Recurrent pelvic organ prolapse after hysterectomy; a 10-year national follow-up study.

PURPOSE: Hysterectomy may be a risk factor for pelvic organ prolapse (POP). We assessed the risk of recurrent POP (operations and visits) after hysterectomy among women with previous POP. We also studied patient and operation related risk factors for POP recurrence. METHODS: This retrospective cohort study included 1697 women having previous POP diagnosis or POP at the time of hysterectomy (FINHYST 2006 cohort). Follow-up was until the end of 2016. The data was derived from the Finnish National Care register linked to the cohort. Hysterectomy approaches and other demographics were compared to the risk of a prolapse diagnosis and/or surgery. Cox regression model was used to identify hazard ratios. RESULTS: Following hysterectomy, a total of 280 women (16.5%) had a POP reoperation and 359 (21.2%) had an outpatient visit due to POP. Vaginal vault prolapse repair was the most common POP reoperation (n = 181, 10.7%), followed by anterior wall repair (n = 120, 7.1%). Median time to POP reoperation was 3.7 years. Hysterectomy approach did not affect reoperations or visits. Previous cesarean section and anterior repair during hysterectomy were associated with decreased risk, whereas concomitant sacrospinous fixation and uterus prolapse as the main indication led to increased risk of anterior/vault prolapse reoperations. Concomitant posterior repair decreased posterior reoperations and visits, but uterus weight over 500 g caused a fivefold increased risk of posterior prolapse visit. Residential status was associated with elevated risk of any POP reoperations and visits. CONCLUSIONS: Approximately one out of five women suffering from POP ensue POP reoperation or visit after hysterectomy. These high rates are independent on hysterectomy approach, but probably indicate that hysterectomy may worsen previous pelvic floor dysfunction.

Pelvic organ prolapse after hysterectomy: A 10-year national follow-up study.

INTRODUCTION: Hysterectomy may have an effect on the pelvic floor. Here, we evaluated the rates and risks for pelvic organ prolapse (POP) surgeries and visits among women with a history of hysterectomy for benign indication excluding POP. MATERIAL AND METHODS: In this retrospective cohort study 3582 women who underwent hysterectomy in 2006 were followed until the end of 2016. The cohort was linked to the Finnish Care Register to catch any prolapse-related diagnoses and operation codes following the hysterectomy. Different hysterectomy approaches were compared according to the risk for a prolapse, including abdominal, laparoscopic, laparoscopic-assisted vaginal and vaginal. The main outcomes were POP surgery and outpatient visit for POP, and Cox regression was used to identify risk factors (hazard ratios [HR]). RESULTS: During the follow-up, 58 women (1.6%) underwent a POP operation, of which a posterior repair was the most common (n = 39, 1.1%). Outpatient visits for POP symptoms occurred in 92 (2.6%) women of which posterior wall prolapses (n = 58, 1.6%) were the most common. History of laparoscopic-assisted vaginal hysterectomy were associated with risk for POP operation (HR 3.0, p = 0.02), vaginal vault prolapse operation (HR 4.3, p = 0.01) and POP visits (HR 2.2, p < 0.01) as compared to the approach of abdominal hysterectomy. History of vaginal deliveries and concomitant stress urinary continence operation were associated with the risk for a POP operation (HR 4.4 and 11.9) and POP visits (HR 3.9 and 7.2). CONCLUSIONS: Risk for POP operations and outpatient visits for POP symptoms in hysterectomized women without a preceding POP seems to be small at least 10 years after hysterectomy. History of LAVH, vaginal deliveries and concomitant stress urinary incontinence operations increased the risk for POP operations after hysterectomy. These data can be utilized in counseling women considering hysterectomy for benign indication.

Decreasing trend and changing indications of hysterectomy in Finland.

INTRODUCTION: Hysterectomy has been one of the most common surgical procedures in women in Finland. We studied the population-based trends of hysterectomy and its indications from 1986 to 2017. MATERIAL AND METHODS: A retrospective population-based cohort was created from the Care Register for Health Care by identifying women who had a hysterectomy from 1986 to 2017 and calculating the number of women from the Digital and Population Data Services Agency. We estimated the number and incidence of hysterectomy by period and age as well as by indication. We considered the primary diagnosis at the time of surgery as the indication of hysterectomy. RESULTS: The number of hysterectomies increased from 7492 procedures in 1986 to 12 404 procedures in 1998, and reduced substantially after that to 5971 procedures in 2017, the turning point being in 1999. The incidence rate of hysterectomy has decreased on average by 2.5% annually from 432.6 per 100 000 women in 1998-2001 to 224.5 per 100 000 women in 2014-2017. The median age at the time of hysterectomy has increased from 51 years in 1998-2001 to 55 years in 2014-2017. The cumulative burden of hysterectomy by age of 60 years has nearly halved from the first 4-year period (23%) to the last (12%). After 2010, the most common indication has been genital prolapse and incontinence, whereas earlier it was uterine fibroids. CONCLUSIONS: The number and incidence of hysterectomies have fluctuated during the observation period 1986-2017 and decreased considerably during the past 17 years in Finland. This is probably a result of the availability of hormonal and other conservative treatment options for bleeding disorders and uterine fibroids. As hysterectomy practically removes the risk for endometrial cancer, the change in hysterectomy incidence over time emphasizes the importance of correcting endometrial cancer incidence according to hysterectomy incidence.

Cesarean scar defect: a prospective study on risk factors.

BACKGROUND: Cesarean scar defect (isthmocele) is a known complication after cesarean delivery. It has become more common due to a rising cesarean delivery rate. Isthmocele has been associated with various gynecological and obstetric problems such as uterine rupture, cesarean scar pregnancy, and bleeding disorders. OBJECTIVE: We sought to prospectively investigate factors associated with the risk for isthmocele assessed by sonohysterography. STUDY DESIGN: A prospective observational cohort study was conducted in 401 nonpregnant women who were recruited within 3 days of cesarean delivery. Women were evaluated with sonohysterography 6 months after cesarean delivery to detect a possible isthmocele. The ultrasonographer was blinded to any clinical information. The main outcome measure was the presence of isthmocele. Type of surgery (elective vs emergency), maternal background variables, and factors related to pregnancy, labor, and postoperative recovery were analyzed in relation to isthmocele. A logistic regression model was used to assess independent risk factors from univariate analysis. RESULTS: In all, 371 women were examined with sonohysterography resulting in a follow-up rate of 92.5%. The prevalence of isthmocele was 45.6%. Independent risk factors for isthmocele development were a history of gestational diabetes (odds ratio, 1.73; 95% confidence interval, 1.02-2.92; P = .042), previous cesarean delivery (odds ratio, 3.14; 95% confidence interval, 1.90-5.17; P < .001), and advanced maternal body mass index (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .012). Every additional unit of body mass index increased the risk of isthmocele by 6%. In the subgroup of emergency cesarean delivery, longer duration of active labor increased the risk for isthmocele (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .032). There was no statistically significant difference in prevalence between the groups of elective and emergency cesarean delivery (P = .898). CONCLUSION: Based on sonohysterographic examination, maternal body mass index, gestational diabetes, and previous cesarean deliveries are associated with an increased risk for incomplete healing of the uterine incision.

Robotic-Assisted Infrarenal Para-aortic Lymphadenectomy in Gynecological Cancers: Technique and Surgical Outcomes.

OBJECTIVE: Mini-invasive surgery has essentially replaced open laparotomy in surgery for endometrial and cervical carcinoma. Of the procedures needed for a complete staging, especially para-aortic lymphadenectomy (PALND) is challenging to perform. The present study was undertaken to investigate the technical and surgical outcomes of robotic-assisted PALND for gynecological cancers in the setting of a tertiary university hospital in Finland. METHODS: This was a retrospective chart review of 283 robotic-assisted para-aortic lymphadenectomies using the single-docking transperitoneal technique performed at the Department of Obstetrics and Gynecology of Tampere University Hospital, in 2009-2016. The primary outcome measure was the extent of the operation in terms of the height, that is, how often the level cranial to the inferior mesenteric artery (IMA) was achieved. The secondary outcome measures included operation time and surgical outcome. RESULTS: The majority of operations (n = 239 [84.4%]) were performed for endometrial carcinoma. The most common operation type was robotic-assisted hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy and PALND, which took a median of 3:38 hours or 218 minutes (range, 140-341 minutes) to perform. The high PALND (above the level of IMA) succeeded in 235 operations (83%). In the total cohort, the median number of para-aortic lymph nodes removed was 12 (range, 0-38), with a learning curve approximately more than 40 operations. Para-aortic lymph node metastases were found in 43 patients (15.2%). Seven conversions to laparotomy (2.5%) were done. The conversion and intraoperative complication rates were 2.5% and 3.5%, respectively, and postoperative complications was 18%, according to the classification of Clavien-Dindo. The median length of the postoperative hospital stay was 2 days (range, 1-8 days). CONCLUSIONS: Using the transperitoneal technique for PALND, the area between IMA and the renal veins can be reached in more than 80% of the operations, with a very low or 2.5% conversion rate.

Costs of Robotic-Assisted Versus Traditional Laparoscopy in Endometrial Cancer.

OBJECTIVES: The purpose of this study was to compare the costs of traditional laparoscopy and robotic-assisted laparoscopy in the treatment of endometrial cancer. METHODS AND MATERIALS: A total of 101 patients with endometrial cancer were randomized to the study and operated on starting from 2010 until 2013, at the Department of Obstetrics and Gynecology of Tampere University Hospital, Tampere, Finland. Costs were calculated based on internal accounting, hospital database, and purchase prices and were compared using intention-to-treat analysis. Main outcome measures were item costs and total costs related to the operation, including a 6-month postoperative follow-up. RESULTS: The total costs including late complications were 2160 &OV0556; higher in the robotic group (median for traditional 5823 &OV0556;, vs robot median 7983 &OV0556;, P < 0.001). The difference was due to higher costs for instruments and equipment as well as to more expensive operating room and postanesthesia care unit time. Traditional laparoscopy involved higher costs for operation personnel, general costs, medication used in the operation, and surgeon, although these costs were not substantial. There was no significant difference in in-patient stay, laboratory, radiology, blood products, or costs related to complications. CONCLUSIONS: According to this study, robotic-assisted laparoscopy is 37% more expensive than traditional laparoscopy in the treatment of endometrial cancer. The cost difference is mainly explained by amortization of the robot and its instrumentation.

Robotic-assisted vs traditional laparoscopic surgery for endometrial cancer: a randomized controlled trial.

BACKGROUND: Previous studies comparing robotic-assisted laparoscopic surgery to traditional laparoscopic or open surgery in gynecologic oncology have been retrospective. To our knowledge, no prospective randomized trials have thus far been performed on endometrial cancer. OBJECTIVE: We sought to prospectively compare traditional and robotic-assisted laparoscopic surgery for endometrial cancer. STUDY DESIGN: This was a randomized controlled trial. From December 2010 through October 2013, 101 endometrial cancer patients were randomized to hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy either by robotic-assisted laparoscopic surgery or by traditional laparoscopy. The primary outcome measure was overall operation time. The secondary outcome measures included total time spent in the operating room, and surgical outcome (number of lymph nodes harvested, complications, and recovery). The study was powered to show at least a 25% difference in the operation time using 2-sided significance level of .05. The differences between the traditional laparoscopy and the robotic surgery groups were tested by Pearson χ2 test, Fisher exact test, or Mann-Whitney test. RESULTS: In all, 99 patients were eligible for analysis. The median operation time in the traditional laparoscopy group (n = 49) was 170 (range 126-259) minutes and in the robotic surgery group (n = 50) was 139 (range 86-197) minutes, respectively (P < .001). The total time spent in the operating room was shorter in the robotic surgery group (228 vs 197 minutes, P < .001). In the traditional laparoscopy group, there were 5 conversions to laparotomy vs none in the robotic surgery group (P = .027). There were no differences as to the number of lymph nodes removed, bleeding, or the length of postoperative hospital stay. Four (8%) vs no (0%) patients (P = .056) had intraoperative complications and 5 (10%) vs 11 (22%) (P = .111) had major postoperative complications in the traditional and robotic surgery groups, respectively. CONCLUSION: In patients with endometrial cancer, robotic-assisted laparoscopic surgery was faster to perform than traditional laparoscopy. Also total time spent in the operation room was shorter in the robotic surgery group and all conversions to laparotomy occurred in the traditional laparoscopy group. Otherwise, the surgical outcome was similar between the groups. Robotic surgery offers an effective and safe alternative in the surgical treatment of endometrial cancer.

Hysterectomies in Finland in 1990-2012: comparison of outcomes between trainees and specialists.

OBJECTIVE: To assess trends for hysterectomy methods in the Nordic countries and to compare outcomes of hysterectomies in Finland done by trainees with those done by specialists. DESIGN: Register-based study. SETTING: NOMESCO database for the Nordic countries and the Finnish Hospital Discharge Register. POPULATION: National prospective cohort of 5279 hysterectomies in Finland. METHODS: Numbers of hysterectomies in the Nordic countries were collected in 1995-2011 and in Finland in 1990-2012. The Finhyst study to collect data on hysterectomies for benign indications was carried out in Finland in 2006. Information concerning patients, surgeons, and hysterectomy outcome was analysed. MAIN OUTCOME MEASURES: Hysterectomy numbers and methods. Operating time, blood loss, and complications in hysterectomies done by trainees and specialists. RESULTS: In Finland, the rate of hysterectomies has been reduced by approximately 50% since the 1990s and is now similar to that in the other Nordic countries. The laparoscopic method is twice as common in Finland as in other Nordic countries, constituting 35-40% of all hysterectomies. The operating time for all hysterectomy methods was 16-25% longer among trainees than specialists. For the abdominal or laparoscopic methods there were no significant differences in the complication rates between the groups. In the vaginal approach, blood loss of ≥1000 mL was slightly more common in operations done by trainees (1.3% vs. 2.6%, p = 0.037). CONCLUSIONS: Laparoscopic hysterectomy is more common in Finland than in the other Nordic countries. Although trainees need more time to operate, there were no differences between the trainees and the specialists with regard to major complication rates.

Implementing robotic surgery to gynecologic oncology: the first 300 operations performed at a tertiary hospital.

OBJECTIVE: To investigate the initial experience with robotic-assisted laparoscopic surgery in gynecologic oncology. DESIGN: A retrospective survey. SETTING: Tertiary referral center. POPULATION: The first 300 patients operated on using robotic assistance at the Department of Obstetrics and Gynecology of Tampere University Hospital, from March 2009 through January 2013. METHODS: Retrospective patient chart review. MAIN OUTCOME MEASURES: The primary outcome measure was the learning curve events, and the complication and conversion rates were secondary outcome measures. RESULTS: The commonest type of operation was hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy (LH + BSO + PLND, n = 89), followed by the same procedure amended by para-aortic lymphadenectomy (PALND, n = 74), type II radical hysterectomy (n = 24), and PLND + PALND ± omentectomy (n = 15). A learning curve was most evident for LH + BSO + PLND: whereas the median operative time of all 89 operations was 167 min (range 403-104), it was 260 (range 403-135) and 153 (range 247-104) min in the case of the first and last 20 operations, respectively. The learning curve was short, or 10 procedures. A learning curve was also seen for the preoperative time in the operation room and for the number of lymph nodes harvested. The median blood loss during all 300 operations was 100 mL (range 5-3200). The median postoperative hospital stay was 1 day. The conversion rate was 4.0%, and the complication rate 19.3% (major in 9%). CONCLUSION: The learning curve of robotic-assisted laparoscopic surgery appears to be short, or 10 operations. Robotic-assisted procedures seem to offer a safe and useful alternative to traditional techniques.

Autologous adipose stem cells in treatment of female stress urinary incontinence: results of a pilot study.

The purpose of our study was to find out whether transurethral injections of autologous adipose stem cells (ASCs) are an effective and a safe treatment for female stress urinary incontinence (SUI). We treated five SUI patients with ASCs combined with bovine collagen gel and saline. Prior to the treatment, the ASCs were isolated from subcutaneous fat and expanded for 3 weeks in a good manufacturing practice-level laboratory. The mixture of ASCs and collagen was injected transurethrally via cystoscope. Additionally, viability, multipotency, and surface marker profile of ASCs were analyzed in vitro. We followed up with patients 3, 6, and 12 months after the injections. The primary endpoint was a cough test to measure objectively the effect of the treatment. Validated questionnaires were used to determine the subjective cure rate. After 6 months, 1 of 5 patients displayed a negative cough test with full bladder filled with 500 ml of saline. At 1 year, the cough test was negative with three patients; two of them were satisfied with the treatment and did not wish further treatment for SUI. Validated questionnaires showed some subjective improvement in all five patients. This is the first study describing the use of autologous ASCs in combination with collagen gel for female SUI treatments. Thus far, the treatment with autologous ASCs has proven safe and well tolerated. However, the feasibility and efficacy of the treatment were not optimal; therefore, additional research is needed to develop SUI injection therapies.

Ten years of progress--improved hysterectomy outcomes in Finland 1996-2006: a longitudinal observation study.

OBJECTIVES: To study the outcome of various hysterectomies in 2 years 1996 (N =10110) and 2006 (N=5279). The hypothesis was that the change in operative practices in 10 years has resulted in improvements. DESIGN: 2 prospective nationwide cohort evaluations with the same questionnaire. SETTING: All national operative hospitals in Finland. PARTICIPANTS: Patients scheduled to either abdominal hysterectomy (AH), vaginal hysterectomy (VH) or laparoscopic hysterectomy (LH) for benign disease. OUTCOME MEASURES: Patients' characteristics, surgery-related details and complications (organ injury, infection, venous thromboembolism and haemorrhage). RESULTS: The overall complication rates fell in LH and markedly in VH (from 22.2% to 11.7%, p<0.001). The overall surgery-related infectious morbidity decreased in all groups and significantly in VH (from 12.3% to 5.2%, p<0.001) and AH (from 9.9% to 7.7%, p<0.05). The incidence of bowel lesions in VH sank from 0.5% to 0.1% and of ureter lesions in LH from 1.1% to 0.3%. In 2006 there were no deaths compared with three in 1996. CONCLUSIONS: The rate of postoperative complications fell markedly in the decade from 1996 to 2006. This parallels with the recommendation of the recent meta-analyses by Cochrane collaboration; the order of preference of hysterectomies was for the first time precisely followed in this nationwide study. TRIAL REGISTRATION: The 2006 study was registered in the Clinical Trials of Protocol Registration System Data (NCT00744172).

Carbonic anhydrase isozymes II, IX, and XII in uterine tumors.

Histopathological diagnostics of gynecological malignancies continues to be challenging despite the well established criteria. For example, the morphological distinction of uterine leiomyosarcoma from certain variants of benign leiomyoma can be difficult. Herein, we investigated the expression of Carbonic anhydrase (CA) II, IX, and XII in the normal endometrium, leiomyomas, uterine sarcomas, and endometrial adenocarcinomas using immunohistochemistry. These isozymes are considered promising diagnostic markers and therapeutic targets. The normal endometrium showed high CA XII expression, whereas the signals were lower in endometrial adenocarcinoma (p < 0.004). Only sporadic CA IX staining was found in the normal endometrium, whereas the enzyme was overexpressed in most cases of endometrial adenocarcinoma (p < 0.005). CA II expression was slightly weaker in the normal endometrium than that in the adenocarcinomas (p < 0.008). Positive immunostaining reactions for CAs were observed in the uterine sarcomas, whereas all leiomyomas were negative for CA II and XII. A comparison between leiomyomas and sarcomas showed statistically significant differences for all studied isozymes (p < 0.001). Our study shows that CA isozymes could together serve as histopathological biomarkers for differential diagnosis between uterine leiomyosarcoma and leiomyoma. In addition to being found in leiomyosarcomas, CA II and IX were overexpressed in endometrial adenocarcinoma, where they might regulate the pH of the tumor microenvironment.

[Robotic surgery in gynecology]. / Robotti gynekologisessa kirurgiassa.

Small surgical wounds are just one of the benefits of laparoscopic surgery. Laparoscopic surgery is, however, technically challenging for the surgeon. Learning requires extensive practice, and working postures are tiring. Surgical robot is the latest advance. The benefits provided by the robot--three-dimensional stable view into the surgical target, easily guided flexible instruments and ergonomic working posture--offer significant benefits in several indications.

FINHYST 2006--national prospective 1-year survey of 5,279 hysterectomies.

BACKGROUND: In Finland, the number of hysterectomies during one decade has decreased by 34%. The national prospective FINHYST study in 1996 showed abdominal hysterectomy (AH) as being most common: 58%. In Finland since 2002, vaginal hysterectomy (VH) has been most preferred, with laparoscopic hysterectomy (LH) surpassing AH in 2005. METHODS: FINHYST 2006 is a national prospective hysterectomy study in which all hospitals collaborated from 1 January to 31 December 2006. Questionnaires, completed by gynaecologists, covered their experience, patient characteristics and surgical data. RESULTS: The 5279 hysterectomies distributed by approaches were 44% VHs, 32% LHs and 24% AHs. Less than 2% were subtotal. The main indications for hysterectomy were myomas (33%), uterine prolapse (28%) and menorrhagia (21%). The main indication for VH was not related to uterine prolapse in 39%. Bilateral salpingo-ooforectomy was performed in 36% of AHs, 32% of LHs and 2% of VHs. Antibiotic prophylaxis was used in 97%, and thrombosis prophylaxis in 65%. Haemorrhage was least and operation time shortest with VH, and hospital stay and sick leave were shortest after LH. CONCLUSIONS: In Finland, less invasive approaches comprise 76% of hysterectomies. This trend has resulted nationally in shortening of hospital stay and of convalescence time.

Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy.

OBJECTIVE: Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer. STUDY DESIGN: A total of 156 patients with Stage IA-B Grade 3 (n=28), or Stage IC-IIIA Grade 1-3 (n=128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n=72) or radiotherapy combined with three courses of cisplatin (50 mg/m(2)), epirubicin (60 mg/m(2)) and cyclophosphamide (500 mg/m(2)) (Group B, n=84). RESULTS: The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B (p=0.148). The median disease-free survival in A was 18 (range 9-36) months and 25 (range 12-49) months in B (p=0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6-37) months in Group A, and 20 (range 8-60) months in Group B, respectively (p=0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15-44) months as compared to 37 (range 13-50) months in B (p=0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively. CONCLUSION: Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications.

Endometrial K-ras mutations in postmenopausal breast cancer patients treated with adjuvant tamoxifen or toremifene.

PURPOSE: Long-term use of tamoxifen is associated with a two- to threefold increased risk of endometrial cancer in postmenopausal women. Toremifene is another triphenylethylene antiestrogen, which is as effective as tamoxifen in postmenopausal breast cancer. Thus far, its use has not been associated with an increased risk of endometrial cancer. K-ras codon 12 mutations seem to be important in endometrial carcinogenesis, and these mutations have been found in endometrial samples of patients on tamoxifen. The present study was undertaken to investigate if there is any difference in the frequency of endometrial K-ras mutations among patients treated with tamoxifen or toremifene. METHODS: Endometrial samples were taken from 23 postmenopausal breast cancer patients (tamoxifen, n = 11; toremifene, n = 12) before and after 36 months of treatment. DNA was isolated from formalin-fixed paraffin-embedded samples using a routine proteinase K digestion protocol. K-ras mutations in codon 12 were screened using real-time PCR and melting curve analysis in LightCycler equipment. Wild-type PNA oligomer was used to increase the sensitivity of the assay. RESULTS: All baseline samples contained wild-type K-ras, while 10/23 (43%) of the follow-up samples carried a codon 12 mutation. Mutations were identified in 3 of the 11 in the tamoxifen group and in 7 of the 12 in the toremifene group. Seven were transitions (G-->A), and three were transversions (two G-->T, one G-->C). One of the mutations in the toremifene group was associated with a polypoid endometrium. All the other mutations were found in an atrophic (n = 6) or proliferative (n = 3) endometrium. CONCLUSIONS: Both tamoxifen and toremifene induce endometrial K-ras codon 12 mutations. The significance of this finding to endometrial carcinogenesis remains to be elucidated.

Expression of nuclear receptors and cofactors in human endometrium and myometrium.

OBJECTIVE: To study the expression of nuclear receptors and cofactors in human endometrium and myometrium in proliferative and secretory phases of the menstrual cycle. METHODS: Multiprobe ribonuclease protection assay and real-time reverse transcriptase polymerase chain reaction were used to quantitate mRNA levels of steroid receptors, vitamin D receptor (VDR), retinoic acid receptors (RAR), and cofactors AIB1 (amplified in breast cancer-1), CBP (cyclic adenosine monophosphate response element binding protein), pCAF (p300/CBP-associated factor), TIF2 (transcription intermediary factor-2), N-CoR (nuclear receptor corepressor), and SMRT (silencing mediator of repressed transcription). Cyclin A expression was analyzed to determine the proliferation status of the tissues. RESULTS: The expression of androgen receptor, estrogen receptors alpha and beta, progesterone receptor, and RARalpha followed cyclin A expression. There was more abundant expression in the proliferative phase endometrium than in the secretory phase endometrium. Glucocorticoid receptor, VDR, RARbeta, and RARgamma were stably expressed during the menstrual cycle in both endometrium and myometrium. Cofactors N-CoR, SMRT, pCAF, CBP, TIF2, AIB1, and p300 mRNAs were expressed in all samples in both endometrium and myometrium. N-CoR, pCAF, AIB1, and p300 appeared not to be regulated when comparing proliferative and secretory phases of the cycle. Individual differences were found in the expression levels of both nuclear receptors and cofactors. CONCLUSION: The menstrual cycle-dependent regulation of nuclear receptor expression was more apparent in the endometrium than in the myometrium, whereas cofactor expression was not cycle dependent. There were individual differences in the expression levels of different receptors and cofactors. In hormonal therapy these differences might result in different responses, depending on the patient as well as the ligand used.

Clinical outcome and complications of laparoscopic surgery compared with traditional surgery in women with endometrial cancer.

INTRODUCTION: The purpose of this study was to evaluate the feasibility, clinical outcome and complications of laparoscopic surgery in women with endometrial cancer and to compare surgical outcome and postoperative early and late complications with results of traditional laparotomy. METHODS: Forty women with endometrial cancer underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Each patient operated by laparoscopy was matched by age, preoperative clinical stage and histology of the endometrial cancer with a patient treated by the same operation but using traditional laparotomy. Half of these patients underwent total pelvic lymphadenectomy and half had pelvic lymph node sampling. The groups were compared in clinical characteristics, surgical outcomes, recoveries and early and late postoperative complications. RESULTS: The patients in the laparoscopy group had less blood loss, more lymph nodes removed, shorter hospital stay but longer operation time than those treated by laparotomy. Only one (2.5%) laparoscopy was converted to laparotomy due to pelvic adhesions. There were no intraoperative complications in either group. Postoperative complications were more common (55.0%) in the laparotomy than in the laparoscopy group (37.5%). Only one major complication (2.5%) occurred among patients undergoing laparoscopy as compared with three (7.5%) major complications in the laparotomy group. Superficial wound infection was the most common (20%) infection in laparotomy patients while vaginal cuff cellulitis occurred in 10% of laparoscopy patients. Late (>42 days) postoperative complications were almost equally frequent (20.0 and 22.5%) in both groups. Lower extremity lymph edema or pelvic lymph cyst was found in 12.5% of all cases. As a result of surgical staging the disease of 6 women (15%) in both groups was upgraded. CONCLUSIONS: Laparoscopic surgery is a viable alternative to traditional surgery in the management of endometrial cancer. The surgical outcome is similar in both cases. In laparoscopic procedures the operation time is longer but the postoperative recovery time shorter than in laparotomy. Severe complications were limited in both groups, while wound infections can be avoided using laparoscopy.

Tension-free vaginal tape and laparoscopic mesh colposuspension in the treatment of stress urinary incontinence: immediate outcome and complications--a randomized clinical trial.

BACKGROUND: The purpose of the study was to evaluate the immediate outcome and complications of the tension-free vaginal tape (TVT) and laparoscopic mesh colposuspension (LC) procedures in the treatment of female stress urinary incontinence (SUI). METHODS: One hundred and twenty-eight patients suffering from urodynamically confirmed SUI were recruited to this multicenter, randomized clinical trial. After randomization there were seven drop-outs--121 patients were operated upon: 70 patients in the TVT group and 51 in the LC group. The patients were evaluated according to the study protocol before operation and 6 weeks after it. The independent sample t-test and the Mann-Whitney U-test were used to calculate statistical differences between the study groups. RESULTS: Immediate cure rates, defined as negative stress test with 300 mL saline in the bladder, were similar (92.9% in the TVT group and 88.2% in the LC group; p = ns). Return to normal voiding was faster in the TVT group (9.2 h in the TVT group vs. 24.4 h in the LC group; p = 0.004). Fewer analgesics were used in the TVT group and hospital stay was shorter in this group. Complication rates associated with the procedures were similar and the number of complications was small. CONCLUSIONS: The immediate outcome of both procedures is the same. The rates of complications were similar. However, the TVT procedure seems to be less invasive and requires fewer hospital resources than LC.