Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
Antineoplastic Agents, Hormonal/adverse effects ; Disease Management ; Disease Progression ; Endometrial Hyperplasia/classification/etiology/*therapy ; Female ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Hysterectomy ; Molecular Targeted Therapy/methods ; Progesterone Congeners/therapeutic use ; Risk Factors ; Tamoxifen/adverse effects

BACKGROUND/AIMS: Studies evaluating the human pylorus as a sphincter are scanty and contradictory. Recently, we have shown technical feasibility of transposing the human pylorus for end-stage fecal incontinence. This unique cohort of patients provided us an opportunity to study the sphincter properties of the pylorus in its ectopic position. METHODS: Antro-pylorus transposition on end sigmoid colostomies (n = 3) and in the perineum (n = 15) was performed for various indications. Antro-pylorus was assessed functionally (digital examination, high resolution spatiotemporal manometry, barium retention studies and colonoscopy) and by imaging (doppler ultrasound, MRI and CT angiography) in its ectopic position. RESULTS: The median resting pressure of pylorus on colostomy was 30 mmHg (range 28-38). In benign group, median resting pressure in perineum was 12.5 mmHg (range 6-44) that increased to 21.5 mmHg (range 12-29) (P = 0.481) and 31 mmHg (range 16-77) (P = 0.034) on first and second follow-up, respectively. In malignant group, median post-operative pressures were 20 mmHg (range 14-36) and 21 mmHg (range 18-44) on first and second follow-up, respectively. A definite tone and gripping sensation were felt in all the patients on digital examination. On distal loopogram, performed through the diverting colostomies, barium was retained proximal to the neo-pyloric valve. Both perineal ultrasound and MRI showed viable transposed graft. CT angiography and color doppler studies confirmed vascular flow in the transposed position. CONCLUSIONS: The human pyloric valve can function as a tonic sphincter when removed from the gastroduodenal continuity.
Angiography ; Barium ; Cohort Studies ; Colon, Sigmoid ; Colostomy ; Fecal Incontinence ; Follow-Up Studies ; Gastroepiploic Artery ; Hand Strength ; Humans ; Manometry ; Perineum ; Pylorus ; Retention (Psychology) ; Sensation ; Transplants

PURPOSE: Perineal transposition of the antropyloric valve following an anorectal excision as a substitute for a permanent colostomy has recently been reported in humans. However, the problem of neural control still remains in these patients. Our aim herein was to study the anatomical feasibility of an anastomosis between the pudendal nerve branches (inferior rectal nerve) innervating the external anal sphincter and the anterior vagal branches of the perineally-transposed antropyloric segment in cadavers. METHODS: The antropyloric segment, along with its carefully dissected branch of the anterior vagus, was mobilized based on the left gastroepiploic pedicle in six fresh human cadavers. The antropyloric valve was then transposed in the perineum after the pudendal nerve branches had been dissected out, and an approximation of these two nerves was performed to ascertain the technical feasibility of their neural anastomosis. RESULTS: The anterior vagus innervating the antropylorus could be harvested in all cadavers below the hepatic division of the main vagus trunk. The inferior rectal nerve or its branches were found consistently around the 3 or the 9 o'clock position in the ischioanal fossa. An anatomical tension-free approximation of the anterior vagus branch (of the transposed antropyloric segment) to the inferior rectal nerve in the perineum was feasible in all the cadavers studied. CONCLUSION: An inferior rectal nerve anastomosis with the anterior vagal branch of the perineally-transposed antropyloric segment can be achieved anatomically. This preliminary step can be the basis for future animal studies and subsequent clinical application of the procedure for possible neural control of the transposed antropyloric segment in the perineum.
Anal Canal ; Animals ; Cadaver ; Colostomy ; Humans ; Perineum ; Pudendal Nerve ; Pylorus ; Vagus Nerve

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.
Aged ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Cell Proliferation ; Cisplatin/therapeutic use ; Cytoskeletal Proteins/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Stomach/drug effects/*pathology ; Stomach Neoplasms/diagnosis/drug therapy/*pathology ; Survival Analysis