Sang-Jeon Lee

Follow-up evaluation of the effect of vaginal delivery on the pelvic floor

PURPOSE: The aim of this study was to evaluate the effect of vaginal delivery on the pelvic floor by serial measurement of pudendal nerve terminal motor latency, perineal descent, and anal pressure before and after delivery. METHODS: Eighty pregnant females (40 primigravidae, 40 multigravidae) expecting vaginal delivery were prospectively evaluated. Measurements of pudendal nerve terminal motor latency, perineometry, and manometry were performed two to three months before delivery and two to three days, two months, and six months after delivery. RESULTS: Before delivery, pudendal nerve terminal motor latency showed no significant difference between primigravidae and multigravidae. Perineal plane at straining was lower and the descent was larger in multigravidae than primigravidae. Anal squeeze pressure was also lower in multigravidae than primigravidae. Two to three days after delivery, regardless of the group, pudendal nerve terminal motor latency was prolonged, perineal plane at straining became lower, the descent increased, and anal squeeze pressure decreased. Two months after delivery, pudendal nerve terminal motor latency recovered to the level before delivery. Perineal descent also recovered somewhat, but remained increased after six months had passed. In primiparae, perineal plane at straining remained lower after six months had passed. However, in multiparae the plane remained lower only for two months and recovered by six months postpartum. Anal squeeze pressure also showed a moderate recovery, but still remained significantly lower at six months postpartum. CONCLUSIONS: Pudendal nerve damage and functional impairment in the pelvic floor sphincter musculature occurs during vaginal delivery. Pudendal nerve terminal motor latency recovers after two months, whereas functional disturbance in the pelvic floor persists at least until six months.

Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients

Background/AimsEpithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients.MethodsWe evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR.ResultsLoss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation.ConclusionsThe combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9398289629244673

HDAC inhibitors induce epithelial-mesenchymal transition in colon carcinoma cells

The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various types of cancers. We investigated the EMT phenotype in four colon cancer cell lines when challenged with HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) with or without transforming growth factor-β1 (TGF-β1) treatment. Four colon cancer cell lines with different phenotypes in regards to tumorigenicity, microsatellite stability and DNA mutation were used. EMT phenotypes were assessed by the expression of E-cadherin and vimentin using western blot analysis, immunofluorescence, quantitative real-time RT-PCR following treatment with TSA (100 or 200 nM) or VPA (0.5 mM) with or without TGF-β1 (5 ng/ml) for 24 h. Biological EMT phenotypes were also evaluated by cell morphology, migration and invasion assays. TSA or VPA induced mesenchymal features in the colon carcinoma cells by a decrease in E-cadherin and an increase in vimentin expression at the mRNA and protein levels. Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of vimentin. These responses occurred after 6 h and increased until 24 h. Colon cancer cells changed from a round or rectangular shape to a spindle shape with increased migration and invasion ability following TSA or VPA treatment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). TSA or VPA induced a mesenchymal phenotype in the colon carcinoma cells and these effects were augmented in the presence of TGF-β1. HDAC inhibitors require careful caution before their application as new anticancer drugs for colon cancers.

A Case of Colovesical Fistula Induced by Sigmoid Diverticulitis

Colonic diverticulosis has continuously increased, noticeably left-sided diseases, in Korea. A colovesical fistula is an uncommon complication of diverticulitis, and its most common cause is diverticular disease. Confirmation of its presence generally depends on clinical findings, such as pneumaturia and fecaluria. The primary aim of a diagnostic workup is not to observe the fistular tract itself but to find the etiology of the disease so that an appropriate therapy can be initiated. We present here the case of a 79-year-old man complaining of pneumaturia and fecaluria. On abdomen and pelvis CT, the patient was diagnosed as having a colovesical fistula due to sigmoid diverticulitis. After division of the adhesion between the sigmoid colon and the bladder, the defect of the bladder wall was repaired by simple closure. The colonic defect was treated with a segmental resection, including the rectosigmoid junction. The patient is doing well at 6 months after the operation and shows no evidence of recurrence of the fistula.

Podoplanin, α-Smooth Muscle Actin or S100A4 Expressing Cancer-Associated Fibroblasts Are Associated with Different Prognosis in Colorectal Cancers

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), α-smooth muscle actin (α-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or α-SMA CAFs were detected in all the cases. PDPN/S100A4 and α-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/α-SMAhigh CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4high CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the α-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/α-SMAhigh or PDPN-/S100A4high CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.

Voltage-dependent Ca2+ Current Identified in Freshly Isolated Interstitial Cells of Cajal (ICC) of Guinea-pig Stomach

The properties of voltage dependent Ca(2+) current (VDCC) were investigated in interstitial cells of Cajal (ICC) distributed in the myenteric layer (ICC-MY) of guinea-pig antrum. In tissue, ICC-MY showed c-Kit positive reactions and produced driving potentials with the amplitude and frequency of about 62 mV and 2 times min(-1), respectively, in the presence of 1 microM nifedipine. Single ICC-MY isolated by enzyme treatment also showed c-Kit immunohistochemical reactivity. These cells were also identified by generation of spontaneous inward current under K(+) -rich pipette solution. The voltage clamp experiments revealed the amplitude of - 329 pA inward current at irregular frequency. With Cs(+)-rich pipette solution at V(h)=-80 mV, ICC-MY produced voltage-dependent inward currents (VDIC), and nifedipine (1 microM) blocked VDIC. Therefore, we successfully isolated c-Kit positive single ICC from guinea-pig stomach, and found that ICC-MY potently produced dihydropiridine sensitive L-type voltage-dependent Ca(2+) currents (VDCC(L)).

Prospective multicenter phase II clinical trial of FOLFIRI chemotherapy as a neoadjuvant treatment for colorectal cancer with multiple liver metastases

Purpose This study evaluated the efficacy of neoadjuvant chemotherapy combining 5-flurouracil/folinic acid with irinotecan (FOLFIRI) in colorectal multiple liver metastases regardless of resectability. Methods Forty-four patients with multiple (at least two) colorectal liver metastases were enrolled at seven tertiary referral hospitals between May 2007 and September 2010. All patients received the FOLFIRI chemotherapeutic regimen. Response to chemotherapy was assessed after three cycles (6 weeks) and once more after six cycles (12 weeks) of treatment. Results Objective response was noted in 27 patients (61.4%) and 4 patients (9.1%) had progressive disease. Of 44 patients, 10 patients (22.7%) underwent curative surgery (R0 resection) and 34 patients did not receive R0 resection. Grades 3 to 4 hematological toxicity was noted in 12 patients (27.3%) and grades 3 to 4 nonhematologic toxicity was identified in 5 patients (11.4%). Conclusion FOLFIRI chemotherapy as a neoadjuvant chemotherapy for multiple colorectal liver metastases regardless of resectability demonstrated the possibility of R0 resection, high rate of objective response, and tolerable toxicities in this study.

Mesh-Based Transperineal Repair of a Perineal Hernia After a Laparoscopic Abdominoperineal Resection

A perineal hernia (PH) is formed by a protrusion of intra-abdominal viscera through a defect in the pelvic floor. This is a rare complication after a conventional abdominoperineal resection (APR). However, the risk of a PH may be increased after a laparoscopic resection because this technique can cause fewer postoperative adhesions, predisposing the small bowel to sliding down toward the pelvis. However, only a few case reports describe the transperineal approach for the repair of a PH after a laparoscopic APR. We present a case of a PH after a laparoscopic APR; the PH was repaired with synthetic mesh by using a transperineal approach. A transperineal approach using a mesh to reconstruct the pelvic floor is less invasive and more effective. We suggest that this technique should probably be the first choice for treating an uncomplicated PH that occurs after a laparoscopic APR.

Impact of Hyperglycemia on Survival and Infection-Related Adverse Events in Patients with Metastatic Colorectal Cancer Who Were Receiving Palliative Chemotherapy

Purpose Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. Materials and Methods We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. Results The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). Conclusion Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.

Diagnostic and prognostic value of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography for colorectal cancer: comparison with conventional computed tomography

Background/Aims 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been used for preoperative staging of colorectal cancer (CRC). However, the diagnostic accuracy of FDG-PET/CT for detection of lymph node or distant metastasis and its prognostic role have not been well established. We therefore evaluated the diagnostic and prognostic value of FDG-PET/CT in comparison with conventional CT for CRC. Methods We investigated 220 patients who underwent preoperative FDG-PET/CT and CT, followed by curative surgery for CRC. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET/CT and CT for detection of lymph node metastasis and distant metastasis were evaluated. In addition, we assessed the findings of FDG-PET/CT and CT according to outcomes, including cancer recurrence and cancer-related death, for evaluation of prognostic value. Results For detection of lymph node metastasis, FDG-PET/CT had a sensitivity of 44%, a specificity of 84%, and an accuracy of 67%, compared with 59%, 65%, and 62%, respectively, for CT (P=0.029, P=0.000, and P=0.022). For distant metastasis, FDG-PET/CT had a sensitivity of 79%, a specificity of 94%, and an accuracy of 93%, compared with 79%, 87%, and 86%, respectively, for CT (P=1.000, P=0.004, and P=0.037). In addition, positive findings of lymph node metastasis and distant metastasis on FDG-PET/CT were associated significantly with cancer recurrence or cancer-related death (P=0.009, P=0.001, respectively). Conclusions Preoperative FDG-PET/CT had a higher specificity and accuracy compared to CT for detection of lymph node metastasis and distant metastasis of CRC. In addition, FDG-PET/CT could be a valuable prognostic tool for CRC.