Long-term oncologic outcome of D3 lymph node dissection for clinical stage 2/3 right-sided colon cancer.

PURPOSE: To investigate oncologic outcomes including overall survival and disease-free survival depending on the extent of lymphadenectomy (D3 versus D2) by comparing D3 and D2 lymphadenectomy in patients with clinical stage 2/3 right colon cancer. METHODS: Consecutive series of patients who underwent radical resection for right colon cancer at our three hospitals between January 2015 and June 2018 were retrospectively analyzed. Study cohorts were divided into two groups: D3 group and D2 group. Oncologic, pathologic, and perioperative outcomes of the two groups were compared. RESULTS: A total of 295 patients (167 in the D2 group and 128 in the D3 group) were included in this study. Patients' characteristics showed no significant difference between the two groups. The median number of harvested lymph nodes was significantly higher in the D3 group than in the D2 group. The rate of complications was not significantly different between the two groups except for chyle leakage, which was more frequent in the D3 group. Five-year disease-free survival was 90.2% (95% CI: 84.8-95.9%) in the D3 group, which was significantly (p = 0.028) higher than that (80.5%, 95% CI: 74-87.5%) in the D2 group. There was no significant difference in overall survival between the two groups. CONCLUSION: Our results indicate that D3 lymphadenectomy is associated with more favorable 5-year disease-free survival than D2 lymphadenectomy for patients with stage 2/3 right-sided colon cancer. D3 lymphadenectomy might improve oncologic outcomes in consideration of the recurrence rate.

Short-term benefits of balneotherapy for patients with chronic pelvic pain: a pilot study in Korea.

The aim of this study was to evaluate whether balneotherapy might be effective in patients with chronic pelvic pain (CPP) in the short term. This was an open and prospective pilot study. The balneotherapy programme was performed in a spa resort located in Wando Island, Republic of Korea from August 26 2018 to September 1 2018. It consisted of 10 heated seawater baths (38 °C, 20 minutes) and 10 mud-pack applications (40 °C, 10 minutes) for five days. Sixteen patients were enrolled. Upon analysing responses from a patient questionnaire, we found improvement in parameters such as pain, bladder irrigation symptoms and quality of life after balneotherapy. Inflammatory marker IL-1 and TNF-α was significantly decreased after treatment compared to baseline. There were no adverse events during treatment. Our data suggest that five-day balneotherapy can be beneficial for patients with CPP in the short term.Impact statementWhat is already known on this subject? The majority of articles in the field of balneotherapy discuss the treatment of rheumatic or dermatological disease. However, data on the effectiveness of balneotherapy for chronic pelvic pain are very limited.What the results of this study add? Our study suggests that balneotherapy can be beneficial for patients with CPP in the short-term. The duration of balneotherapy was five days, which is shorter than that of the European studies. Intuitively, it may be doubtful whether short-term therapy has any practical effect. As most people living in Korea have a vacation period of about one week each in summer and winter, the choice of a five-day programme in our study reflects the reality of vacation schedules.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to demonstrate the persistence of these benefits on the long term, as well as their existence in appropriate control group and different duration of treatment.

Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer.

BACKGROUND: FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. METHODS: Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. RESULTS: Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). CONCLUSIONS: Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates.

Transanal Minimally Invasive Surgery (TAMIS) for Rectal Lesions: A Systematic Review.

BACKGROUND/AIMS: Transanal minimally invasive surgery (TAMIS) has received attention as an alternative to transanal endoscopic microsurgery for rectal lesions. We review the effectiveness and safety of TAMIS for the treatment of rectal lesions. METHODOLOGY: The MEDLINE, Web of Science, and Cochrane Library databases were searched using predefined inclusion criteria. The primary outcomes were positive margin rate, recurrence rate, conversion rate, range of applications, and complication rates. To derive pooled estimates of proportions with 95% Confidence Interval (CI) for the outcomes, a random effect model was used. RESULTS: Twelve studies including 155 patients were identified. The weighted mean size of rectal lesions was 3.3 cm (range 0.2-10 cm) and the weighted mean distance from the anal verge was 7.4 cm (range 0-20 cm). Six studies enrolled only the patients with low and mid rectal lesions mainly to avoid peritoneal entrance during excision. CONCLUSIONS: Based on the evidence from this limited number of studies, TAMIS appears to be an effective and safe treatment for rec tal lesions. However, the clinical outcome of TAMIS according to the location of the rectal lesions needs to be clarified. Comparison with other established surgical treatments are also mandatory.

Microfluidic-Generated Injectable Bulking Agents with Biocompatible Surfaces and Their Mid-term Outcomes in a Rat Model with Anal Sphincter Injury.

Bulking agents have gained attention as new, minimally invasive treatments for fecal incontinence. Various materials and surface treatment techniques have been extensively studied to ensure good biocompatibility and long-term stability. Despite significant improvements in biocompatibility, the nonuniform particle size of existing materials has led to other challenges, such as the induction of phagocytosis or reduction of injectability during in vivo tests. This study aimed to conduct a preclinical test of the midterm stability of bulking agents with newly formulated particles with uniform size. To this end, the particles were fabricated using microfluidics, resulting in a narrow size dispersity of less than 5% as the coefficient of variation, which is essentially distinct from conventional bulking agents. The microfluidic fabrication resulted in uniformly sized particles larger than the in vivo migratory limit of 80 µm and in a reduction in maximum injection pressure. Histological staining and microscopic observations confirmed proper positioning of the filler materials in vivo and a negligible immune response for up to 6 months, indicating successful midterm stability.

The efficacy of oral tegafur-uracil as maintenance therapy following intravenous 5-fluorouracil chemotherapy in stage III colon cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact on disease-free survival (DFS) of adding oral tegafur-uracil (UFT) to intravenous 5-fluorouracil (5-FU) as surgical adjuvant chemotherapy for stage II and III colon cancer. METHODOLOGY: The authors retrospectively analyzed 148 patients treated from 2000 through 2005 with pathologically confirmed stage II or III colon cancer. Forty seven patients were treated with 6 cycles of 5-FU+leucovorin (5-FU group) and the other 101 patients were treated with same above regimen followed by an additional 12 cycles of UFT+leucovorin (LV) for 28 days with a 7-day rest period (5-FU+UFT group). RESULTS: The median follow-up time was 64.9 months (range 15.3-95.2 months) and mean age was 58.8±10.8. The clinical characteristics of the 5-FU+UFT and 5-FU groups were similar. Furthermore, for all study subjects and stage II patients, 3-year DFS rates were not significantly different between two groups. However, for stage III patients, 3-year DFS rates were 80.0% and 60.7% in the 5-FU+UFT and 5-FU groups, respectively (HR=0.32; p=0.01; 95% CI=0.13-0.76). CONCLUSIONS: The addition of UFT to 5-FU was found that significantly improve DFS in patients with stage III colon cancer. The authors cautiously suggest UFT as a maintenance therapy following 5-FU chemotherapy could be another option in stage III colon cancer patients.

Injectable polydimethylsiloxane microfiller coated with zwitterionic polymer for enhanced biocompatibility.

Silicone-based fillers have been applied in several branches of medicine, such as soft tissue augmentation, because of their stability and durability. However, the inherently hydrophobic surfaces of silicone occasionally cause excessive deposition of the fibrous matrix in vivo, leading to severe fibrosis. In this study, we evaluated the use of a zwitterionic copolymer to offer a facile surface treatment method for silicone-based fillers and performed a preclinical trial of the formulation as-prepared. The copolymer has amphiphilic moieties, which act as macromolecular surfactants that can functionalize and stabilize the silicone particles during fabrication. The effectiveness and safety of the particle filler were evaluated histologically by scoring the peri-implant tissues into previously defined categories. Our results suggest that zwitterion-coated silicone fillers can inhibit protein adsorption, and thus, help attenuate foreign body reactions in a rat model. This demonstrates their potential for wide application in different fields within the discipline of medicine.

Preclinical testing of an anal bulking agent coated with a zwitterionic polymer in a fecal incontinence rat model.

Fecal incontinence is a disabling condition in which the passage of fecal material cannot be controlled. Although the condition is not life-threatening, it can seriously reduce the quality of life of a patient by isolating them from others. Though various surgical treatments are available for moderate to severe symptoms, a bulking agent is a minimally invasive technique that has attracted attention because of its safety and simple treatment process. However, the biocompatibility of bulking agent materials remains a central issue, with their durability questioned because immune responses and/or the circulatory system may remove the bulking agent in vivo. This study investigated a bulking agent composed of polydimethylsiloxane and hyaluronic acid as a microfiller and carrier gel, respectively. To improve the injectability of the bulking agent, the filler size was tuned using a suspension-based fabrication technique. To evade immune responses, the filler surface was treated with a zwitterionic polymer that simultaneously functionalized and stabilized the material interfaces. The resulting bulking agent exhibited good injectability and biocompatibility in vitro, with 58% lower protein adsorption and no cytotoxicity, leading to an improved bulking effect in a preclinical rat model compared with a bulking agent without surface treatment. These results illustrate the promising potential of bulking agents as a therapy for fecal incontinence with reduced foreign body reactions and long-lasting efficacy.

Clinical outcomes of surgical management for recurrent rectal prolapse: a multicenter retrospective study.

Purpose: There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. Methods: We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. Results: A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2-129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. Conclusion: For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

Lymph node ratio as determined by the 7th edition of the American Joint Committee on Cancer staging system predicts survival in stage III colon cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the prognostic usefulness of the lymph node ratio (LNR) in stage III colon cancer using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. METHOD: We analyzed data from 130 consecutive patients with stage III colon cancer. Kaplan-Meier and Cox proportional hazard model analyses were used to evaluate prognostic effects. RESULTS: Quartile analysis indicated that an LNR of 0.1638 was the best cut-off value with regard to predicting disease-free survival (DFS). Six patients had stage IIIA disease, 102 patients had stage IIIB disease, and 22 patients had stage IIIC disease. For patients with stage IIIB disease, the 3-year DFS for an LNR of <0.1638 (N = 87) and an LNR of ≥0.1638 (N = 15) was 79.0% and 50.0%, respectively (P = 0.015). For patients with stage IIIC disease, the 3-year DFS for an LNR of <0.1638 (N = 6) and an LNR of ≥0.1638 (N = 16) was 100% and 28.6%, respectively (P = 0.03). CONCLUSIONS: The authors found that 7th AJCC stage IIIB and stage IIIC patients are heterogeneous groups with respect to DFS, when stratified by LNR, and suggest that an LNR-based algorithm be devised for incorporation into the 7th AJCC staging system.

Comparison between laparoscopy and noninvasive tests for the diagnosis of tuberculous peritonitis.

BACKGROUND: Despite recent progress, the fast and accurate diagnosis of tuberculous peritonitis (TBP) continues to be a challenge, mainly because of the lack of specific clinical features and the difficulty in isolating the M. tuberculosis. The present study aimed to investigate the role of laparoscopy in the diagnosis of TBP, compared to noninvasive tests. METHODS: We retrospectively studied 60 patients who had diagnostic laparoscopy for suspected TBP between January 2002 and June 2010. RESULTS: Forty-one patients were diagnosed with TBP. In terms of accuracy and predictive value, the visual diagnosis via laparoscope was the most diagnostic test. In the noninvasive tests, both the ascitic adenosine deaminase (ADA) level over 30 U/l, and the ascitic lactate dehydrogenase (LDH) level over 90 U/l had relatively high positive, as well as negative, predictive values. The overall morbidity and mortality rates for laparoscopy were 5 and 5%, respectively. CONCLUSIONS: Laparoscopy is a rapid and accurate diagnostic test for TBP. However, complications may occur. In older patients with associated conditions, a combination of various noninvasive tests and empirical treatments is needed prior to laparoscopy.

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

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

Impact of D3 lymph node dissection on upstaging and short-term survival in clinical stage I right-sided colon cancer.

BACKGROUND: D3 lymph node dissection is becoming the standard procedure for the treatment of advanced right colon cancer and has shown increasing evidence of its oncologic benefit. However, a clear indication for its application is lacking and data on this topic is unsatisfactory. Thus, the necessity for D3 lymph node dissection in clinical stage I right colon cancer remains controversial. METHODS: We retrospectively analyzed data from clinical stage I right colon cancer patients who underwent radical surgery at three hospitals of Korea university medical center between January 2015 and June 2018. We compared surgical complications and short-term oncologic outcomes between D2 and D3 lymph node dissections in these patients. RESULTS: Among 512 patients, 122 (23.8%) were clinical stage I. Of these, 88 and 34 patients received D2 and D3 lymph node dissection, respectively. There were no statistically significant differences in clinicopathologic variables and surgical outcomes between the two groups. Upstaging occurred in 16 patients (47.1%) in the D3 group and 23 patients (26.1%) in the D2 group. There were four recurrences in the D2 group but no recurrence in the D3 group. Log-rank tests showed no statistically significant difference in disease-free survival rates between the two groups (p = 0.210). CONCLUSION: There was no significant difference in disease-free survival rates between D2 and D3 lymph node dissection in clinical stage I right colon cancer patients. However, recurrence occurred in the D2 group. Efforts to improve the accuracy of clinical staging are required and more studies with better quality are needed.

Lymph Node Micrometastasis Cannot Be Considered as Positive Lymph Node in Nonmetastatic Colorectal Cancer.

The prognostic value of micrometastasis in colorectal cancer (CRC) remains controversial. The study investigated whether lymph node (LN) micrometastasis can have prognostic value in CRC as compared with macrometastasis. The study included 488 patients with curatively resected stage I, II, or III CRC treated between 2004 and 2011. Immuohistochemical staining with monoclonal antibody CAM 5.2 was performed on negative LNs by hematoxylin-eosin staining. The prognostic value of LN micrometastasis was investigated in multivariate analysis. Regression analysis was performed to identify a causal relationship between micro- and macrometastasis. Survival differences were compared between conventional N staging and hypothetic N staging taking micrometastasis in the positive node. A total of 93 patients (19.1%) showed LN micrometastasis. Patients with micrometastasis had more advanced tumor characteristics in terms of tumor size, grade, T stage, N stage, lymphatic invasion, and vascular invasion. In multivariate analysis, micrometastasis was not related with recurrence. Preoperative carcinoembryonic antigen level, neural invasion, and macrometastasis were independent risk factors in the analysis. Regression analysis showed that there was not a causal relationship between micro- and macrometastasis (R2 = 0.004, P = 0.153). When the cumulative numbers of micro- and macrometastatic LNs were calculated together, the discriminative power of survival difference between each node stage became less prominent, compared with conventional N staging. LN micrometastasis is related with advanced tumor characteristics, but does not reflect poor prognosis in nonmetastatic CRC. Micrometastasis cannot be considered as positive LN to predict poor prognosis.

Eosinophilic Gastrointestinal Disorder Presenting as Intractable Vomiting and Ascites in a Young Girl.

Eosinophilic gastrointestinal disorder (EGID) is a rare disease in children that affects the bowel wall, with eosinophilic infiltration in the absence of any other causes for eosinophilia. The etiology remains unknown, but allergies and immunological imbalance are suspected triggers. We encountered a case of serosal EGID presenting as intractable vomiting and ascites in a 9-year-old girl, after influenza virus infection. Peripheral eosinophilia was not present. The diagnosis was confirmed by biopsy of the bowel wall through laparotomy and endoscopy, and controlled by 2 courses of steroid therapy due to recurring symptoms. Influenza virus infection was assumed to play a role in the onset of EGID through a Th2 response that stimulated eosinophilic infiltration in the GI tract. We therefore report this case along with a literature review.

Clinical Significance of 5-Fluorouracil Chemosensitivity Testing in Patients with Colorectal Cancer.

AIM: To evaluate whether the results of chemosensitivity testing were associated with prognosis of colorectal cancer patients after adjuvant 5-fluorouracil (FU)/ leucovorin chemotherapy. PATIENTS AND METHODS: Eighty-nine patients who received 5-FU/leucovorin adjuvant chemotherapy for colorectal cancer were enrolled. Chemosensitivity tests were performed and tumor growth inhibition rate was calculated using the MTT (3-(4,5-dimethylthiazol-2-yl)02,5-diphenyl-2H tetrazolium bromide) assay. RESULTS: Fifty-one patients (57.3%) were sensitive to 5-FU according to the chemosensitivity test. After a median follow-up of 64 months, there was a significant difference between the 5-year disease-free survival rates of the chemo-sensitive and chemo-resistant groups. However, there was no significant difference in the overall 5-year survival between the chemo-sensitive and chemo-resistant groups. CONCLUSION: A positive 5-FU sensitivity test with in vitro histoculture drug response assay (HDRA) was associated with better disease-free survival. Chemosensitivity may be a prognostic factor for colorectal cancer patients undergoing adjuvant 5-FU/leucovorin chemotherapy.

Endoscopic obstruction in rectal cancers: survival and recurrence patterns following curative surgery.

BACKGROUND: It is controversial whether preoperative obstruction in rectal cancers can affect prognosis or influence recurrence patterns. We investigated the association between endoscopic obstruction with survival and recurrence patterns in patients with locally advanced rectal cancers. MATERIALS AND METHODS: An observational study and multivariate analysis were conducted to identify determinants of survival and to compare recurrence patterns between patients with obstructive or nonobstructive tumors after curative resection. Endoscopic obstruction was defined as a luminal obstruction of the rectum severe enough to prevent the colonoscope from passing beyond the tumor. RESULTS: Cancer was obstructive in 91 patients (16.8%) and nonobstructive in 452 (83.2%). Median follow-up was 50 (range, 3-161) months. Local recurrence occurred in 17 patients (14 nonobstructed [5.4%] and 3obstructed [5.5%]; P=1.0) and systemic recurrence in 83 (62 nonobstructed [23.8%] and 21 obstructed [38.2%]; P=.042]). Endoscopic obstruction was a significant prognostic factor in stage III rectal cancers (P=.001) but not in stage II tumors. The multivariate analysis showed that endoscopic obstruction was an independent prognostic factor for overall survival, but not for disease-free survival, in patients with stage III rectal cancers. Endoscopic obstruction was associated with multiple-site systemic recurrence that was unsalvageable (salvageable surgery, 24 nonobstructed [40%] and 2 obstructed [10%]; P=.014). CONCLUSIONS: Endoscopic obstruction in patients with stage III rectal cancer predicted worse overall survival and was associated with multiple-site systemic recurrence.

Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer.

The homeodomain transcription factor CDX2 directs development and maintenance of normal intestinal epithelium. However, the role of CDX2 in colorectal carcinogenesis is poorly understood. Hence, we investigated the CDX2 expression in patients with colorectal cancer and its relationship to tumor cell proliferation and differentiation and evaluated the role of this molecule as a biologic marker for the prediction of poor patient survival. We retrospectively reviewed 207 patients with colorectal cancer, with an available paraffin block, who underwent surgical resection between January 2002 and December 2004 at Korea University Guro Hospital. CDX2 expression was compared between tumor tissue and the adjacent normal mucosa using immunohistochemistry and Western blot analysis. Immunohistochemical staining for CDX2, Ki-67, and CK20 was performed in each tumor tissue. Immunohistochemistry revealed that CDX2 protein is overexpressed by colorectal cancer compared with adjacent normal mucosa (P < 0.001). In the Western blot analysis, tumor tissue showed a trend toward overexpression of CDX2 protein compared with normal mucosa (P = 0.09). CDX2 expression showed a significant direct correlation with the expression of Ki-67 and CK20 in tumor tissue (P = 0.028 and P = 0.042, respectively). Survival analysis showed that reduced CDX2 expression was statistically and significantly related to poor overall survival. Reduced CDX2 expression is associated with poor overall survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

Expression of GLI1 correlates with expression of lymphangiogenesis proteins, vascular endothelial growth factor C and vascular endothelial growth factor receptor 3, in colorectal cancer.

Aberrant activation of the hedgehog (Hh) signaling pathway is associated with tumorigenesis in various tissues. In colorectal cancer (CRC), evidence for Hh activation is inconsistent, and the relationship between the Hh signaling pathway and lymphangiogenesis has not been studied. The aim of this study was to determine the relationship between Hh signaling and lymphangiogenesis and the association of this relationship with lymph node metastasis in CRC. We investigated 189 patients who underwent curative surgical resection for CRC between 2002 and 2004 at Korea University Guro Hospital. Paraffin-embedded specimens of colorectal adenocarcinoma and adjacent normal mucosa were evaluated. Immunohistochemical staining for Sonic hedgehog (Shh), Gli1, vascular endothelial growth factor C (VEGFC), and VEGF receptor 3 (VEGFR3) was performed for each specimen. Tumor specimen showed significantly strong staining of Shh, Gli1, VEGFC, and VEGFR3 compared with a normal specimen. Shh expression was not associated with Gli1 expression. Gli1 expression correlated positively with VEGFC and VEGFR3 expression (P < 0.05 in both) but not with lymph node metastasis. Activation of the Hh signaling pathway associated with Gli1 promotes expression of lymphangiogenesis proteins, VEGFC and VEGFR3, in CRC. Further studies are necessary to determine the association of this relationship with lymph node metastasis in CRC.

SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer.

BACKGROUND: Silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, might act as a tumor promoter by inhibiting p53, but may also as a tumor suppressor by inhibiting several oncogenes such as ß-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1. METHODS: Immunohistochemical expressions of SIRT1, DBC1, ß-catenin, surviving, and p53 were evaluated using 2 mm tumor cores from 349 colorectal cancer patients for tissue microarray. RESULTS: Overexpression of SIRT1, DBC1, survivin, and p53 was seen in 235 (67%), 183 (52%), 193 (55%), and 190 (54%) patients, respectively. Altered expression of ß-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of ß-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), ß-catenin (p=0.001), and survivin (p=0.002), but not with p53. On multivariate analysis, age, tumor stage, differentiation, and expression of SIRT1 were independent prognostic factors significantly associated with overall survival. CONCLUSIONS: SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with ß-catenin and survivin rather than p53.