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1.
Arch Gynecol Obstet ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976021

ABSTRACT

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.

2.
Am J Obstet Gynecol ; 230(6): 651.e1-651.e17, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38365101

ABSTRACT

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.


Subject(s)
Endometriosis , Mental Disorders , Registries , Humans , Female , Endometriosis/epidemiology , Endometriosis/complications , Finland/epidemiology , Longitudinal Studies , Adult , Young Adult , Mental Disorders/epidemiology , Retrospective Studies , Cause of Death , Proportional Hazards Models , Cohort Studies , Suicide/statistics & numerical data , Anxiety Disorders/epidemiology , Violence/statistics & numerical data , Accidents , Adolescent , Bipolar Disorder/epidemiology , Ovarian Diseases/epidemiology , Ovarian Diseases/mortality , Depressive Disorder/epidemiology
3.
Acta Obstet Gynecol Scand ; 102(12): 1634-1642, 2023 12.
Article in English | MEDLINE | ID: mdl-37814355

ABSTRACT

INTRODUCTION: Chronic pelvic pain (CPP) affects over one fifth of women worldwide, and endometriosis is one of the most common causes. In the present study, we examined whether sacral neuromodulation (SNM) is effective in the treatment of refractory chronic pelvic pain in women with endometriosis. MATERIAL AND METHODS: This multicenter prospective pilot study was started in 2017 and includes patients with chronic pelvic pain with no other obvious pathology than endometriosis. Other treatment options have been tried or they are unsuitable. Patients underwent SNM implantation. The main outcome was postoperative pain reduction and secondary outcome was quality of life. The following questionnaires were used to assess the outcomes: Brief pain inventory (BPI), clinical global impression - improvement (CGI-I), 15D-measure of health-related quality of life, and Biberoglu and Behrman (B&B) score. RESULTS: A total of 35 patients underwent the SNM procedure and, at the time of analysis, 15 patients had returned one-year questionnaires. The patients had a history of endometriosis for a median of 5.5 (interquartile range 2-9) years, with no correlation between the severity of symptoms and the duration of the disease (p = 0.158). A total of 31 patients (89%) were implanted with the internal pulse generator. There were statistically significant changes in BPI pain-related items. Worst experienced daily pain decreased among those who returned 12-month questionnaires from median 9 to 5 (p = 0.006), average daily pain from 6 to 3.5 (p = 0.004), and least daily pain from 3 to 1 (p = 0.004). Based on the CGI questionnaire (n = 14), at 12 months nine patients (60%) experienced great improvement in their symptoms, three patients (20%) much improvement and two patients (13%) minimal improvement. None of the patients experienced worsening of their symptoms. There was a statistically significant change in overall 15D score at 1 month (p < 0.001), 6 months (p = 0.001) and 12 months (p = 0.018), when the results were compared to baseline values. Median B&B score also improved significantly and decreased from a baseline value of 8 (4-12) to 4.5 (0-6), p = 0.002. CONCLUSIONS: Based on the preliminary findings of our study, SNM might be a promising treatment of CPP in endometriosis patients.


Subject(s)
Chronic Pain , Electric Stimulation Therapy , Endometriosis , Humans , Female , Endometriosis/complications , Endometriosis/therapy , Prospective Studies , Quality of Life , Pilot Projects , Pelvic Pain/etiology , Pelvic Pain/therapy , Treatment Outcome , Chronic Pain/etiology , Chronic Pain/therapy
4.
Acta Obstet Gynecol Scand ; 102(5): 556-566, 2023 05.
Article in English | MEDLINE | ID: mdl-37014706

ABSTRACT

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.


Subject(s)
Hysterectomy , Pelvic Organ Prolapse , Female , Humans , Male , Follow-Up Studies , Retrospective Studies , Hysterectomy/adverse effects , Hysterectomy, Vaginal , Pelvic Organ Prolapse/surgery , Pelvic Organ Prolapse/etiology
5.
Nat Genet ; 55(3): 423-436, 2023 03.
Article in English | MEDLINE | ID: mdl-36914876

ABSTRACT

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.


Subject(s)
Endometriosis , Female , Humans , Endometriosis/genetics , Endometriosis/metabolism , Genetic Predisposition to Disease , Genome-Wide Association Study , Pain , Comorbidity
6.
Genes Chromosomes Cancer ; 62(1): 27-38, 2023 01.
Article in English | MEDLINE | ID: mdl-35822448

ABSTRACT

Uterine leiomyomas, or fibroids, are very common smooth muscle tumors that arise from the myometrium. They can be divided into distinct molecular subtypes. We have previously shown that 3'RNA-sequencing is highly effective in classifying archival formalin-fixed paraffin-embedded (FFPE) leiomyomas according to the underlying mutation. In this study, we performed 3'RNA-sequencing with 111 FFPE leiomyomas previously classified as negative for driver alterations in mediator complex subunit 12 (MED12), high mobility group AT-hook 2 (HMGA2), and fumarate hydratase (FH) by Sanger sequencing and immunohistochemistry. This revealed 43 tumors that displayed expression features typically seen in HMGA2-positive tumors, including overexpression of PLAG1. We explored 12 such leiomyomas by whole-genome sequencing to identify their underlying genomic drivers and to evaluate the feasibility of detecting chromosomal driver alterations from FFPE material. Four tumors with significant HMGA2 overexpression at the protein-level served as controls. We identified chromosomal rearrangements targeting either HMGA2, HMGA1, or PLAG1 in all 16 tumors, demonstrating that it is possible to detect chromosomal driver alterations in archival leiomyoma specimens as old as 18 years. Furthermore, two tumors displayed biallelic loss of DEPDC5 and one tumor harbored a COL4A5-COL4A6 deletion. These observations suggest that instead of only HMGA2-positive leiomyomas, a distinct leiomyoma subtype is characterized by rearrangements targeting either HMGA2, HMGA1, or PLAG1. The results indicate that the frequency of HMGA2-positive leiomyomas may be higher than estimated in previous studies where immunohistochemistry has been used. This study also demonstrates the feasibility of detecting chromosomal driver alterations from archival FFPE material.


Subject(s)
Leiomyoma , Uterine Neoplasms , Female , Humans , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , HMGA1a Protein/genetics , Leiomyoma/genetics , Leiomyoma/pathology , HMGA2 Protein/genetics , HMGA2 Protein/metabolism , Fumarate Hydratase/genetics , Chromosome Aberrations , Mutation , Transcription Factors/genetics , RNA , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism
7.
Oncogenesis ; 11(1): 52, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36068196

ABSTRACT

Uterine leiomyomas, or fibroids, are the most common tumors in women of reproductive age. Uterine leiomyomas can be classified into at least three main molecular subtypes according to mutations affecting MED12, HMGA2, or FH. FH-deficient leiomyomas are characterized by activation of the NRF2 pathway, including upregulation of the NRF2 target gene AKR1B10. Here, we have identified a novel leiomyoma subtype showing AKR1B10 expression but no alterations in FH or other known driver genes. Whole-exome and whole-genome sequencing revealed biallelic mutations in key genes involved in neddylation of the Cullin 3-RING E3 ligase, including UBE2M, NEDD8, CUL3, and NAE1. 3'RNA sequencing confirmed a distinct molecular subtype with activation of the NRF2 pathway. Most tumors displayed cellular histopathology, perivascular hypercellularity, and characteristics typically seen in FH-deficient leiomyomas. These results suggest a novel leiomyoma subtype that is characterized by distinct morphological features, genetic alterations disrupting neddylation of the Cullin 3-RING E3 ligase, and oncogenic NRF2 activation. They also present defective neddylation as a novel mechanism leading to aberrant NRF2 signaling. Molecular characterization of uterine leiomyomas provides novel opportunities for targeted treatment options.

8.
Arch Gynecol Obstet ; 306(6): 2069-2075, 2022 12.
Article in English | MEDLINE | ID: mdl-36044047

ABSTRACT

PURPOSE: Hysterectomy and mid-urethral sling (MUS) are common operations, but little is known about how hysterectomy after MUS affects the risk for stress urinary incontinence (SUI) relapse. METHODS: We included 49 women with a MUS before hysterectomy and 41 women with a MUS concomitant with hysterectomy. The controls, matched by age (± 2 years), MUS type (retropubic vs transobturator) and operation year (± 2 years), included 201 women who underwent the MUS operation without a subsequent hysterectomy. We used health care registers for follow-up of 12.4 years in median (IQR 10.9-14.7) after the MUS operation to compare the number of SUI re-operations and hospital re-visits for urinary incontinence. RESULTS: The re-operation rates for SUI did not differ between the women with MUS before hysterectomy (n = 2, 4.1%), women with MUS concomitant with hysterectomy (n = 2, 4.9%) and their controls (n = 4, 4.9%, p = 0.8 and n = 6, 5.0%, p = 1.0, respectively). There were significantly fewer urinary incontinence re-visits among women who had a MUS concomitant with the hysterectomy compared to their matched controls (n = 2 and 31, 5 and 31%, p < 0.01) and to the women with a MUS prior to hysterectomy (n = 2 and 10, 5 and 20%, respectively, p = 0.03). CONCLUSION: Hysterectomy after or concomitant with MUS does not seem to increase the risk for SUI re-operation or hospital re-visits for urinary incontinence. These results can be used to counsel women considering hysterectomy after MUS operation or concomitant with MUS operation.


Subject(s)
Suburethral Slings , Urinary Incontinence, Stress , Urinary Incontinence , Female , Humans , Urinary Incontinence, Stress/surgery , Follow-Up Studies , Urologic Surgical Procedures/methods , Urinary Incontinence/surgery , Reoperation , Hysterectomy/adverse effects
9.
Acta Obstet Gynecol Scand ; 101(10): 1065-1073, 2022 10.
Article in English | MEDLINE | ID: mdl-35818936

ABSTRACT

INTRODUCTION: Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis-related procedures during the study period, 1987-2012. MATERIAL AND METHODS: In this register-based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age-specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person-years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios. RESULTS: Adolescents were divided into three age groups, <17, 17-18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 [72%] and 119/526 [23%], respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person-years varied from 5.63 (95% confidence interval [CI] 4.24-7.33) to 11.42 (95% CI 9.64-13.44). The incidence rate in 2001-2005 was significantly higher and was 1.6- to 2.0-fold that of the periods 1987-1990 and 2006-2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD-9; 1987-1995) and Tenth Revision (ICD-10; 1996-2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups. CONCLUSIONS: Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26-year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001-2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.


Subject(s)
Endometriosis , Adolescent , Cohort Studies , Cross-Sectional Studies , Endometriosis/diagnosis , Endometriosis/epidemiology , Endometriosis/surgery , Female , Finland/epidemiology , Humans , Incidence , Registries
10.
J Minim Invasive Gynecol ; 28(9): 1650-1655, 2021 09.
Article in English | MEDLINE | ID: mdl-33582379

ABSTRACT

STUDY OBJECTIVE: To compare the health-related quality of life (HRQoL) and psychologic distress after laparoscopic hysterectomy (LH) following enhanced recovery after surgery (ERAS) and conventional recovery protocols. DESIGN: A secondary analysis of a single-center randomized controlled trial. SETTING: University hospital. PATIENTS: Women assigned to LH were randomly divided into 2 groups: intervention (ERAS protocol) group (IG) (n = 60) and control (conventional protocol) group (CG) (n = 60). INTERVENTIONS: Women in the intervention group (IG) were treated according to the ERAS protocol. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a change in HRQoL assessed by the 15D questionnaire and a change in psychologic distress assessed by the General Health Questionnaire-12 at baseline before surgery and 1 month later. One month after surgery, the HRQoL was clinically and statistically better compared with baseline but with no difference between the groups. When following the ERAS protocol, the improvement in HRQoL was clinically greater, the difference in the dimension of sleeping was statistically better (p <.05), and the dimensions of discomfort and symptoms (+0.028), depression (+0.282), distress (+0.018), and vitality (+0.040) were clinically better than when following the conventional recovery protocol. No differences were found in the psychologic distress scores either preoperatively or 1 month after surgery (24 in IG vs 25 in CG [p = .85] and 9 in IG vs 12 in CG [p = .47], respectively). CONCLUSION: The HRQoL improved after LH with no significant difference between the ERAS and conventional recovery protocols. However, clinically, the change in HRQoL was greater, and the dimensions of sleeping, discomfort and symptoms, depression, distress, and vitality were better when following ERAS. Psychologic distress was equal in both groups. ERAS seems to have a positive impact on recovery after LH.


Subject(s)
Enhanced Recovery After Surgery , Laparoscopy , Female , Humans , Hysterectomy/adverse effects , Length of Stay , Quality of Life , Randomized Controlled Trials as Topic
11.
Fertil Steril ; 115(2): 406-415, 2021 02.
Article in English | MEDLINE | ID: mdl-33039131

ABSTRACT

OBJECTIVE: To study reproductive outcomes, and pregnancy and delivery complications after conservative or operative treatment of rectovaginal endometriosis during long-term follow-up. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Women with rectovaginal endometriosis referred to hospital due to any indication from 2004 to 2013 (N = 543) who were treated initially either conservatively (group CONS, n = 183), or operatively (OPER, n = 360) either with resection of rectovaginal nodule (RVR, n = 192) or with concomitant bowel resection (BR, n = 132). INTERVENTION(S): Conservative or operative management. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live-birth rate, and assessment of the complications during pregnancy and delivery. RESULTS(S): Between women in the CONS group or OPER group, no differences were found in either clinical pregnancy rate (56%, n = 102 vs. 50%, n = 181) or live-birth rate (48%, n = 87 vs. 42%, n = 153). Of the pregnancies, 64% (n = 65) and 49% (n = 89), respectively, started after medically assisted reproduction. No differences emerge in the subanalysis of women <40 years-old who wished to conceive. The most common pregnancy complication was preterm birth: 15% (n = 13) in the CONS group and 20% (n = 30) in the OPER group. The cesarean delivery rate also was high (46%, n = 40 vs. 49%, n = 76). Complications emerged in 21% (n = 10) versus 29% (n = 23) of vaginal deliveries and 45% (n = 18) versus 53% (n = 40) of cesarean deliveries. The most common delivery complication was excessive bleeding. The follow-up period was 4.9 years in the CONS group and 5.6 years in the OPER group. CONCLUSION(S): Women with rectovaginal endometriosis have comparable and good reproductive prognosis regardless of the treatment method.


Subject(s)
Conservative Treatment/methods , Endometriosis/therapy , Gynecologic Surgical Procedures/methods , Infertility, Female/therapy , Rectum/pathology , Vagina/pathology , Adult , Cohort Studies , Conservative Treatment/trends , Endometriosis/diagnosis , Endometriosis/epidemiology , Female , Follow-Up Studies , Gynecologic Surgical Procedures/trends , Humans , Infertility, Female/diagnosis , Infertility, Female/epidemiology , Pregnancy , Pregnancy Rate/trends , Rectum/surgery , Retrospective Studies , Vagina/surgery
12.
Cancers (Basel) ; 12(12)2020 Dec 19.
Article in English | MEDLINE | ID: mdl-33352722

ABSTRACT

Uterine leiomyomas are benign smooth muscle tumors occurring in 70% of women of reproductive age. The majority of leiomyomas harbor one of three well-established genetic changes: a hotspot mutation in MED12, overexpression of HMGA2, or biallelic loss of FH. The majority of studies have classified leiomyomas by complex and costly methods, such as whole-genome sequencing, or by combining multiple traditional methods, such as immunohistochemistry and Sanger sequencing. The type of specimens and the amount of resources available often determine the choice. A more universal, cost-effective, and scalable method for classifying leiomyomas is needed. The aim of this study was to evaluate whether RNA sequencing can accurately classify formalin-fixed paraffin-embedded (FFPE) leiomyomas. We performed 3'RNA sequencing with 44 leiomyoma and 5 myometrium FFPE samples, revealing that the samples clustered according to the mutation status of MED12, HMGA2, and FH. Furthermore, we confirmed each subtype in a publicly available fresh frozen dataset. These results indicate that a targeted 3'RNA sequencing panel could serve as a cost-effective and robust tool for stratifying both fresh frozen and FFPE leiomyomas. This study also highlights 3'RNA sequencing as a promising method for studying the abundance of unexploited tissue material that is routinely stored in hospital archives.

13.
Int J Gynaecol Obstet ; 151(3): 392-398, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32961589

ABSTRACT

OBJECTIVE: To compare enhanced recovery after surgery (ERAS) and conventional care (CC) protocols on outcomes of laparoscopic hysterectomy (LH) performed in the afternoon. METHODS: A single-center randomized controlled trial was conducted on 120 women undergoing LH who were randomly divided into the intervention group (IG; n=60) and control group (CG; n=60). Women in the IG were treated according to the ERAS protocol and those in the CG according to the CC protocol. The primary outcome was the length of hospitalization. Secondary outcomes were postoperative opioid use, postoperative pain and emesis, complications, operative bleeding, and time. RESULTS: More women discharged during 24 hours in the IG than in the CG (88% vs 55%, P<0.001). The time to actual discharge (19 vs 22 hours, P<0.001) and ready-to-discharge time (15 vs 21 hours, P<0.001) were shorter and the use of oxycodone was lower (0 mg [0-0 vs 2.5 mg [0-10], P<0.001) in the IG than in the CG, respectively. Otherwise, no other significant differences between the groups were observed. The follow-up time was one month. CONCLUSION: The ERAS protocol reduces hospital stay and decreases the use of opioids with no impairment in surgical outcome of LH. ClinicalTrials.gov: NCT03828981.


Subject(s)
Enhanced Recovery After Surgery , Length of Stay , Patient Discharge , Adult , Analgesics, Opioid/therapeutic use , Female , Humans , Hysterectomy/rehabilitation , Laparoscopy/rehabilitation , Middle Aged , Pain, Postoperative/drug therapy , Postoperative Period
14.
J Minim Invasive Gynecol ; 27(4): 868-874, 2020.
Article in English | MEDLINE | ID: mdl-31404711

ABSTRACT

STUDY OBJECTIVE: This study aims to evaluate short- and long-term effects of hysterectomy on health-related quality of life (HRQoL) and compare that with a representative age-standardized sample from the general population. DESIGN: A prospective survey as a part of FINHYST study. SETTING: Four Helsinki area hospitals. PATIENTS: Eight hundred thirty-six women with hysterectomy because of benign indications during 2006. INTERVENTIONS: A change in HRQoL assessed by the 15D instrument at baseline, and after 6 months and 10 years. The HRQoL of women was also compared with that of the age-standardized sample from the general female population. MEASUREMENTS AND MAIN RESULTS: Most hysterectomies were performed laparoscopically (41.8%), followed by vaginal (38.2%) and abdominal (20%) approaches. Indications were classified into 6 subgroups; myoma, abnormal uterine bleeding (AUB), endometriosis, pelvic organ prolapse (POP), adnexal mass, and precancerous lesions. The preoperative mean HRQoL in the patients was lower than that of the general population. In the whole study population, hysterectomy provided the greatest improvement in the dimensions of distress, vitality, discomfort and symptoms, and sexual activity, both short- and long-term. Those operated on for myoma, AUB, endometriosis, and POP showed an improved mean HRQoL after 6 months, whereas after 10 years in those operated on for myoma, AUB, and endometriosis, the HRQoL was still better than at baseline. Women with endometriosis never reached HRQoL of the general population. This is right, but the HRQoL of the general population remained lower than that of all other groups. CONCLUSION: Hysterectomy provided long-term improvement in HRQoL, especially in women with myoma, AUB, and endometriosis.


Subject(s)
Endometriosis , Myoma , Uterine Diseases , Endometriosis/surgery , Female , Follow-Up Studies , Humans , Hysterectomy/methods , Myoma/surgery , Prospective Studies , Quality of Life , Uterine Diseases/surgery
15.
Am J Obstet Gynecol ; 222(6): 588.e1-588.e10, 2020 06.
Article in English | MEDLINE | ID: mdl-31836546

ABSTRACT

BACKGROUND: Patient satisfaction and health-related quality of life are nowadays considered as the most important outcomes of pelvic organ prolapse treatment, and large, prospective clinical studies reporting the patient-reported surgical outcomes are needed. OBJECTIVE: To evaluate the effect of female pelvic organ prolapse surgery on health-related quality of life and patient satisfaction and to determine predictors of outcome. STUDY DESIGN: This prospective nationwide cohort study consisted of 3515 women undergoing surgery for pelvic organ prolapse in 2015. The outcomes were measured by validated health-related quality of life instruments (generic 15D, Pelvic Floor Distress Inventory-20, and Patient Global Impression of Improvement) at 6 months and 2 years postoperatively. The baseline predictors of outcomes were studied with logistic regression analysis. RESULTS: In total, 2528 (72%) women were eligible for analysis at 6 months and 2351 (67%) at 2 years. The mean change in the total 15D score suggested a clinically important improvement at 6 months but not at 2 years. However, an improvement in sexual activity, discomfort and symptoms, and excretion was observed during both follow-up assessments. Altogether, 77% and 72% of the participants reported a clinically significant improvement in Pelvic Floor Distress Inventory-20 at the 6-month and 2-year follow-ups, respectively. A total of 84% were satisfied with the outcome and 90% reported an improvement in comparison with the preoperative state with Patient Global Impression of Improvement-I. The strongest predictive factors for a favorable outcome were advanced apical prolapse (adjusted odds ratio, 2.06; 95% confidence interval, 1.58-2.70) and vaginal bulge (1.90, 1.30-2.80). Smoking was associated with an unfavorable outcome as measured by Patient Global Index of Improvement-I (1.69, 1.02-2.81). CONCLUSION: Pelvic organ prolapse surgery improved health-related quality of life in 7 of 10 patients over a 2-year follow-up period, and patient satisfaction was high. Apical prolapse beyond the hymen and vaginal bulge were the most consistent predictors for improvement. Our results suggest that patients should be encouraged to stop smoking to avoid an unfavorable outcome.


Subject(s)
Fecal Incontinence/physiopathology , Pelvic Organ Prolapse/surgery , Quality of Life , Sexual Dysfunctions, Psychological/physiopathology , Urinary Incontinence/physiopathology , Aged , Cohort Studies , Female , Gynecologic Surgical Procedures , Humans , Logistic Models , Lower Urinary Tract Symptoms/physiopathology , Middle Aged , Minimal Clinically Important Difference , Odds Ratio , Patient Satisfaction , Pelvic Organ Prolapse/epidemiology , Pelvic Organ Prolapse/physiopathology , Pelvic Organ Prolapse/psychology , Prognosis , Plastic Surgery Procedures , Smoking/epidemiology , Surgical Mesh , Treatment Outcome
16.
Surg Endosc ; 34(11): 4874-4882, 2020 11.
Article in English | MEDLINE | ID: mdl-31768724

ABSTRACT

BACKGROUND: Hysterectomy rates are decreasing in many countries, and virtual reality simulators bring new opportunities into residents' surgical education. The objective of this study was to evaluate the effect of training in laparoscopic hysterectomy module with virtual reality simulator on surgical outcomes among residents performing their first laparoscopic hysterectomy. METHODS: This randomized study was carried out at the Department of Obstetrics and Gynecology in Helsinki University Hospital and Hyvinkää Hospital. We recruited twenty residents and randomly signed half of them to train ten times with the laparoscopic hysterectomy module on a virtual reality simulator, while the rest represented the control group. Their first laparoscopic hysterectomy was video recorded and assessed later by using the Objective Structured Assessment of Technical Skills (OSATS) forms and Visual Analog Scale (VAS). The scores and surgical outcomes were compared between the groups. RESULTS: The mean OSATS score for the Global Rating Scale (GRS) was 17.0 (SD 3.1) in the intervention group and 11.2 (SD 2.4) in the control group (p = 0.002). The mean procedure-specific OSATS score was 20.0 (SD 3.3) and 16.0 (SD 2.8) (p = 0.012), and the mean VAS score was 55.0 (SD 14.8) and 29.9 (SD 14.9) (p = 0.001). Operative time was 144 min in the intervention group and 165 min in the control group, but the difference did not reach statistical significance (p = 0.205). There were no differences between the groups in blood loss or direct complications. CONCLUSION: Residents training with a virtual reality simulator prior to the first laparoscopic hysterectomy seem to perform better in the actual live operation. Thus, a virtual reality simulator hysterectomy module could be considered as a part of laparoscopic training curriculum.


Subject(s)
Clinical Competence , Education, Medical, Graduate/methods , Gynecology/education , Hysterectomy/education , Internship and Residency/methods , Laparoscopy/education , Simulation Training/methods , Adult , Curriculum , Female , Humans , Male , Operative Time , Video Recording , Virtual Reality
17.
Acta Obstet Gynecol Scand ; 98(9): 1113-1119, 2019 09.
Article in English | MEDLINE | ID: mdl-30883685

ABSTRACT

INTRODUCTION: The association between endometriosis and breast cancer is unclear. We assessed the risk of breast cancer in women with surgically verified endometriosis, with special focus on the age at cancer diagnosis, time from endometriosis diagnosis and breast cancer histology. MATERIAL AND METHODS: All women with first endometriosis-associated diagnoses occurring concomitantly with relevant surgical codes during 1987-2012 were retrieved from the Finnish Hospital Discharge Register in Finland. Breast cancers diagnosed after the endometriosis diagnosis were identified from the Finnish Cancer Registry. The Finnish female population served as the reference. The endometriosis cohort consisted of 49 933 women (23 210 cases of ovarian, 20 187 peritoneal and 2372 deep infiltrating endometriosis). The outcome measure was the standardized incidence ratio (SIR) with 95% confidence interval (95% CI) of breast cancer calculated for the whole cohort and for the subtypes of endometriosis, stratified by the age at breast cancer diagnosis, histology and time from endometriosis diagnosis. RESULTS: The overall risk of breast cancer (1555 cases) was similar to the reference population (SIR 0.99; 95% CI 0.94-1.03), did not differ in types of endometriosis, and was similar for ductal and lobular breast cancer. However, the SIR of breast cancer was increased in the age group of 20-29 years (SIR 4.44; 95% CI 2.22-7.94) and in the age group of 30-39 years (SIR 1.28; 95% CI 1.03-1.57). The risk of in situ breast cancer (170 cases) was increased in the entire endometriosis cohort (SIR 1.25; 95% CI 1.07-1.44). CONCLUSIONS: The overall risk of breast cancer in women with surgically verified endometriosis was similar to that of general population. However, the risk of breast cancer at young age was increased. Young women with surgically verified endometriosis represent highly symptomatic patients with more frequent surgeries and additional therapies that might also contribute to the risk of breast cancer.


Subject(s)
Breast Neoplasms/epidemiology , Endometriosis/epidemiology , Endometriosis/surgery , Adult , Age Factors , Cohort Studies , Female , Finland/epidemiology , Humans , Incidence , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/epidemiology , Peritoneal Neoplasms/surgery , Registries , Risk Factors
18.
Surg Endosc ; 33(11): 3688-3695, 2019 11.
Article in English | MEDLINE | ID: mdl-30656454

ABSTRACT

BACKGROUND: Gynecological surgery and resident education have changed during recent decades, thus impacting surgical training. Training on simulators must begin before operating on patients. The objective of this study was to evaluate the effect of a simple curriculum on the surgical outcome of the participants' first operative laparoscopy. METHODS: This randomized prospective interventional study was carried out in Helsinki University Hospital and Hyvinkää Hospital. We recruited twenty junior residents in Obstetrics and Gynecology, of which half formed a control group and the rest completed the intervention with a theoretical and a practical part. The participants' first laparoscopic salpingectomy was assessed from video recordings by using Objective Structured Assessment of Technical Skills (OSATS) forms and the Numeric Rating Scale (NRS). The surgical outcome and assessed scores were compared between the groups. RESULTS: We found no differences in operative time, blood loss, or complications, nor in OSATS or NRS scores. In the intervention group, participants with the weakest performances in the simulator, seemed to benefit from the training program more than the participants with the best performances (skill level elevation 29.2-31.6% vs. 21.1-23.3%, respectively). The participants with the best performances in the simulator were scored among the best in the recorded operations as well. CONCLUSION: In this study, we found no difference in the surgical outcome between the groups. However, the participants with low starting levels in the simulator could elevate their skill levels more, though they did not reach the skill level of those with a high starting level. Consequently, we found elevation in skills levels in the simulator tasks, but not in the surgical outcome. Likely, our simple training program with a fixed number of repetitions was insufficient to reach a plateau in the learning curve, and thus the training program in such a curriculum should be proficiency based.


Subject(s)
Clinical Competence , Curriculum , Education, Medical, Graduate/methods , Gynecology/education , Internship and Residency/methods , Laparoscopy/education , Salpingectomy/education , Female , Humans , Learning Curve , Male , Pregnancy , Prospective Studies , Video Recording
19.
Acta Obstet Gynecol Scand ; 98(4): 451-459, 2019 04.
Article in English | MEDLINE | ID: mdl-30578530

ABSTRACT

INTRODUCTION: The management of pelvic organ prolapse (POP) varies significantly between countries. The objective of this study was to describe the methods used for POP surgery in Finland and to identify the factors that affect clinicians' choice to use either a native tissue repair (NTR) or a mesh repair method. MATERIAL AND METHODS: This prospective cohort study included 3535 surgeries covering 83% of all POP operations performed in Finland in 2015. The operative details and patient characteristics, including the Pelvic Floor Distress Inventory (PFDI-20), were compared between three selected surgical methods: NTR, transvaginal mesh (TVM) and abdominal mesh (AM). The predictive factors for the use of mesh augmentation were also studied with logistic regression analysis. RESULTS: The most common method was NTR (n = 2855, 81%), followed by TVM (n = 429, 12%) and AM (n = 251, 7%). Approximately 92% of the patients who underwent primary prolapse surgery underwent NTR, and mesh surgery was used mainly for recurrent prolapse. The strongest predictor of mesh surgery was previous POP surgery for the same vaginal compartment (adjusted odds ratio [OR] = 56, 95% confidence interval [CI] = 38-84 for TVM; adjusted OR = 22, 95% CI = 14-34 for AM). Other predictive factors for mesh surgery were previous hysterectomy, healthcare district, severe bulge symptoms and advanced prolapse. TVM was associated with advanced anterior prolapse and older age. AM surgery was associated with advanced apical and/or posterior compartment prolapse. PFDI-20 scores were the highest in the AM group (108 vs 103 in the TVM group and 98 in the NTR group, P = 0.012), which indicates more bothersome symptoms than in the other groups. CONCLUSIONS: The Finnish practices follow international guidelines that advocate NTR as the principal surgical method for POP. Synthetic mesh augmentation was mainly used in patients with recurrent and advanced prolapse with severe symptoms. The variation in the rates of mesh augmentation for POP surgery in different hospitals implies a lack of sufficient evidence of the most suitable treatment method and indicates a need for national guidelines.


Subject(s)
Gynecologic Surgical Procedures/statistics & numerical data , Pelvic Organ Prolapse/surgery , Reoperation/statistics & numerical data , Surgical Mesh/statistics & numerical data , Aged , Cohort Studies , Female , Finland , Gynecologic Surgical Procedures/methods , Humans , Middle Aged , Pelvic Organ Prolapse/epidemiology , Prospective Studies , Vagina/surgery
20.
Int J Cancer ; 143(11): 2725-2731, 2018 12 01.
Article in English | MEDLINE | ID: mdl-29981163

ABSTRACT

We assessed the association of surgically verified endometriosis and risk of non-gynecological cancers according to the type of endometriosis (i.e., ovarian, peritoneal and deep infiltrating endometriosis). All diagnoses of endometriosis combined with relevant procedural codes were identified from the Finnish Hospital Discharge Register 1987-2012. Non-gynecological cancers diagnosed after the endometriosis diagnosis were obtained from the Finnish Cancer Registry. The cohort of 49,933 women with surgically verified endometriosis and the sub-cohorts of ovarian (n = 23,210), peritoneal (n = 20,187), and deep infiltrating (n = 2,372) endometriosis were analyzed separately. The endometriosis cohort contributed 838,685 person-years of follow-up and the Finnish female population served as the reference cohort. The standardized incidence ratio (SIR) and 95% confidence interval (95%CI) was calculated for each cancer separately. The follow-up ended at emigration, death or on the 31st of December 2014. The non-gynecological cancer risk was not increased among women with endometriosis (SIR 1.03, 95%CI 0.98-1.08). Endometriosis was associated with an increased risk of thyroid cancer in the entire cohort (SIR 1.43, 95%CI 1.23-1.64) and in the sub-cohorts of ovarian and peritoneal endometriosis. We found a decreased risk of mouth and pharynx cancer (SIR 0.60, 95%CI 0.41-0.80), and of pancreatic cancer (SIR 0.76, 95%CI 0.58-0.96). The incidence of basal cell carcinoma was elevated in the entire cohort (SIR 1.18, 95%CI 1.10-1.25) and in the sub-cohorts of ovarian and peritoneal endometriosis. In conclusion, women with surgically verified endometriosis have an altered risk of only few non-gynecological cancers.


Subject(s)
Endometriosis/complications , Neoplasms/etiology , Adolescent , Adult , Child , Cohort Studies , Female , Finland , Humans , Incidence , Middle Aged , Registries , Risk Factors , Young Adult
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