Some colorectal cancer (CRC) patients present symptoms of bowel obstruction, which is considered a surgical emergency. Because of poor medical condition and high incidence of post-surgical complications, there has been increasing use of self-expanding metal stents (SEMS) for the purpose of palliation or as a bridge to surgery with some benefits, including shorter hospital stays, lower rates of adverse events, and one-stage surgery. However, with increasing survival of CRC patients, there have been controversial data on clinical outcomes and complications, compared between SEMS use and surgery for treatment of malignant bowel obstruction. We review recent clinical data on clinical outcomes of SEMS use compared to surgery, including complications.
Colon; Cancer; Obstruction; Stent; Palliation
Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, especially the heterogeneity of tumors. We need to target cells and processes that are critical to carcinogenesis for chemoprevention and treatment of advanced cancer. Recent research has shown that intestinal stem cells may serve an important role in tumor initiation and formation of cancer stem cells. Moreover, studies have shown that the tumor microenvironment may play additional roles in dedifferentiation, to enable tumor cells to take on stem cell features and promote the formation of tumorigenic stem cells. Therefore, early tumorigenic changes of stem cells and signals for dedifferentiation may be good targets for chemoprevention. In this review, I focus on cancer stem cells in colorectal carcinogenesis and the effect of major chemopreventive drugs on stem cell-related pathways.
Colorectal cancer; Chemoprevention; Cancer stem cell; Carcinogenesis; Microenvironment
With the significance of stable adhesion of alveolar bone and peri-implant soft tissue on the surface of titanium for successful dental implantation procedure, the purpose of this study was to apply microgrooves on the titanium surface and investigate their effects on peri-implant cells and tissues.
Three types of commercially pure titanium discs were prepared; machined-surface discs (A), sandblasted, large-grit, acid-etched (SLA)-treated discs (B), SLA and microgroove-formed discs (C). After surface topography of the discs was examined by confocal laser scanning electron microscopy, water contact angle and surface energy were measured. Human gingival fibroblasts (hGFs) and murine osteoblastic cells (MC3T3-E1) were seeded onto the titanium discs for immunofluorescence assay of adhesion proteins. Commercially pure titanium implants with microgrooves on the coronal microthreads design were inserted into the edentulous mandible of beagle dogs. After 2 weeks and 6 weeks of implant insertion, the animal subjects were euthanized to confirm peri-implant tissue healing pattern in histologic specimens.
Group C presented the lowest water contact angle (62.89±5.66 θ), highest surface energy (45±1.2 mN/m), and highest surface roughness (Ra=22.351±2.766 µm). The expression of adhesion molecules of hGFs and MC3T30E1 cells was prominent in group C. Titanium implants with microgrooves on the coronal portion showed firm adhesion to peri-implant soft tissue.
Microgrooves on the titanium surface promoted the adhesion of gingival fibroblasts and osteoblastic cells, as well as favorable peri-implant soft tissue sealing.
Cell adhesion; Dental implants; Titanium; Wound healing
We have developed a new method of segmenting the areas of absorbable implants and bone using region-based segmentation of micro-computed tomography (micro-CT) images, which allowed us to quantify volumetric bone-implant contact (VBIC) and volumetric absorption (VA).
Materials and Methods
The simple threshold technique generally used in micro-CT analysis cannot be used to segment the areas of absorbable implants and bone. Instead, a region-based segmentation method, a region-labeling method, and subsequent morphological operations were successively applied to micro-CT images. The three-dimensional VBIC and VA of the absorbable implant were then calculated over the entire volume of the implant. Two-dimensional (2D) bone-implant contact (BIC) and bone area (BA) were also measured based on the conventional histomorphometric method.
VA and VBIC increased significantly with as the healing period increased (p<0.05). VBIC values were significantly correlated with VA values (p<0.05) and with 2D BIC values (p<0.05).
It is possible to quantify VBIC and VA for absorbable implants using micro-CT analysis using a region-based segmentation method.
Absorbable Implants; Osseointegration; X-Ray Microtomography; Computer-Assisted Image Processing
AIM: To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease (IBD) patients.
METHODS: We obtained clinical data on Crohn’s disease (CD) (n = 691) and ulcerative colitis (n = 1113) from a tertiary referral medical center between 2005 and 2012. Seventeen patients (2.5%) with CD and 27 patients (2.4%) with ulcerative colitis (UC) were identified as having a familial history of IBD, including the first and second degree relatives. For each control case, three times the number of age-, sex-, and diagnosis year-matched CD and UC patients, without a family history of IBD, were randomly selected in this case control study.
RESULTS: There were no significant differences in age or main symptom at diagnosis, extraintestinal manifestation, location/extent, behavior of disease activity, number of hospitalizations, number of operations, operation type, number of relapses, or oral medical treatment between familial and sporadic CD and UC patients. Median (min-max) follow-up periods after diagnosis of familial CD and sporadic CD patients were 84 (24-312) and 36 (8-240) mo, respectively (P = 0.008). Familial CD patients more frequently used anti-tumor necrosis factor (TNF) antibodies compared to sporadic CD patients (17.6% vs 0%, P = 0.014).
CONCLUSION: In conclusion, a family history of IBD does not seem to be an important predictive factor affecting clinical characteristics or disease course even if there is a more frequent use of anti-TNF antibodies in familial CD patients compared to sporadic CD patients.
Inflammatory bowel disease; Family history; Crohn’s disease; Ulcerative colitis; Clinical characteristics
AIM: To evaluate the depth of invasion of small, early colorectal cancers (ECCs) using conventional endoscopic features.
METHODS: From January 2005 to September 2011, colonoscopy cohort showed that a total of 72 patients with small colorectal cancers with the size less than 20 mm underwent colonoscopy at the Yonsei University College of Medicine, Seoul, South Korea. Among them, 8 patients were excluded due to incomplete medical records. Finally, a total of 64 ECCs with submucosa (SM) invasion and size less than 20 mm were included. One hundred fifty-two adenomas with size less than 20 mm were included as controls. Nine endoscopic features, including seven morphological findings (i.e., loss of lobulation, excavation, demarcated and depressed areas, stalk swelling, fullness, fold convergence, and bleeding ulcers), pit patterns, and non-lifting signs, were evaluated retrospectively. All endoscopic features were evaluated by two experienced endoscopists who have each performed over 1000 colonoscopies annually for more than five years without knowledge of the histology.
RESULTS: Among the morphological findings, the size of deep submucosal cancers was bigger than that of superficial lesions (16.9 mm vs 12.3 mm, P < 0.001). Also, demarcated depressed areas, stalk swelling, and fullness were more common in deep SM cancers than in superficial tumors (demarcated depressed areas: 52.0% vs 15.7%, P < 0.001; stalk swelling: 100% vs 4.2%, P < 0.001; fullness: 25.0% vs 0%, P = 0.001). Among deep SM cancers, 96% of polyps showed invasive pit patterns, whereas 19.4% of superficial tumors showed invasive pit patterns (P < 0.001). A positive non-lifting sign was more common in deep SM cancers (85.0% vs 28.6%, P < 0.001). Diagnostic accuracy of invasive morphology, invasive pit patterns, and non-lifting signs for deep SM cancers were 71%, 82%, and 75%, respectively.
CONCLUSION: Conventional endoscopic findings were insufficient to discriminate small, deep SM cancers from superficial SM cancers by white light, standard colonoscopy.
Colonoscopy; Colorectal neoplasms; Differential diagnosis
This study evaluated the efficacy of alveolar ridge preservation methods with and without primary wound closure and the relationship between histometric and micro-computed tomographic (CT) data.
Materials and Methods
Porcine hydroxyapatite with polytetrafluoroethylene membrane was implanted into a canine extraction socket. The density of the total mineralized tissue, remaining hydroxyapatite, and new bone was analyzed by histometry and micro-CT. The statistical association between these methods was evaluated.
Histometry and micro-CT showed that the group which underwent alveolar preservation without primary wound closure had significantly higher new bone density than the group with primary wound closure (P<0.05). However, there was no significant association between the data from histometry and micro-CT analysis.
These results suggest that alveolar ridge preservation without primary wound closure enhanced new bone formation more effectively than that with primary wound closure. Further investigation is needed with respect to the comparison of histometry and micro-CT analysis.
Bone Substitutes; Polytetrafluoroethylene; X-Ray, Microtomography
AIM: To evaluate the clinicopathological features of colorectal cancer (CRC) with a v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and its molecular interaction with microsatellite instability (MSI) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in patients with advanced CRCs.
METHODS: From October 2009 to December 2011, 141 patients with stage III (n = 51) or IV (n = 90) CRCs who were tested for the BRAF mutation at Severance Hospital were included. Among 141 patients, five were excluded due to follow-up loss. Therefore, 136 patients were included in the study. The clinicopathological data, MSI status, and KRAS/BRAF mutation status were reviewed retrospectively. In addition, to evaluating the value of BRAF mutation status, progression-free survival and overall survival in all patients were collected and compared between the BRAF wild-type group and BRAF mutation group.
RESULTS: Of 136 patients, 80 (58.8%) were male and the mean age was 59 years. BRAF and KRAS mutations were detected in 9.6% and 35.3% of patients, respectively. Only 4.3% of patients had MSI-high tumors and there were no MSI-high in tumors with a BRAF mutation. BRAF mutations tended to be more frequent in stage IV than in stage III (11.76% vs 5.88%, P = 0.370). Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without (7.69% vs 38.21%, P = 0.033). Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis (P = 0.041) and multivariate analysis (HR = 2.195; 95%CI: 1.039-4.640; P = 0.039), while progression-free survival was not different according to BRAF mutation status.
CONCLUSION: CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.
BRAF; Colorectal cancer; Molecular features; Chemotherapy response; Prognosis
Objective. Layered double hydroxide (LDH) nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML), 5-FU/LDH (FL), and (MTX + 5-FU)/LDH (MFL) nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.
We have successfully prepared nanohybrids of biofunctional ferulic acid and layered double hydroxide nanomaterials through reconstruction and exfoliation-reassembly routes. From X-ray diffraction and infrared spectroscopy, both nanohybrids were determined to incorporate ferulic acid molecules in anionic form. Micrsocopic results showed that the nanohybrids had average particle size of 150 nm with plate-like morphology. As the two nanohybridization routes involved crystal disorder and random stacking of layers, the nanohybrids showed slight alteration in z-axis crystallinity and particle size. The zeta potential values of pristine and nanohybrids in deionized water were determined to be positive, while those in cell culture media shifted to negative values. According to the in vitro anticancer activity test on human cervical cancer HeLa cells, it was revealed that nanohybrids showed twice anticancer activity compared with ferulic acid itself. Therefore we could conclude that the nanohybrids of ferulic acid and layered double hydroxide had cellular delivery property of intercalated molecules on cancer cell lines.
Behçet’s disease (BD) is a chronic inflammatory disease affecting multiple organ systems, such as the skin, joints, blood vessels, central nervous system, and gastrointestinal tract. Intestinal BD is characterized by intestinal ulcerations and gastrointestinal symptoms. The medical treatment of intestinal BD includes corticosteroids and immunosupressants. There have been several reports of tumor necrosis factor-α (TNF-α) blockers being successful in treatment of refractory intestinal BD. Here, we report on a patient who was diagnosed with intestinal BD despite treatment with the fully humanized TNF-α blocker (adalimumab) for underlying ankylosing spondylitis. This patient achieved clinical remission and complete mucosal healing through the addition of a steroid and azathioprine to the adalimumab regimen.
Intestinal Behçet’s disease; Tumor necrosis factor-α; Adalimumab
An animal periodontitis model is essential for research on the pathogenesis and treatment of periodontal disease. In this study, we have introduced a lipopolysaccharide (LPS) of a periodontal pathogen to the alveolar bone defect of experimental animals and investigated its suitability as a periodontitis model.
Alveolar bone defects were made in both sides of the mandibular third premolar region of nine beagle dogs. Then, the animals were divided into the following groups: silk ligature tied on the cervical region of tooth group, Porphyromonas gingivalis LPS (P.g. LPS)-saturated collagen with silk ligature group, and no ligature or P.g. LPS application group as the control. The plaque index and gingival index were measured at 0 and 4 weeks postoperatively. The animals were then euthanized and prepared for histologic evaluation.
The silk ligature group and P.g. LPS with silk ligature group showed a significantly higher plaque index at 4 weeks compared to the control (P<0.05). No significant difference was found in the plaque index between the silk ligature group and P.g. LPS with silk ligature group. The P.g. LPS with silk ligature group showed a significantly higher gingival index compared to the silk ligature group or the control at 4 weeks (P<0.05). Histologic examination presented increased inflammatory cell infiltration in the gingival tissue and alveolar bone of the P.g. LPS with silk ligature group.
An additional P.g. LPS-saturated collagen with silk ligature ensured periodontal inflammation at 4 weeks. Therefore, P.g. LPS with silk ligature application to surgically created alveolar bone defects may be a candidate model for experimental periodontitis.
Animal models; Lipopolysaccharides; Periodontitis; Porphyromonas gingivalis
AIM: To increase satisfaction and diminish anxiety and shame during colonoscopy, we developed novel double pants (NDP) which consist of doubled fabrics with an inner hole. The aim of study was to compare satisfaction, anxiety and shame between NDP and conventional single pants (CSP).
METHODS: Total 160 consecutive examinees were randomly divided into NDP and CSP group. Before colonoscopy, questionnaires identifying state and trait anxiety were completed. After colonoscopy, questionnaires for overall satisfaction (Group Health Association of America 9) and pants-specific satisfaction (5-20), state anxiety (20-80), and shame (6-24) were interviewed.
RESULTS: Pants-specific satisfaction scores regarding willingness to repeat colonoscopy using same pants (3.3 ± 0.8 vs 2.1 ± 0.9, P < 0.001) and recommendation of same pants to other people (3.3 ± 0.7 vs 2.0 ± 1.0, P < 0.001) were significantly higher in NDP than CSP groups. State anxiety (33.0 ± 7.0 vs 35.4 ± 6.9, P = 0.028) and shame (6.6 ± 1.5 vs 8.1 ± 3.2, P = 0.001) after colonoscopy was lower in NDP group compared with CSP group.
CONCLUSION: The NDP contribute to increase satisfaction and decrease anxiety and shame after colonoscopy.
Pants; Colonoscopy; Satisfaction; Shame; Anxiety