Jyrki Jalkanen

FINHYST, a prospective study of 5279 hysterectomies: complications and their risk factors

BACKGROUND Hysterectomy guidelines highlight an increase in urinary tract injuries with laparoscopic hysterectomy (LH). This national survey analyses complications of LH, abdominal hysterectomy (AH) and vaginal hysterectomy (VH). METHODS A prospective cohort undergoing hysterectomy for benign indications during 2006 was drawn from 53 hospitals in Finland; all communal hospitals participated. Detailed questionnaires covered surgical data and intra- and post-operative major and minor complications, for which risk factors were analysed by a multivariate logistic regression model adjusted for surgical data and patient characteristics. RESULTS Major complications rates in AH (n= 1255, 24%), LH (1679, 32%) and VH (2345, 44%) were 4.0, 4.3 and 2.6%, and total complications rates were 19.2, 15.4 and 11.7%, respectively. Logistic regression showed no statistically significant differences between approaches for any organ injuries or other major complications. Most bladder and bowel injuries (88 and 83%), but not ureter injuries (10%), were recognized intra-operatively. The ureter injury rate was low after LH (0.3%), as it was after other types of hysterectomy. Compared with LH, AH increased the odds of wound infection, and was an independent risk factor for urinary infections and febrile events. Compared with AH, LH and VH both presented a higher risk for pelvic infection; surgically treated equally often regardless of the type of hysterectomy. No differences in complications emerged between LH and VH. Obesity was a risk factor for many infections. Surgical adhesiolysis [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.38-4.21] was the strongest single risk factor for major complications as a whole. Bladder injury was associated with a history of caesarean section (OR 4.01, 95% CI 2.06-7.83) and with a large uterus ≥500 g (OR 2.88, 95% CI 1.05-7.90), while bowel injury was associated with adhesiolysis (OR 29.07, 95% CI 7.17-117.88). CONCLUSIONS FINHYST is a large prospective hysterectomy study illustrating actual complications. Whenever possible, hysterectomy should be minimally invasive.

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.

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).

Pharmaceutical thrombosis prophylaxis, bleeding complications and thromboembolism in a national cohort of hysterectomy for benign disease

BACKGROUND Pharmaceutical thrombosis prophylaxis (PTP) with low-molecular-weight heparin (LMWH) is highly effective in preventing venous thromboembolic events (VTEs) and fatal pulmonary embolism. Important risk factors for VTEs are surgery and immobilization, along with malignancy. Many studies involving gynaecological malignancies show no increased risk for bleeding complications with PTP. Little is known about the PTP-associated risk for bleeding complications with hysterectomy for benign disease, or about current VTE incidence in the less-invasive hysterectomy methods. METHODS Our observational prospective national 1-year cohort from 1 January to 31 December 2006 in 53 hospitals represented 79.4% (5297 of 6645) of hysterectomies performed for benign cause in Finland in 2006. We evaluated PTP use and VTE incidence. Operative and post-operative bleeding complications were analysed with logistic regression adjusted for confounders: age, BMI, experience of the gynaecological surgeon, hospital type, indication for hysterectomy, uterine weight, operative haemorrhage, concomitant surgery, adhesiolysis and antibiotic prophylaxis. RESULTS Hysterectomies were performed by three main approaches: 2345 vaginal hysterectomies (VHs, 44%), of which 1433 were for uterine prolapse and 912 for other indications, 1679 laparoscopic hysterectomies (LHs, 32%) and 1255 abdominal hysterectomies (AHs, 24%). PTP was given to 64.8% of patients (3420 of 5279) and was identified as LMWH in 3313 patients (97%); 107 left unidentified. By type of hysterectomy, PTP was given in VH for uterine prolapse to 73.2% of patients, VH for other indication to 51.6%, in LH to 59.4% and in AH to 71.9%. For all hysterectomies analysed together, PTP doubled the odds for post-operative haemorrhage or haematoma. By type of hysterectomy, PTP associated with post-operative haemorrhage or haematoma in VH for prolapse [2.7% of PTP given, versus 0.8% of no PTP; odds ratio (OR): 4.82, 95% confidence interval (CI): 1.38-16.83]; and in AH (3.1% versus 1.4%; OR: 2.87, 95% CI: 1.03-7.98), and in AH also with post-operative transfusion (3.1% versus 1.4%; OR: 3.34, 95% CI: 1.41-7.88). For LH and VH for indications other than prolapse, the effect of PTP on post-operative haemorrhage was non-significant. For VH, the risk for post-operative haemorrhage fell with age. Operative mean haemorrhage with all hysterectomy types, and operative bleeding complications in AH and VH also fell with age. Obesity increased haemorrhage and operative bleeding complications for LH and VH, whereas post-operative bleeding complications were less for the obese in AH. VTEs were 6 of 5279 (0.1%): two PEs each occurred after AH and VH, and two deep venous thromboses after LH. CONCLUSIONS With a relatively wide PTP coverage (64.8%), VTEs were rare (0.1%). All affected had received PTP. Analysis of efficacy, meaning interpretation of how many VTEs or deaths were prevented, cannot be done from our observational study but related to safety in hysterectomy for benign disease, PTP associated with post-operative bleeding complications with AH and with VH for prolapse. TRIAL REGISTRATION NUMBER ClinicalTrials.gov protocol (NCT00744172).

Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole, or both?

To evaluate cefuroxime and metronidazole antibiotic prophylaxis.

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

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.

Interaction of 17β-estradiol and progesterone production in human granulosa-luteal cells

The secretion of 17 beta-estradiol (E2) and the effect of exogenous E2 on progesterone (P) production by granulosa-luteal cells from 18 women attending an in vitro fertilization (IVF) program were studied. The cells were separated from follicular fluid and precultured in medium containing fetal calf serum. On the third day of culture E2 (0.25-2.0 micrograms/ml) was added onto the cells and its effect on both hCG-stimulated and basal P production was measured. E2 inhibited both basal and hCG-stimulated P production. 1 microgram/ml of E2 caused mean decrements of 55 and 56% in basal and hCG-stimulated P production, respectively. The maximal inhibition by E2 occurred at 6 hours of incubation, but when the cells were allowed to react with E2 for longer periods of time the effect became less significant and more variable. At 48 h no inhibition was observed. At 6 h E2 (1.0 microgram/ml) increased both basal and hCG-stimulated pregnenolone production by approx. 10-fold, suggesting that the suppression of P production was due to inhibition of 3 beta-hydroxysteroid dehydrogenase. Exogenous androgen, 5-Androsten-3 beta-ol-17-one sulfate, dehydroepiandrosterone sulfate (DHEAS), in a dose-dependent manner increased granulosa-luteal cell E2 production. The maximal response was about 1000-fold above the E2 production of unstimulated cells and was not affected by hCG. However, the maximal amount of E2 produced was minor in comparison to exogenous doses required for the suppression of P production and did not have the inhibitory effect. It is concluded that the production of E2 by granulosa-luteal cells is mainly regulated by the availability of androgen substrate, and that E2 functions as a modulator of luteal P production.

Validation of the short forms of the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) in Finnish

BackgroundAlthough several validated generic health-related quality of life instruments exist, disease-specific instruments are important as they are often more sensitive to changes in symptom severity. It is essential to validate the instruments in a new population and language before their use. The objective of the study was to translate into Finnish the short forms of three condition-specific questionnaires (PFDI-20, PFIQ-7 and PISQ-12) and to evaluate their psychometric properties in Finnish women with symptomatic pelvic organ prolapse.MethodsA multistep translation method was used followed by an evaluation of validity and reliability in prolapse patients. Convergent and discriminant validity, internal consistency and reliability via test-retest were calculated.ResultsSixty-three patients waiting for prolapse surgery filled the three questionnaires within two weeks. Response rate for each item was high in PFDI-20 and PISQ-12 (99.8 and 98.9% respectively). For PFIQ-7 response rate was only 60%. In PFIQ-7, six respondents (9.5%) reached the minimum value of zero showing floor effect. None of the instruments had ceiling effect. Based on the item-total correlations both PFIQ-7 and PFDI-20 had acceptable convergent validity, while the convergent validity of PISQ-12 was lower, r = 0.138–0.711. However, in this instrument only three questions (questions 6, 10 and 11) had r < 0.3 while others had r ≥ 0.380. In the test-retest analysis all the three instruments showed good reliability (ICC 0.75–0.92). Similarly, the internal consistency of the instruments, measured by Cronbach’s α, was good (range 0.69–0.96) indicating high homogeneity.ConclusionsFinnish validated translation of the PFDI-20 and PISQ-12 have acceptable psychometric properties and can be used for both research purposes and clinical evaluation of pelvic organ prolapse symptoms. The Finnish version of PFIQ-7 displayed low response rate and some evidence of a floor effect, and thus its use is not recommended in its current form.

Abstract 120: Estrogen and progesterone receptor expression in different molecular uterine leiomyoma subclasses

Uterine leiomyomas (ULs) are benign, estrogen- and progesterone-dependent smooth muscle tumors of the uterus. They are among the most common human neoplasms with an estimated prevalence of 20-40% in women of reproductive age, but also percentages as high as 77% have been reported. Although benign, ULs form a major burden to women9s health. Approximately 25% of women with ULs have clinically relevant lesions, which cause morbidity and thus require treatment. As a consequence, ULs are the leading cause of hysterectomy worldwide. Despite the high prevalence and socio-economic impact of ULs, the molecular mechanisms underlying the growth and development of these lesions remain largely unknown. Familial, epidemiological, and cytogenetic studies indicate that genetic factors play a central role in the development of these lesions. Our recent findings, derived from the use of high-throughput technologies, have pointed to at least three distinct molecular UL subclasses, each candidate subclass displaying a characteristic genetic driver aberration as well as global gene expression profile: MED12 (mediator complex subunit 12) mutation-positive, HMGA2 (high mobility group AT-hook 2)-overexpressing, and FH (fumarate hydratase)-deficient ULs. Although the majority of ULs show estrogen and progesterone receptor (ER and PR) positivity on protein level, a subgroup of these tumors are ER- or PR-negative with an estimated frequency of up to 10%. The aim of this study is to assess the potential correlation between steroid receptor expression and different molecular UL subclasses. The study material consists of 1100 ULs collected from hysterectomy patients during surgery in Helsinki University Central Hospital and Central Finland Central Hospital, Finland. All ULs are systematically screened for MED12 mutations by Sanger sequencing. Because overexpression of HMGA2 typically arises through a chromosomal translocation, HMGA2-overexpressing ULs as well as FH-deficient tumors are tentatively identified using a high-density customizable Infinium® HumanCore-24+ BeadChip with 4000 additional custom markers that cover known genes, candidate regions, and single-nucleotide variations related to UL genesis. Also ULs without any known genetic driver aberrations are included in the study. ER and PR protein expression are analyzed by immunohistochemistry. Currently, molecular classification of the tumors plays no role in choosing treatment, but ULs are treated as a single entity. Different molecular subclasses may, however, use different molecular pathways, have different clinical outcome, or response to treatment. Identification of ER- and PR-negative ULs and their potential association with the genetic driver aberrations may provide important new information on the molecular mechanisms underlying UL genesis. Increased knowledge is also essential for developing new targeted treatments and improving management of the condition. Citation Format: Netta Makinen, Annukka Pasanen, Hanna-Riikka Heinonen, Kati Kampjarvi, Simona Bramante, Miika Mehine, Jyrki Jalkanen, Oskari Heikinheimo, Jari Sjoberg, Ralf Butzow, Lauri Aaltonen. Estrogen and progesterone receptor expression in different molecular uterine leiomyoma subclasses. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 120.