What is the impact of placental tissue damage after laser surgery for twin-twin transfusion syndrome? A secondary analysis of the Solomon trial.

BACKGROUND: The introduction of the Solomon technique for the treatment of twin-twin transfusion syndrome (TTTS) increased placental exposure to laser energy. This study aims to identify the impact of power and energy used in laser treatment on placental tissue and pregnancy outcome. METHODS: Pictures of all dye-injected placentas since the start of the Solomon trial were analyzed. Placental damage was scored using a grading system including visual scar depth and affected proportion of the vascular equator. Parameters analyzed included laser power and total energy, gestational age (GA) at laser, GA at birth, laser-to-delivery interval and preterm prelabor rupture of membranes (PPROM). RESULTS: We included 122 cases in the analysis. More placental damage occurred more often in the Solomon group (42%) compared to the selective group (15%) (p < 0.001). In multivariate analysis, more placental damage was associated with higher laser energy (regression coefficient B 0.002) but not with higher power setting (regression coefficient B -0.442). More damage was associated with earlier GA at birth (regression coefficient B -0.167), higher incidence of PPROM <32 weeks (regression coefficient B 0.003) and a shorter laser-to-delivery interval (regression coefficient B -0.168). CONCLUSIONS: Placental damage is positively associated with more laser energy but negatively associated with higher power setting. More placental damage was associated with a lower GA at birth, shorter laser-to-delivery interval and higher PPROM rate. Whether these results should lead to a change in surgical technique requires more research, both further ex-vivo experiments on human placentas and clinical studies.

Impact of Laser Power and Firing Angle on Coagulation Efficiency in Laser Treatment for Twin-Twin Transfusion Syndrome: An ex vivo Placenta Study.

OBJECTIVE: To assess the impact of laser power and firing angle on coagulation efficiency for closing placental anastomoses in the treatment of twin-twin transfusion syndrome. METHODS: We used an ex vivo blood-perfused human placenta model to compare time to complete coagulation using 30 vs. 50 W of neodymium-doped yttrium aluminum garnet laser power and using a firing angle of 90° vs. 45°. Placentas were perfused with pig blood at 5 mL/min. Differences were analyzed using independent-samples t test, Mann-Whitney U test, or χ2 test as appropriate. RESULTS: Coagulation took less time and energy using 50 W (n = 53) compared to 30 W (n = 52), 11 vs. 22 s (p < 0.001), and 557 vs. 659 J (p = 0.007). Perpendicular coagulation (n = 53) took less time and energy compared to a 45° angle (n = 21), 11 vs. 17 s (p = 0.004), and 557 vs. 871 J (p = 0.004). Bleeding complicated 2 (3%) measurements in the 50-W group, 5 (10%) in the 30-W group, and 3 (14%) in the 45° group. DISCUSSION: In a highly controlled model, a 50-W laser power setting was more energy efficient than 30 W in coagulating a placental vein. A more perpendicular laser firing angle resulted in more efficient coagulation. Furthermore, bleeding due to vessel wall disruption occurred more often with lower power and a more tangential approach.

Twenty-Five Years of Fetoscopic Laser Coagulation in Twin-Twin Transfusion Syndrome: A Systematic Review.

OBJECTIVE: The aim of this study was to assess the perinatal outcome of pregnancies with twin-twin transfusion syndrome (TTTS) treated with laser therapy over the past 25 years, and in relation to different techniques used in this time period. METHODS: A systematic review of studies reporting on perinatal outcome according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines was conducted. The MEDLINE, Embase and Cochrane Library databases were systematically searched. Comparisons were made in respect to time period and laser technique and Quintero stages. RESULTS: In total, 34 studies reporting on 3,868 monochorionic twin pregnancies were included. The mean survival of both twins increased from 35 to 65% (p = 0.012) and for at least one twin from 70 to 88% (p = 0.009) over the past 25 years. Mean gestational age at birth remained stable over the years at 32 weeks gestation. Also, we showed a significantly improved perinatal survival with the evolution of the laser technique from non-selective to selective, selective sequential and the Solomon technique (p = 0.010). DISCUSSION: Since the introduction of laser therapy for TTTS more than two decades ago, perinatal survival improved significantly. Improved outcome is probably associated with several factors, including evolution of the laser technique, learning curve effect, better referral and improved early neonatal care.

Learning curve for fetoscopic laser surgery using cumulative sum analysis.

OBJECTIVE: To identify a learning curve and monitor operator performance for fetoscopic laser surgery for twin-to-twin transfusion syndrome using cumulative sum analysis. DESIGN: Retrospective cohort study. SETTING: National tertiary referral center for invasive fetal therapy. POPULATION: A total of 340 consecutive monochorionic pregnancies with twin-to-twin transfusion syndrome treated with fetoscopic laser coagulation between August 2000 and December 2010. METHODS: A learning curve was generated using learning curve cumulative sum analysis and cumulative sum methodology to assess changes in double survival across the case sequence. Laser surgery was initially performed by two operators, joined by a third and fourth operator after 1 and 2 years, respectively. MAIN OUTCOME MEASURES: Individual operator performance, double perinatal survival at 4 weeks. RESULTS: Overall survival of both twins occurred in 59% (201/340), median gestational age at birth was 32.0 weeks. Cumulative sum graphs showed that level of competence for double survival for the operators was reached after 26, 25, 26, and 35 procedures, respectively. Two operators kept their competence level and continued to improve after completing the initial learning process; two others went out of control at one point in time, according to the cumulative sum boundaries. A difference in learning effect was associated with number of procedures performed annually and previous experience with other ultrasound-guided invasive procedures. CONCLUSIONS: This study shows that all operators reached a level of competence after at least 25 fetoscopic laser procedures and confirms the value of using the cumulative sum method both for learning curve assessment and for ongoing quality control.

Fetal surgery in complicated monoamniotic pregnancies: case series and systematic review of the literature.

OBJECTIVE: This study aimed to analyze perinatal outcome in monoamniotic (MA) pregnancies that underwent antenatal surgical interventions for fetal complications. METHODS: Review of all MA pregnancies treated with antenatal surgical interventions in three fetal treatment centers between 2000 and 2013. Indications were twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, discordant anomalies, or elective reduction. We analyzed associations between indication, type of intervention, perinatal survival, and gestational age (GA) at birth and compared our results with a systematic review of the literature. RESULTS: Fifty-eight MA pregnancies were included. Median GA at treatment was 18.0 weeks (range: 13.1-33.0). Procedures included cord coagulation plus transection (n = 42), cord coagulation without transection (n = 7), laser coagulation of placental anastomoses (n = 7), and one case each with interstitial laser and radiofrequency ablation. Median GA at birth was 34 weeks (range 16.0-41.0), and 75% (53/71) of fetuses intended to survive indeed survived. Literature review included 20 articles, reporting on a total of 45 cases of surgically treated MA pregnancies, showing similar outcome results. CONCLUSION: We present the largest series concerning surgical interventions in complicated MA pregnancies. Despite being rare in experienced hands, a 75% survival is achieved. Collaboration between centers, data sharing, and benchmarking may further improve outcome.

Patient with two secondary somatic-type malignancies in a late recurrence of a testicular non-seminoma: illustration of potential and flaw of the cancer stem cell therapy concept.

Here, we report the case of a patient with a non-seminoma of the left testicle, with an intestinal-type adenocarcinoma and a low grade leiomyosarcoma in a late recurrence 19 years after initial diagnosis. The history of the patient, alive with disease 21 years after initial treatment, illustrates the potential and flaw of the cancer stem cell therapy concept. In addition, it is proposed that residual mature teratoma can be regarded as normalization of cancer due to embryonic patterning, and the development of a secondary somatic-type malignancy as failure of normalization.

Monochorionic triplets complicated by fetofetal transfusion syndrome: a case series and review of the literature.

OBJECTIVE: To compare perinatal outcome in monochorionic (MC) triplets with twin-to-twin transfusion syndrome (TTTS) versus dichorionic (DC) triplets with TTTS. STUDY DESIGN: Retrospective analysis of all triplets with TTTS treated at our center and all cases reported in the literature between 1990 and 2010. Survival and gestational age at birth of MC and DC triplets were compared and stratified by type of intervention. We excluded triplets with one or more fetal deaths <16 weeks' gestation and those with one or more fetuses with congenital anomalies. RESULTS: MC triplets were affected by TTTS in a total of 27 cases, and overall survival was 51% (38/75 fetuses) compared to 105 DC triplets with a survival of 76% (220/291 fetuses) (p < 0.05). Mean gestational age at birth in MC triplets was 28 weeks, compared to 31 weeks in DC triplets (p < 0.05). Perinatal survival of at least one fetus in MC triplet and DC triplet pregnancies was 70% (19/27) and 91% (96/105) (p < 0.05). In DC triplets, survival after laser therapy was significantly improved compared to expectant management, amniodrainage or selective feticide (p < 0.05). CONCLUSION: MC triplets with TTTS are at a considerably higher risk for perinatal mortality and preterm birth than DC triplets. The optimal strategy to manage MC triplets with TTTS, including the role of selective feticide and laser therapy of all anastomoses, is still to be established.