Lung metastases in low-risk gestational trophoblastic neoplasia: a retrospective cohort study.

OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.

Sexual functioning, sexual esteem, genital self-image and psychological and relational functioning in women with Mayer-Rokitansky-Küster-Hauser syndrome: a case-control study.

STUDY QUESTION: Do sexual functioning, sexual esteem, genital self-image and psychological and relational functioning in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome differ from a comparison group of women without the condition? SUMMARY ANSWER: In comparison to controls, women with MRKH with a non-surgically or surgically created neovagina did not differ in psychological and relational functioning but reported lower sexual esteem and more negative genital self-image, intercourse-related pain, clinically relevant sexual distress and sexual dysfunction, with sexual esteem levels strongly associated with sexual distress and sexual dysfunction. WHAT IS KNOWN ALREADY: Studies on sexual functioning measured with standardized questionnaires in women with MRKH syndrome compared with women without the condition have yielded contradictory results. Factors associated with sexual functioning in this patient population have rarely been investigated. STUDY DESIGN, SIZE, DURATION: Between November 2015 and May 2017, 54 women with MRKH syndrome with a neovagina and 79 age-matched healthy women without the condition were enrolled in this case-control study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had to be at least 18-years old and had to live in a steady heterosexual relationship. Women with MRKH syndrome were asked to participate by their (former) gynecologists at three university hospitals and by MRKH peer support group. Controls were recruited via advertisement in local newspapers and social media. Standardized questionnaires were administered to assess sexual functioning, sexual esteem, genital self-image and psychological and relational functioning. MAIN RESULTS AND THE ROLE OF CHANCE: Women with MRKH syndrome with a surgically or non-surgically created neovagina reported significantly more pain during intercourse (P < 0.05, d = 0.5), but did not differ in overall sexual functioning from control women. More women with MRKH syndrome reported clinically relevant sexuality-related distress (P < 0.05, odds ratio (OR): 2.756, 95% CI 1.219-6.232) and suffered a sexual dysfunction (P < 0.05, OR: 2.654, 95% CI: 1.088-6.471) in comparison with controls. MRKH women scored significantly lower on the sexual esteem scale (SES) (P < 0.01, d = 0.5) and the female genital self-image scale (FGSIS) (P < 0.01, d = 0.6) than controls. No significant differences were found between the two groups regarding psychological distress, anxiety and depression, global self-esteem and relational dissatisfaction. Sexual esteem was significantly associated with the presence of clinically relevant sexual distress (ß = 0.455, P = 0.001) and suffering a sexual dysfunction (ß = 0.554, P = 0.001) and explained, respectively, 40% and 28% of the variance. LIMITATIONS, REASONS FOR CAUTION: Given the nature of the study focusing on sexual functioning, a potential selection bias cannot be excluded. It is possible that those women with the most severe sexual and/or psychological disturbances did or did not choose to participate in our study. WIDER IMPLICATIONS OF THE FINDINGS: The study results add new data to the very limited knowledge about psychosexual functioning of women with MRKH syndrome and are of importance for more adequate counseling and treatment of these women. STUDY FUNDING/COMPETING INTEREST(S): The research was financially supported by the Dutch Scientific Society of Sexology (Nederlandse wetenschappelijke Vereniging Voor Seksuologie). The funding was unrestricted, and there was no involvement in the conduct of the research. There are no conflicts of interest to declare.

Management and prognostic factors of epithelioid trophoblastic tumors: Results from the International Society for the Study of Trophoblastic Diseases database.

OBJECTIVE: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT. METHODS: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS). RESULTS: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (n = 23), chemotherapy (n = 6), or a combination of surgery and chemotherapy (n = 25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1 year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (p = 0.012; p = 0.023 respectively). CONCLUSIONS: Advanced-stage disease and an interval of ≥48 months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN.

Trends in incidence for gestational trophoblastic disease over the last 20 years in a population-based study.

BACKGROUND: Gestational trophoblastic disease (GTD) represents a heterogeneous group of disorders. Wide variations in incidence rates are reported worldwide, probably explained by a lack of centralized databases and heterogeneity in case definition. The aim of the present study was to determine the trends in incidence of GTD in the last 20 years with the use of population-based data. PATIENTS AND METHODS: Data on patients with pathologically confirmed diagnosis of GTD between 1994 and 2013 were obtained from PALGA, a nationwide archive containing all pathology reports in the Netherlands. RESULTS: In the 20-year period 6343 cases were registered with GTD, representing an overall incidence rate of 1.67 per 1000 deliveries per year. An initial rise in incidence rate was seen over the first 10 years (0.075 per year, 95% CI 0.040-0.109), followed by a stabilization from 2004 to 2013 (increase per year 0.011, 95% CI -0.017-0.040). Although partial hydatidiform mole (HM) was more common in earlier years, complete and partial HM reached comparable incidence rates of 0.68 and 0.64 per 1000 deliveries respectively from 2009 onwards. In the last decade, unspecified HM diagnosis declined significantly from 0.14 per 1000 deliveries in 2003 to 0.03 per 1000 deliveries (per year -0.011, CI -0.016-0.06), suggesting improved diagnostic analyses. CONCLUSION: After an initial rise in GTD incidence in the Netherlands rates remained steady from 2004 onwards. As pathological confirmation is currently the norm and advanced pathological techniques are now widely available, true steady incidence rates may have been reached.

Fatal cases of gestational trophoblastic neoplasia over four decades in the Netherlands: a retrospective cohort study.

OBJECTIVE: To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management. DESIGN: Retrospective cohort study. SETTING: The Netherlands. POPULATION: Women who died from GTN from 1971 to 2011. METHODS: Records from the Dutch Central Registry for Hydatidiform Moles and the Working Party on Trophoblastic Disease were used to identify fatal cases of GTN. MAIN OUTCOME MEASURES: Disease extent, risk classification, treatment regimens and cause of death. RESULTS: Twenty-six women died from GTN. In five cases GTN developed after a hydatidiform mole and in 19 cases following term pregnancy. Half of the women died between 1971 and 1980, when women were not yet classified as having low-risk or high-risk disease and were therefore not yet treated accordingly. A major decline in the number of deaths was seen after the first decade, with a further decrease from 1981 to 2011. Early death occurred in nine women. In four of these women, death was treatment-related. Women who died more than 4 weeks after the start of treatment mostly died from metastatic tumour (n = 14). CONCLUSIONS: The yearly number of women who died from GTN decreased considerably over the last four decades. Appropriate risk classification is essential to start optimal initial therapy and to prevent therapy resistance. Women with post-term choriocarcinoma represented a large proportion of the dead women and we propose that these women are considered as having high-risk disease.

Total knee arthroplasty improves gait adaptability in osteoarthritis patients; a pilot study.

Background: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients' physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm).Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA.

Limited knee extension during gait after total knee arthroplasty is related to a low Oxford Knee Score.

BACKGROUND: After total knee replacement (TKR) some patients report low self-perceived function, which is clinically measured using patient reported outcome measures (PROMs). However, PROMs, e.g. the Oxford Knee Score (OKS), inherently lack objective parameters of knee function. Biomechanical gait analysis is an objective and reliable measurement to quantitatively assess joint function. Therefore, the aim of this study was to explore the relationship between biomechanical gait parameters and the OKS. METHODS: Gait analyses were recorded in 37 patients at least one year after primary TKR and in 24 healthy controls. Parameters from this analysis were calculated for hip, knee and ankle joint angles and joint moments in the sagittal and frontal plane including initial contact, early, late stance and swing. For the patients these parameters were expressed as its difference to control values at matched walking speed. Linear regression analyses were performed between the parameters from gait analysis and the OKS, with speed as covariate. RESULTS: The difference in knee extension angle at initial contact and late stance between patients and controls was significantly related to the OKS. Per one degree knee extension difference increase, the OKS reduced with 1.0 to 1.6 points. Overall, patients extended their knee less than controls. Neither ankle and hip gait parameters, nor joint moments showed a relation with OKS. CONCLUSIONS: All patients with a submaximal score on the OKS showed limited knee extension during gait, even without a mechanical constraint in knee extension. This could be related to motor control limitations in this patient group.

Matching walking speed of controls affects identification of gait deviations in patients with a total knee replacement.

BACKGROUND: The assessment of functional recovery of patients after a total knee replacement includes the quantification of gait deviations. Comparisons to comfortable gait of healthy controls may incorrectly suggest biomechanical gait deviations, since the usually lower walking speed of patients already causes biomechanical differences. Moreover, taking peak values as parameter might not be sensitive to actual differences. Therefore, this study investigates the effect of matching walking speed and full-waveform versus discrete analyses. METHODS: Gait biomechanics of 25 knee replacement patients were compared to 22 controls in two ways: uncorrected and corrected for walking speed employing principal component analyses, to reconstruct control gait biomechanics at walking speeds matched to the patients. Ankle, knee and hip kinematics and kinetics were compared over the full gait cycle using statistical parametric mapping against using peak values. FINDINGS: All joint kinematics and kinetics gait data were impacted by applying walking speed correction, especially the kinetics of the knee. The lower control walking speeds used for reference generally reduced the magnitude of differences between patient and control gait, however some were enlarged. Full-waveform analysis identified greater deviating gait cycle regions beyond the peaks, but did not make peak value analyses redundant. INTERPRETATION: Matching walking speed of controls affects identification of gait deviations in patients with a total knee replacement, reducing deviations confounded by walking speed and revealing hidden gait deviations related to possible compensations. Full-waveform analysis should be used along peak values for a comprehensive quantification of differences in gait biomechanics.

Effect of walking with a modified gait on activation patterns of the knee spanning muscles in people with medial knee osteoarthritis.

OBJECTIVE: To evaluate muscle activation patterns and co-contraction around the knee in response to walking with modified gait patterns in patients with medial compartment knee-osteoarthritis (KOA). DESIGN: 40 medial KOA patients walked on an instrumented treadmill. Surface EMG activity from seven knee-spanning muscles (gastrocnemius, hamstrings, quadriceps), kinematics, and ground reaction forces were recorded. Patients received real-time visual feedback on target kinematics to modify their gait pattern towards three different gait modifications: Toe-in, Wider steps, Medial Thrust. The individualized feedback aimed to reduce their first peak knee adduction moment (KAM) by ≥10%. Changes in muscle activations and medial/lateral co-contraction index during the loading response phase (10-35% of the gait cycle) were evaluated, for the steps in which ≥10% KAM reduction was achieved. RESULTS: Data from 30 patients were included in the analyses; i.e. all who could successfully reduce their KAM in a sufficient number of steps by ≥10%. When walking with ≥10% KAM reduction, Medial Thrust gait (KAM -31%) showed increased flexor activation (24%), co-contraction (17%) and knee flexion moment (35%). Isolated wider-step gait also reduced the KAM (-26%), but to a smaller extent, but without increasing muscle activation amplitudes and co-contraction. Toe-in gait showed the greatest reduction in the KAM (-35%), but was accompanied by an increased flexor activation of 42% and hence an increased co-contraction index. CONCLUSION: Gait modifications that are most effective in reducing the KAM also yield an increase in co-contraction, thereby compromising at least part of the effects on net knee load.

Haemolytic disease of the newborn because of rare anti-Vel.

Routine screening for maternal immunization in a 36-year-old woman revealed an alloimmunization against the high-incidence Vel antigen during a second pregnancy. Because of the development of immunoglobulin G-type anti-Vel, the infant developed haemolytic disease of the newborn, with severe jaundice and reticulocytosis. Phototherapy was needed to reduce hyperbilirubinaemia.

[Trophoblastic diseases]. / Trofoblastziekten.

Hydatidiform mole is the most frequently-occurring gestational trophoblastic disease (GTD). Patients with GTD have elevated human chorionic gonadotrophin (HCG) produced by the trophoblast. After evacuation of the mole, weekly serum HCG determinations can be used to assess whether the trophoblast is persisting or regressing based on the standardised normal Nijmegen serum HCG regression curve. The serum HCG pattern is used to establish the diagnosis 'persistent trophoblastic disease'. Treatment with monochemotherapy in the form of methotrexate is the treatment of choice. For about 80% of women with a persistent trophoblastic disease following a molar pregnancy this treatment will lead to a complete remission of the disorder. If resistance to methotrexate occurs then a combined therapy is indicated. A recently developed, and as yet unvalidated, normogram for the serum HCG level during methotrexate treatment might in the near future be able to identify patients with methotrexate resistance at an early stage. Hysterectomy or curettage may be indicated as part of therapy in selected patients. The incidence of choriocarcinoma after a live birth is estimated at 1 in every 40,000 full-term pregnancies. These patients have a high risk for resistance to methotrexate (75%). Treatment of these patients with primary combination therapy at a specialised medical centre is then indicated.

Gait retraining using real-time feedback in patients with medial knee osteoarthritis: Feasibility and effects of a six-week gait training program.

BACKGROUND: The knee adduction moment (KAM) is often elevated in medial knee osteoarthritis (KOA). The aim of this study was to evaluate effects on KAM and patient-reported outcomes of a six-week gait training program. METHODS: Twenty-one patients (61 ±â€¯6 years) with KOA participated in a six-week biofeedback training program to encourage increased toe-in (all patients) and increased step-width (five patients). Patients received real-time visual feedback while walking on an instrumented treadmill. We analysed the effect of the gait modification(s) on peak KAM in week six and three and six months post-training. We also evaluated the effect on pain and functional ability. RESULTS: Of 21 patients starting the program, 16 completed it with high attendance (15 and 16 respectively) at the three and six month follow-ups. First peak KAM was significantly reduced by up to 14.0% in week six with non-significant reductions of 8.2% and 5.5% at the follow-ups. Functional ability (assessed using the WOMAC questionnaire) improved significantly after the training (eight point reduction, p = 0.04 in week six and nine point reduction, p = 0.04 at six-month follow-up). There was also a trend towards reduction in WOMAC pain (p = 0.06) at follow-up. CONCLUSIONS: Biofeedback training to encourage gait modifications is feasible and leads to short-term benefits. However, at follow-up, reductions in KAM were less pronounced in some participants suggesting that to influence progression of KOA in the longer term, a permanent regime to reinforce the effects of the training program is needed. Trial number: ISRCTN14687588.

[Anejaculation caused by haemosiderosis: male infertility in hereditary haemochromatosis]. / Zaadloos door ijzerstapeling: mannelijke infertiliteit bij hereditaire hemochromatose.

A couple was investigated for subfertility. Haemochromatosis was suspected when the 36-year-old man had failure of ejaculation, fatigue and limited facial hair growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection therapy, levels of ferritin and transferrin decreased and liver enzymes normalized. However luteinizing hormone and follicle stimulating hormone failed to increase to normal levels. Treatment with gonadotropins was then applied, which corrected ejaculation and semen characteristics. His partner failed to become pregnant with ovulation stimulation and intrauterine inseminations. After two unsuccessful IVF procedures she became pregnant in the third procedure. Haemochromatosis should be considered and iron studies performed if subfertility due to an endocrine disorder is being investigated. Deposition in the pituitary or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the patients with C282Y mutation are homozygous (85-90%), but the majority of the carriers will not develop the disease. Deficiency of hepcidin, an important regulator for the iron metabolism, was suspected in our patient, based on the early onset of his disease and the low serum levels of hepcidin. The age at diagnosis and the start of venesections is critical for reversal of organ damage. Aggressive venesection can restore hypothalamic-pituitary-gonadal function, preventing further organ damage. But with increasing disease progression venesection will not restore azoospermia or the failure to ejaculate.

Clitoral hoodplasty in females with disorders of sex development.

INTRODUCTION: The surgical management of girls with masculinized genitalia is gradually changing towards a more conservative approach. Reports on loss of clitoral sensitivity and related impairment of sexual function in women after feminizing genital surgery in childhood have been pivotal in this evolution. An exposed clitoral glans is occasionally seen at follow-up, and while patients may complain of aesthetics, no clitoral discomfort secondary to glans exposure has been reported. A technique has been developed to reconstruct the clitoral hood and the present study reports the preliminary results. OBJECTIVES: To report the novel technique and preliminary results of clitoral hood reconstruction to cover an exposed glans after previous clitoroplasty in patients with congenital adrenal hyperplasia (CAH). PATIENTS AND METHODS: Six female patients (mean age 13, range 4-21 years) with CAH sought medical help for clitoral concerns after previous reduction clitoroplasty. In two of the six patients, the main complaint was clitoral hypersensitivity or even pain. The clitoral glans was completely exposed in all patients, who were subsequently treated with a bi-laminar V-Y clitoral hoodplasty to create a mobile and natural-looking clitoral hood composed of an inner and outer preputial skin layer. RESULTS: Postoperative covering of the glans was complete in five patients, and partial in one. The two patients with pre-operative pain became asymptomatic; all six patients were pleased with the cosmetic postoperative results. CONCLUSION: Clitoral hoodplasty provides simple, yet effective, relief for women with cosmetic concerns or clitoral discomfort after previous feminizing surgery.

Dextran and adhesions in guinea-pigs.

This prospective, randomized, 'blind' study with guinea-pigs was performed to assess the possible benefit of 6% dextran 70 (molecular weight 70 000) in the prevention of post-operative intra-abdominal adhesions and recurrent adhesions after adhesiolysis. In 50 guinea-pigs lesions for inducing adhesions were applied at the end of the uterine horn. On the right side a strip lesion was made and on the left side an end-to-end anastomosis was performed after section. Before closing the peritoneum 20 ml 6% dextran 70 (N = 25) or saline (N = 25) were introduced into the peritoneal cavity. A second laparotomy 4 weeks later showed no differences in adhesion formation in the animals treated with 6% dextran 70 and saline. In the animals with adhesions adhesiolysis was performed and 6% dextran 70 or saline was left in the peritoneal cavity. Again no beneficial effect of dextran was seen. The end-to-end procedure appeared to be far more suitable for producing adhesions than was the strip lesion.

Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The Netherlands.

OBJECTIVE: To investigate whether a desire for pregnancy changed after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO) treatment for gestational trophoblastic disease and whether the incidence of infertility and adverse pregnancy outcome differed from the general population. DESIGN: A cohort study was performed. Data were collected from hospital records and questionnaires. SETTING: The study was carried out in referral hospitals in The Netherlands. POPULATION: All women registered by the Dutch Working Party on Trophoblastic Disease and treated with EMA/CO were included. METHODS: A questionnaire was sent to all surviving patients treated with EMA/CO from 1986 until 1997. Women who underwent a hysterectomy were excluded from the study. MAIN OUTCOME MEASURE: Pregnancy outcome and pregnancy wish after chemotherapy. RESULTS: Fifty patients were treated with EMA/CO. In 86%, a complete remission was achieved. A questionnaire was sent to 33 patients. Response rate was 82% (27/33). After EMA/CO, 18 of the patients experienced a regular menstrual cycle. Three patients had an amenorrhoea. Fourteen patients had a pregnancy wish. Twelve patients conceived; 21 pregnancies occurred. Sixteen pregnancies were term deliveries. Two pregnancies ended in a miscarriage and two congenitally abnormal children were delivered prematurely. CONCLUSION: After EMA/CO, 86% of women with a pregnancy wish achieved pregnancy. However, women can be so anxious about a new pregnancy that they refrain from it. A causative relation between the two congenitally abnormal children and EMA/CO cannot be determined because of the small sample. The rate of miscarriages is not higher than in the general population. We can reassure patients that pregnancy after EMA/CO has a high probability of success and a favourable outcome. To diminish the fear of getting pregnant in some patients, psychosocial care should be considered in addition to medical care.