Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function.

OBJECTIVE: To investigate the functional interaction between the Wnt/ß-catenin and protein kinase B (Akt) pathways in leiomyoma stem cells (LSC). DESIGN: Laboratory study. SETTING: Research laboratory. PATIENT(S): Premenopausal women (n = 36; age range: 28 to 49 years) undergoing hysterectomy or myomectomy for leiomyoma. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression, protein phosphorylation, and cell proliferation. RESULT(S): Cells from human leiomyoma tissues were sorted by fluorescence-activated cell sorting (FACS) into three populations: LSC, intermediate cells (LIC), and differentiated cells (LDC) with the function of the Wnt/ß-catenin and Akt signaling pathways in leiomyoma cells evaluated using real-time quantitative polymerase chain reaction and immunoblot analyses. The Wnt/ß-catenin signaling pathway components were differentially expressed in each leiomyoma cell population. WNT4 was distinctly overexpressed in LIC, and its receptor FZD6 was primarily expressed in LSC. WNT4 stimulated Akt phosphorylation, activated ß-catenin, and increased primary leiomyoma cell proliferation. These stimulatory effects were abolished by cotreatment with the Akt inhibitor, MK-2206. WNT4 up-regulated the expression of pro-proliferative genes, c-Myc and cyclin D1, specifically in LSC; this was also abrogated by Akt inhibition. CONCLUSION(S): Our data suggest that WNT4 regulates LSC proliferation via Akt-dependent ß-catenin activation, representing a key step toward a better understanding of LSC regulation and potentially novel therapeutic targets.

Suspension of ulipristal acetate for uterine fibroids during ongoing EMA's review of liver injury risk: Unfortunate timing during the Covid-19 pandemic!

OBJECTIVE: EMA decided that with ulipristal acetate (UPA) treatment for uterine fibroids, should be discontinued due to the associated risk of hepatic failure, We analyzed whether the risk of recurrent symptoms due to fibroids may lead to an increased risk of Covid -19 infection and death, that would exceed the former risk of hepatic failure and transplantation. STUDY DESIGN, SIZE, DURATION: We used a Markov model to generate probabilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: There are currently about 36,250 treated patients in Europe. We estimated bleeding probabilities, while using or discontinuing UPA, which may induce a need of medical or surgical management in symptomatic patients, and increase the risk of acquiring a Covid-19 infection, and die from it. We also estimated the risk of suffering a hepatic failure and hepatic transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Based on our assumptions, ceasing UPA during a Covid 19 pandemic may be associated with a fatality ratio between 4 and 18, due to the Pandemic, whereas pursuing UPA would be associated with a fatality rate due to the pandemic between 1-2, and an added fatality rate due to hepatic impairment of 1. The added risk of stopping UPA may range between 2 and 15 additional deaths. Our calculations suggest that the decision to stop UPA in the middle of the Covid- 19 pandemic may be untimely, since it may result in an increased risk of Covid-19 infection, due to the recurrence of symptoms and the need for medical and surgical treatment. WIDER IMPLICATIONS OF THE FINDINGS: A decision, like the one EMA took need to be taken in a wider health context of a population, than simply analyzing its role as regulating agent for medications.

STMN1 and MKI67 Are Upregulated in Uterine Leiomyosarcoma and Are Potential Biomarkers for its Diagnosis.

BACKGROUND The aim of this study was to investigate STMN1 and MKI67 expression in uterine leiomyosarcoma and their potential roles as biomarkers for diagnosis. MATERIAL AND METHODS The expression of STMN1 and MKI67 mRNA in uterine leiomyosarcoma were investigated in TCGA database. The overall survival (OS) and disease-free survival (DFS) were compared between high and low expression groups. Seventy-two patients who received hysterectomy were included and divided into 4 groups: uterine normal smooth muscle tissue (UNSM=30), uterine leiomyoma (UL=30), uterine cellular leiomyoma (UCL=24), and uterine leiomyosarcoma (ULS=18). The STMN1 and MKI67 protein expression of the 4 groups were examined by immunohistochemistry (IHC) assay. RESULTS The expression level of STMN1 mRNA in cancer tissue was significantly higher than those of normal uterine smooth muscle tissue. The high and low expression of STMN1 and mki67 gene mRNA was not related to the patients' OS and DFS (P>0.05). The positive rate of STMN1 protein in uterine leiomyosarcoma was 100.00%, which was significantly higher than that of the other 3 groups (χ²=11.72, P=0.008). And the positive rate of KIM67 protein in uterine leiomyosarcoma was 77.78%, which was also significantly higher than that of the other 3 groups (χ²=48.89, P=0.000). The diagnostic sensitivity and specificity were 77.78%, 90.74% for STMN1 combined MKI67 with the positive predictive value and negative predictive value of 73.68% and 92.45%, respectively. CONCLUSIONS STMN1 and MKI67 were upregulated in uterine leiomyosarcoma and act as potential biomarkers for uterine leiomyosarcoma diagnosis.

Smooth Muscle Tumors of the Visceral Adnexal and Uterine Ligaments and Adnexal Connective Tissue: A Clinicopathologic Study of 67 Cases.

The endopelvic fascia is a biomechanical network of supportive tissue that suspends and secures the female reproductive organs to the pelvic sidewall. Several visceral adnexal and uterine ligaments are part of this framework, and we have observed that smooth muscle tumors (SMTs) arising from these structures morphologically resemble gynecologic smooth muscle neoplasms. To determine whether gynecologic smooth muscle tumor criteria for malignancy are valid in these tumors, we evaluated the morphologic features of 67 tumors from 67 patients and correlated our findings with patient outcome. Using current uterine SMT WHO definitions, 57 tumors (85%) were classified as leiomyoma, 2 (3%) as smooth muscle tumor of uncertain malignant potential (STUMP), and 8 (12%) as leiomyosarcoma. Clinical follow-up was available for 88% of patients (range: 1-296 mo, mean: 174 mo, median: 79 mo). Only 1 case of leiomyosarcoma had metastasis at time of presentation, but 6 of 8 (75%) patients eventually died of disease. The other 2 cases of leiomyosarcoma that have not recurred are 11 and 16 mo from initial diagnosis. No cases of STUMP or leiomyoma recurred. On the basis of morphologic features and patient outcome, we believe these tumors distribute into similar categories of leiomyoma, STUMP and leiomyosarcoma, paralleling the biologic potential of uterine SMTs as well as SMTs of other gynecologic sites. We propose use of uterine WHO SMT criteria to classify spindled SMTs that arise in the visceral adnexal and uterine ligaments and adnexal connective tissue.

The selected biomarker analysis in 5 types of uterine smooth muscle tumors.

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Fumarase-deficient Uterine Leiomyomas: An Immunohistochemical, Molecular Genetic, and Clinicopathologic Study of 86 Cases.

Loss-of-function germline mutations in the fumarase (FH) gene of the Krebs cycle characterize hereditary leiomyomatosis and renal cell cancer syndrome. Fumarase (FH) deficiency can be diagnosed by the loss of immunohistochemical expression. In this study, we investigated the occurrence and clinicopathologic features of FH-deficient uterine smooth muscle tumors (SMTs). A total of 1583 uterine and 157 nonuterine SMTs were examined using a polyclonal FH antibody and automated immunohistochemistry, and 86 uterine leiomyomas with an FH loss were identified. The frequencies of FH deficiency for subcohorts of uterine SMTs were 1.6% for unselected nonatypical leiomyomas, 1.8% for cellular leiomyomas, 37.3% for atypical leiomyomas, and 0% for leiomyosarcomas. One extrauterine, retroperitoneal estrogen receptor-positive leiomyoma was also FH deficient. The patient age of FH-deficient uterine leiomyomas was 20 to 52 years (median, 38 y). Grossly, these tumors were often soft and amorphous resembling a fibrothecoma. Histologically, the FH-deficient nonatypical leiomyomas lacked cellular packeting and distinct collagenous zones and showed chain-like or palisading nuclear arrangements, prominent staghorn-shaped blood vessels, oval nuclei with no or at most mild atypia, small eosinophilic nucleoli, and a low mitotic rate (0 to 1/10 HPF). The FH-deficient atypical leiomyomas had nuclear atypia often manifesting as multinucleation, prominent eosinophilic nucleoli, and mitotic activity up to 7/10 HPF, with atypical mitoses seen in 32% of cases. However, similar histologic changes were seen in some non-FH-deficient atypical leiomyomas. Loss-of-function FH-gene mutations including 5 whole-gene deletions and 3 frameshift mutations were identified in 8 of 16 FH-deficient nonatypical leiomyomas using multiplex ligation-dependent probe amplification and Sanger sequencing, respectively. Follow-up data on patients with FH-deficient atypical uterine leiomyomas revealed 19 patients alive (median follow-up 27 y) and 5 patients dead. Deaths occurred 9 to 30 years after surgery at a median age of 72 years; causes of death could not be determined. These results indicate that FH-deficient uterine leiomyomas occur with a high frequency among atypical leiomyomas and infrequently in nonatypical leiomyomas and are often histologically distinctive. They seem to have a low biological potential and lack any significant association with leiomyosarcoma.

May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?

Several studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHH target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLI1, GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1, and GLI3 was detected in these samples. Strong expression of SHH was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs.

Comparison of Survival Outcomes in Women with Unsuspected Uterine Malignancy Diagnosed After Laparotomic Versus Laparoscopic Myomectomy: A National, Population-Based Study.

PURPOSE: The primary objective of our study was to investigate the effect of morcellation on overall survival in women with unsuspected uterine malignancy (UUM) diagnosed after myomectomy by comparing women who underwent laparotomic myomectomy to those who underwent laparoscopic myomectomy. The secondary objective was to estimate the incidence of UUM diagnosed after myomectomy. METHODS: We analyzed the mortality and incidence of women with UUM diagnosed after myomectomy using data from the national health insurance database between 2009 and 2013. To extract women with or without UUM diagnosed after myomectomy, we used diagnosis (C54.X) and procedure codes. We used the indicator of suspicion of death to verify deaths. RESULTS: During the study period, among the study population of approximately 23 million women per year, 102144 women underwent myomectomy. Of them, 69955 and 32085 women were enrolled onto the laparotomic and laparoscopic groups, respectively. In each group, the numbers of women with UUM diagnosed after myomectomy were 76 and 50, respectively. The incidences of UUM and UUM excluding endometrial cancer, respectively, were 0.1, 0.15 % (p = 0.046) and 0.05, 0.07 % (p = 0.147) in each group, respectively. The overall 3-year survival rates for patients with UUM and UUM excluding endometrial cancer were 97.6 ± 0.2 % (n = 23), 91.5 ± 0.5 % (n = 12); and 93.8 ± 0.6 % (n = 8), 93.8 ± 0.6 % (n = 5) in each group, respectively. Additionally, there were no statistically significant differences between the groups with respect to overall survival of women with UUM with or without endometrial cancer (log-rank test; p = 0.14) (time-dependent Cox regression model; p = 0.93). CONCLUSIONS: There was no difference in the overall survival of women with UUM with or without endometrial cancer between groups. The incidence of UUM with or without endometrial cancer diagnosed after myomectomy was quite low.

Economic and Survival Implications of Use of Electric Power Morcellation for Hysterectomy for Presumed Benign Gynecologic Disease.

BACKGROUND: Electric power morcellation during laparoscopic hysterectomy allows some women to undergo minimally invasive surgery but may disrupt underlying occult malignancies and increase the risk of tumor dissemination. METHODS: We developed a state transition Markov cohort simulation model of the risks and benefits of hysterectomy (abdominal, laparoscopic, and laparoscopic with electric power morcellation) for women with presumed benign gynecologic disease. The model considered perioperative morbidity, mortality, risk of cancer and dissemination, and outcomes in women with an underlying malignancy. We explored the effectiveness from a societal perspective stratified by age (<40, 40-49, 50-59, and ≥60 years). RESULTS: Under all scenarios, modeled laparoscopic hysterectomy without morcellation was the most beneficial strategy. Laparoscopic hysterectomy with morcellation was associated with 80.83 more intraoperative complications, 199.64 fewer perioperative complications, and 241.80 fewer readmissions than abdominal hysterectomy per 10 000 women. Per 10 000 women younger than age 40 years, laparoscopic hysterectomy with morcellation was associated with 1.57 more cases of disseminated cancer and 0.97 fewer deaths than abdominal hysterectomy. The excess cases of disseminated cancer per 10 000 women with morcellation compared with abdominal hysterectomy increased with age to 47.54 per 10 000 in women age 60 years and older. Compared with abdominal hysterectomy, this resulted in 0.30 (age 40-49 years), 5.07 (age 50-59 years), and 18.14 (age 60 years and older) excess deaths per 10 000 women in the respective age groups. CONCLUSION: Laparoscopic hysterectomy without morcellation is the most beneficial approach of the three methods of hysterectomy studied. In older women, the risks of electric power morcellation may outweigh the benefits of minimally invasive hysterectomy.

Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma.

The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors.

Morcellation of occult uterine malignancies: an Australian single institution retrospective study.

INTRODUCTION: Morcellation for tissue extraction during laparoscopic hysterectomy or myomectomy has recently been questioned because of the potential to spread occult uterine cancers. The Australian Therapeutic Goods Administration (TGA) issued a safety advisory in August 2014, estimating the risk of occult malignancy in the Australian population to be one in 1000 or lower, based on estimates from overseas studies in the absence of any local data. AIMS: The aim of this study was to determine the incidence of occult uterine malignancies in morcellated surgical specimens at St John of God Hospital in Perth, Western Australia. MATERIALS AND METHODS: All women who had a hysterectomy or myomectomy with morcellation of the surgical specimen for presumed benign uterine fibroids at our institution from 01 November 2009 to 12 March 2015 were identified and stratified into benign disease, uncertain malignant potential and malignant. RESULTS: Seven hundred and thirty-four women were included, and three malignancies were identified: two cases with leiomyosarcoma (LMS) and another with an endometrioid endometrial adenocarcinoma (EAC). One case of serous tubal in situ carcinoma (STIC) and two cases of benign metastasising leiomyoma/leiomyomatosis were also identified. The overall risk of malignancy in a morcellated surgical specimen was 0.41% (three in 734). The risk of morcellating an incidental uterine malignancy was 0.27% for LMS and 0.14% for EAC. All three incidental malignancies were diagnosed in premenopausal women. CONCLUSIONS: The risk of unintended morcellation of uterine malignancy in our study is higher than that estimated by the Australian TGA and highlights the urgent need for further studies in Australia.

Incidence of additional treatments in women treated with MR-guided focused US for symptomatic uterine fibroids: review of 138 patients with an average follow-up of 2.8 years.

PURPOSE: To assess long-term outcomes of magnetic resonance (MR)-guided focused ultrasound (US) treatments of uterine fibroids. MATERIALS AND METHODS: A retrospective follow-up of 138 patients treated at a single institution between March 2005 and November 2011 was conducted. The patients were not part of a clinical study and were followed through retrospective review of their medical records and telephone interviews to assess additional treatments for fibroid-related symptoms. Survival methods, including Cox proportional hazards models, were used to assess the association between incidence of additional treatments and patient data obtained during screening before treatment. RESULTS: The average length of follow-up was 2.8 years (range, 1-7.2 y). The cumulative incidence of additional treatments at 36 months and 48 months after MR-guided focused US was 19% and 23%, respectively. Women who did not need additional treatment were older than women who did (46.3 y ± 5.6 vs 43.0 y ± 5.8; P = .006; hazard ratio, 0.855; 95% confidence interval, 0.789-0.925). Additionally, women with heterogeneous or bright fibroids on T2-weighted MR imaging were more likely to require additional treatment compared with women with homogeneously dark fibroids (hazard ratio, 5.185 or 5.937, respectively; 95% confidence interval, 1.845-14.569 or 1.401-25.166, respectively). Physician predictions of treatment success, recorded during the screening process, had significant predictive value (P = .018). CONCLUSIONS: The long-term rates of additional interventions after MR-guided focused US of symptomatic uterine fibroids were found to be comparable with other uterine-sparing procedures, such as uterine artery embolization or myomectomy. Older patient age and homogeneously dark fibroids were associated with fewer additional treatments. Physician assessment of treatment success was found to be a valuable tool in patient screening.

Endoscopic submucosal dissection in the treatment of gastric submucosal tumors: results from a retrospective cohort study.

BACKGROUND: A submucosal tumor (SMT) of the stomach, which is an occasional finding during routine upper gastrointestinal endoscopy, may pose diagnostic and therapeutic challenges. METHODS: To assess whether endoscopic submucosal dissection (ESD) is a feasible approach to definitively cure SMTs, the authors performed a retrospective cohort study with two endoscopic italian centers. RESULTS: The study consisted of 20 patients with SMTs who underwent ESD. The patients underwent ESD and were followed up by endoscopy. We analyzed complete resection rate, frequency of complications, and survival. The overall rate of R0 resection was 90 % (18/20), with two endoscopic failures, one for a submucosal tumor and one for a neoplasm deeply infiltrating the proper muscle layer. The median procedure time was 119.1 min (range 40-240 min). The median size of the resected specimens was 29 mm (range 15-60 mm). Perforation occurred in 3 patients; all were treated conservatively. There were no cases of severe bleeding. Based on histopathological findings, 6 cases of ectopic pancreas, 1 of ectopic spleen, 3 of leiomyoma, and 10 of gastrointestinal stromal tumor (GIST) were diagnosed. Complete resection was obtained in all GIST cases. Among the 10 GIST cases treated by ESD, no death occurred: the 5-year disease-specific survival rate was 100 %. CONCLUSIONS: The high success rate of 90 % and the low incidence of complications should indicate ESD is the correct diagnostic and definitive treatment in selected patients.

Smooth muscle neoplasms of the urinary bladder: a clinicopathologic study of 51 cases.

Smooth muscle neoplasms of the urinary bladder are relatively rare. We report the largest series to date examining the clinicopathologic features of leiomyomas and leiomyosarcomas of the bladder. This study sought to clarify several issues relating to smooth muscle neoplasms of the urinary bladder: (1) How to distinguish leiomyomas of the bladder from normal muscularis propria on transurethral resection (TUR) specimens; (2) Whether symplastic leiomyomas can be diagnosed in the bladder; (3) Can leiomyoma be definitively diagnosed on biopsy or TUR without the risk of there being unsampled leiomyosarcoma; and (4) Is the grade of leiomyosarcoma seen on biopsy or TUR heterogeneous and hence possibly not representative of the true grade. Thirty-one leiomyomas and 20 leiomyosarcoma cases of urinary bladder from 3 tertiary care medical centers were examined. Leiomyosarcoma cases were subdivided into low-grade and high-grade based on mitotic count (> or =5/10 HPF) and nuclear atypia. The mean age of the patients with leiomyoma and leiomyosarcoma was 52 and 58, respectively. The M:F ratio was significantly higher in patients with leiomyosarcoma (2:1) compared with leiomyoma (1:3), p<0.005. The specimen consisted of 20 TUR and 11 transurethral biopsies (TUBx) for leiomyomas, and 10 TUR, 3 TUBx, 5 cystectomies (Cyst), and 2 partial cystectomies (pCyst) for leiomyosarcomas. LEIOMYOMAS: Notable features in leiomyomas were hyalinization (7/31), degenerative atypia (7/31), necrosis (4/31), myxoid changes (2/31), and focal fatty metaplasia (1/31); although no surface ulceration was identified. Clinical follow-up was available for 24 patients (12 to 108 mo; mean 36 mo); 4 lost to follow-up and 3 recent cases. Two patients had repeat TUR within a year of the initial diagnosis with the same bland leiomyoma on histology, probably reflecting persistence of earlier unresected tumor as opposed to recurrent tumor. None of the patients were diagnosed with leiomyosarcoma on follow-up, including 7 cases with degenerative atypia. LEIOMYOSARCOMA: Of the 20 leiomyosarcomas, 8 were classified as low-grade and 12 as high-grade sarcomas. Histologic features included epithelioid morphology (5/20; 1 entirely epithelioid), tumor cell necrosis (11/20), and mucosal ulceration (7/20). Infiltration into the muscularis propria was seen predominantly as a nodular growth pattern with some cases exhibiting an irregular infiltrative pattern (6/10 with evaluable borders); an infiltrative pattern was not restricted to high-grade lesions. Lesional heterogeneity was present in only 1 case on the same specimen, which showed both low-grade and high-grade areas. Another case was low grade on TUR, yet high grade at cystectomy. None of the cases of leiomyosarcomas had areas histologically resembling leiomyoma. Clinical follow-up was available for 15 patients with leiomyosarcoma (11 to 144 mo; mean 47 mo); 3 lost to follow-up and 2 recent cases. Only 1 patient with low-grade sarcoma experienced 2 local recurrences treated only by TUR and is currently free of disease. Disease-related mortality was significantly higher in patients with high-grade compared with low-grade leiomyosarcomas (50% vs. none, respectively; P<0.001). Leiomyoma (including symplastic leiomyoma) may be diagnosed on TUR without risk of underdiagnosing unsampled leiomyosarcoma. High-grade leiomyosarcomas are highly aggressive neoplasms compared with low-grade leiomyosarcomas; in most cases grade can be accurately determined on TUR.

Venous thromboembolism as a complication of uterine fibroids: a retrospective descriptive study.

This study describes cases of fibroids with venous thromboembolism (VTE) managed at UHWI between the years 1999-2004. We examined records to find patients with fibroids and VTE diagnosed before or after surgery. We found 438 women with VTE and 72 of these (16.4%) with fibroids. A total of 1,979 patients had fibroids during the period; cases were therefore 3.63% of fibroids. Cases were younger, median age 44 years than the total cohort: the median age was 57 and the mean age was 55.43 (SD 19.87) p = 0.000 about 9.5 years older than cases. Age over 50 years was less common in cases 27% vs 52% p = 0.0001 as were other risk factors for VTE such as cancer 4.9 vs 14% p = 0.03; diabetes 8.6 vs 25.2% p = 0.004 and cardiac disease 8.6% vs 26.6% p = 0.002 . However, thrombocytosis was more frequent, 23% vs 9% p = 0.008. Other risk factors were not significantly different. A total of 21 cases (29.1%) had surgery for fibroids; 15 (71.4%) hysterectomy, and six (28.5%) myomectomy. Most cases 67/72 (93%) had VTE without surgery. Of the five cases with VTE after surgery for fibroids, none had prophylactic heparin. Of the cases, 15 died--23% of women with VTE at PM and 0.8% of those with fibroids.

A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors.

Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging. Using a series of tissue microarrays that contain 245 cases of leiomyosarcomas (102 gynecologic) with survival data, and 49 cases of uterine leiomyoma, we examined the ability of selected immune-markers (estrogen receptor (ER) and WT1) to distinguish between leiomyosarcomas of gynecologic and nongynecologic origin. In addition, we examined whether immunostains for p16, p53 and Ki-67 could distinguish between malignant and benign gynecologic smooth muscle tumors. ER nuclear positivity was observed in 3 and 50% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). Nuclear WT1 positivity was seen in 0 and 8% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). 87% of primary gynecologic leiomyosarcomas and 2% of uterine leiomyomas showed diffuse (>or=50% of cells) p16 staining (P<0.001). 23% of gynecologic leiomyosarcomas showed p53 immunopositivity (>or=50% of cells) whereas none of the leiomyomas were positive for p53 (P<0.001). 65% of the gynecologic leiomyosarcomas and 0% of the leiomyomas exhibited >10% Ki-67 proliferation index (P<0.001). Diffuse p16 and p53 immunopositivity and high Ki-67 proliferation index, singly or in combination, yielded an overall sensitivity of 92% and specificity of 98% for distinguishing between gynecologic leiomyosarcomas and leiomyomas and can be used as indicators of malignancy for gynecologic smooth muscle tumors. Although ER positivity can be used to support the gynecologic origin of a leiomyosarcomas, nuclear WT1 immunostaining is of little use.

Cervical leiomyoma in an aged goat leading to massive hemorrhage and death.

An adult female Toggenburg goat with a history of acute vaginal bleeding and death was presented for postmortem examination. Necropsy, histologic examination, and immunohistochemical staining revealed the presence of a leiomyoma that originated from the uterine cervix, occupied most of the vaginal lumen, and had a bleeding, frayed artery in the caudal end.

Supracricoid laryngectomy with cricohyoidoepiglotto-pexy or cricohyoido-pexy: experience on 32 patients.

OBJECTIVE: Supracricoid laryngectomy (SCL) with Cricohyoidoepiglotto-pexy (CHEP) or Cricohyoido-pexy (CHP) is an organ preservation surgery indicated for early and selected advanced laryngeal cancers. To verify the clinical usefulness of supracricoid laryngectomy versus total laryngectomy, a retrospective review was conducted. METHODS: We summarized the clinical and postoperative data of 32 patients who received SCL over the past 9 years (1997-2005). Five-year survival rate of the SCL patient group (29 cases) was compared with that of the patient group receiving total laryngectomy (35 cases) within the same period. RESULTS: Wound infection was detected in 12 patients (38%). Those with severe infection, which required surgical intervention, included two cases of ruptured pexis and two cases showing cricoid cartilage necrosis induced by Forestier disease. There were two T4 cases that resulted in extensive excision. In one case, excision involved the posterior part of the cricoid cartilage resulting in insufficient closure of the neoglottis; the patient received total laryngectomy 30 months after SCL-CHEP because of persistent aspiration of liquid diet. In the other T4 case, the tumor invaded the thyroid and arytenoid cartilages but not the cricoid cartilage. Reposition of the remaining corniculate cartilage resulted in sufficient closure of the neoglottis; this patient subsequently acquired satisfactory laryngeal function. The 5-year overall survival rate was 86% for SCL group and 61% for the total laryngectomy group (limited to Stages III and IV glottic cancers). The causes of the four deaths were distant metastasis, neck metastasis, and intercurrent disease, respectively. Two patients are alive with distant disease. CONCLUSION: Through our experience in this series, the functional and oncological results of SCL showed certain advantages over those of total laryngectomy. Particularly, the clinical impact of SCL-CHEP was impressive; this technique needs is recommended to both head and neck surgeons and patients.