Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

BACKGROUND: DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer. METHODS: Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS: We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma. CONCLUSIONS: Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.     

Treatment Guidelines for Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: When Can We Operate or Observe?

Background The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN. Methods We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea. Results Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor ≤2 cm without a mural nodule was 9.2%, for a tumor of ≤2 cm plus a mural nodule was 25%, and for other conditions such as tumor >2 cm, >25%. Conclusions Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of ≤2 cm without a mural nodule.     

Vesicovaginal fistula repair with genito-gluteal fold fat pad flap.

We report our experience of supratrigonal vesicovaginal fistula (VVF) repair cases developed after gynaecologic surgery. Two patients presented with urinary incontinence after hysterectomy and adjuvant radiation therapy for cervical carcinoma. Cystoscopy findings showed vesicovaginal fistula near the bladder neck area. In a transvaginal approach, we excised the fistulous tract and transferred the genito-gluteal fold fat pad flap for interpositioning. Postoperative cystography showed no evidence of leakage and no recurrence was found after a 1 year follow-up period. This flap technique is particularly useful for a vaginal cuff area fistula in terms of ease of dissection, lower donor site morbidity and large flap dimension. Also the fat pad provides neovascularity and lymphatic drainage, fills dead space, and enhances granulation tissue formation.     

Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs

BACKGROUND: Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation. RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.     

Surgical treatment of pseudosyndactyly of children with epidermolysis bullosa: a case report.

Recessive dystrophic epidermolysis bullosa (RDEB) is an uncommon and severe disorder characterised by trauma-induced blisters, intractable skin ulcers, scarring, milia, and nail dystrophy. We report the good result of both surgical release of fingers allowing spontaneous epithelisation without skin grafting and post-operative meticulous skin care without splinting, followed-up for one year.     

Efficacy of negative pressure therapy to enhance take of 1-stage allodermis and a split-thickness graft

Negative pressure therapy has been used in various conditions to promote wound healing. It has also been used to secure a skin graft by improving microcirculation and providing tight adhesion between the graft and the recipient bed. The authors coupled the idea of negative pressure therapy for 1-stage allodermis and a split-thickness skin graft. This prospective study presents 47 cases of skin defects treated by 1-stage allodermis and a split-thickness skin graft. The patients were divided into 2 groups either treated with simultaneous aid of negative pressure therapy for 5 days (group 1, n = 37) or a classic tieover dressing (group 2, n = 10). In group 1, 97.8% graft take was noted at day 5 and the mean time until complete healing was 5.8 days. In group 2, 84% graft take was noted at day 5 and mean time until complete healing was 8.9 days with an average number of 3.2 dressings. Statistically significant graft take (day 5) and time until complete healing was noted (P < 0.05). Good aesthetic and functional result mimicking a full-thickness skin graft was achieved in both groups. However, frequent dressings, longer time to heal, and more restriction to the graft site were needed for group 2. Split-thickness skin added to allodermis provided a sufficient amount of dermis to prevent contracture, and the negative pressure therapy ensured fast and complete take of the 2-layered composite graft. This option can be used to achieve healing mimicking a full-thickness skin graft without requiring large full-thickness donor sites.     

Endoscopic stenting for benign upper gastrointestinal strictures and leaks

Background

Self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) maybe used for the treatment of benign upper gastrointestinal (GI) leaks and strictures. This study reviewed our experience with stent insertions in patients with benign upper GI conditions.

Methods

Patients who underwent stent placement for benign upper GI strictures and leaks between March 2007 and April 2011 at a tertiary referral academic center were studied using an endoscopic database and electronic patient records. The technical success, complications, and clinical improvement after stent removal were compared according to type of stent. The outcomes measured were clinical response, adverse events, and predictors of stent migration.

Results

Thirty-eight patients (50 % male, mean age = 54 years, range = 12–82) underwent 121 endoscopic procedures. Twenty patients had stents placed for strictures, and 18 had stents placed for leaks. Stent placement was technically successful in all patients. The average duration of stent placement was 54 days (range = 18–118). Clinical improvement immediately after stent placement was seen in 29 of the 38 patients (76.3 %). Immediate post-procedure adverse events occurred in 8 patients. Late adverse events were seen in 18 patients. Evidence of stent migration occurred in 16 patients and was seen in 42 of the 118 successfully placed stents (35.5 %). Migration was more frequent with fully covered SEMS (p = 0.002). After stent removal, 27 patients were evaluable for long-term success (median follow-up time of 283 days, IQR 38–762). Resolution of strictures or leaks was seen in 11 patients (40.7 %). Predictors for long-term success included increasing age and if the stent did not cross the GE junction.

Conclusions

Placement of SEPS and SEMS for benign refractory strictures and fistulas has modest long-term clinical efficacy and is limited by a significant migration rate. Stent migration is common and frequent with fully covered SEMS compared to other types of stents, regardless of indication or location.     

Clinical importance of the updated Oxford classification in allograft IgA nephropathy

With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST‐C scores of the patients. The main study outcome was death‐censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using the Cox regression analysis. Three hundred thirty‐three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end‐stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST‐C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST‐C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD.     

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

Objective

To investigate whether the quantitative elasticity index of shear wave elastography (SWE) can predict extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) preoperatively.

Methods

A total of 208 patients with pathology confirmed PTC whom underwent SWE during preoperative staging US between April 2011 to June 2012 were included.SWE indices of E _mean, E _max, E _min of the index malignancy, the ratios between E _mean of the lesion and parenchyma (E _ratio-P), and muscle (E _ratio-M), and grayscale US findings, including ETE, multifocality, bilaterality, and central and lateral lymph node (LN) metastasis were evaluated. The correlations of SWE indices and grayscale US findings with pathologic prognostic factors of PTC were analyzed by Chi square or Fisher’s exact test, and multivariate regression analysis.

Results

ETE was associated with E _mean, E _max, E _min, and E _ratio-M (P = 0.005, 0.009, 0.016 and <0.001, respectively), multifocality was associated with E _mean, E _max, and E _min (P = 0.028, 0.007, and 0.004, respectively), and central LN metastasis was associated with E _ratio-M (P = 0.03). On multivariate analysis, E _mean and E _min were independent factors for predicting ETE (P = 0.032, 0.049, respectively).

Conclusions

Quantitative elasticity index of SWE could predict pathologic ETE, and SWE could be a complimentary method to grayscale US for preoperative prediction of prognostic factors of PTC.     

Ionic currents in single smooth muscle cells of the human vas deferens

PURPOSE: Smooth muscle cells of the vas deferens have an important role in carrying sperms to the exterior but little is known of their electrophysiological properties. We characterized the voltage-gated ion channel currents in single smooth muscle cells of the human vas deferens (HVSMCs). MATERIALS AND METHODS: We observed contractile responses of 8 circular smooth muscle strips of the human vas deferens to a high concentration (10 mM) of tetraethylammonium. HVSMCs were isolated using proteolytic enzymes (collagenase and papain), and were used for an electro-physiological study using whole cell and inside-out patch clamp configurations. RESULTS: The application of 10 mM tetraethylammonium induced rhythmic contractions of the strips. When HVSMCs were dialyzed with a KCl solution, step depolarizations of membrane potential evoked oscillatory outward K currents that were not inactivated. The large conductance Ca activated K (BKCa) and delayed rectifier components of the outward current were identified. The BKCa channel showed a large single channel conductance (162.7 +/- 13.2 pS with 5 mM K in the patch pipette). Two types of Ca currents were identified in the whole cell configuration. With a cell held at -50 mV an L-type Ca current was present during a depolarizing step pulse. From a holding potential of -90mV L-type and T-type Ca currents were elicited by depolarizing step pulses. CONCLUSIONS: HVSMCs have 2 (L and T) types of Ca channels and 2 types of K (BKCa and delayed rectifier) channels. Voltage dependent changes of these ion channels and their interactions may be important in regulating vas contractility.