutation was identified through polymerase chain reaction (PCR) and pyrosequencing assay. The methylation status of the long interspersed nucleotide element-1, insulin-like growth factor binding protein 7 (IGFBP7), mutL homolog 1 (hMLH1), and CD133 genes were evaluated through disulfite conversion, PCR, and pyrosequencing assay.BRAF V600E mutation was found in 2.1% of TAs, 47.2% of TSAs, 41.2% of SSAs, and 20.7% of PHPs. TSA and SSA had higher BRAF mutation rates than did TA (P < 0.0001). TSA had higher BRAF mutation rates than did PHP (P = 0.018). IGFBP7 hypermethylation was found in 17% of TAs, 37.7% of TSAs, 88.2% of SSAs, and 37.5% of PHPs. TSA and SSA had higher hypermethylation of IGFBP7 than did TA (P = 0.021 and P < 0.0001, respectively). SSA had higher hypermethylation of IGFBP7 than did PHP (P = 0.002). hMLH1 hypermethylation was found in 2.1% of TAs, 5.7% of TSAs, 0% of SSAs, and 0% of PHPs. CD133 hypermethylation was found in 21.3% of TAs, 9.4% of TSAs, 35.3% of SSAs, and 17.4% of PHPs.BRAF mutation and methylation in TSA and SSA are different from those in PHP in Koreans. These findings suggested that PHP may have different molecular characteristics compared with other serrated polyps.

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer.

PURPOSE: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer. METHODS: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography. RESULTS: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively. CONCLUSIONS: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.