Perinatal outcomes of fetoscopic selective laser photocoagulation for spontaneous twin-anemia polycythemia sequence.

OBJECTIVES: Antenatal management of monochorionic pregnancies complicated by twin anemia polycythemia sequence (TAPS) remains sub-optimally defined. Our objective was to evaluate the safety and efficacy of fetoscopic selective laser photocoagulation with respect to fetal and neonatal survival. METHODS: A case series is reported with patients referred to the Texas Children's Fetal Center for evaluation and management of suspected spontaneous TAPS without concomitant twin-to-twin syndrome from 2014 to 2023. All evaluations were performed by our team and patients with stage II-IV TAPS were offered expectant management, intrauterine transfusion, or laser therapy. Cases of post-laser TAPS were excluded from this study. Pregnancy and neonatal outcomes were obtained from electronic medical records. RESULTS: During a 10-year time period, 18 patients presented to our center for the management of TAPS. Thirteen patients had stage II-IV TAPS (13/18, 72%) and elected to proceed with laser photocoagulation. All procedures were completed, and "solomonization" was performed for 12/13. Normalization of middle cerebral artery Dopplers in both fetuses was noted after all cases. There was one intrauterine fetal death of the 26 viable fetuses after laser treatment, which was complicated by selective growth restriction. Most patients (12/13) were delivered by Cesarean section at a mean gestational age of 29 ± 3 weeks. Subsequently, there was one ex-donor neonatal death in an infant who had prenatal hydrops. Overall, 30-day postnatal survival was 24/26 fetuses (92.3%). CONCLUSIONS: In the setting of spontaneous TAPS, laser therapy is feasible and appears to be an effective approach with overall favorable perinatal outcomes.

Relationship Between the Types and Diameters of Residual Vessels and Secondary TAPS after Fetoscopic Laser Surgery for TTTS.

OBJECTIVE: This study aimed to investigate the relationship between the characteristics and diameters of residual anastomoses and the occurrence of twin anemia-polycythemia sequence (TAPS) in twin-to-twin transfusion syndrome (TTTS) patients with placental vascular injection after fetoscopic laser surgery (FLS). METHODS: A total of 90 cases of pregnant women who underwent FLS owing to TTTS were collected in the university hospital from May 2018 to December 2020. Therein, 40 cases received placental injection and were divided into the TAPS group and non-TAPS group according to the postoperative complications. The number of residual superficial anastomoses was counted and the diameter was measured. RESULTS: Among the placentae of nine patients in the TAPS group, two cases had no superficial anastomoses, and seven cases had 16 superficial anastomoses, including eight arterio-venous (AV) anastomoses, two veno-arterial (VA) anastomoses, three arterio-arterial (AA) anastomoses and three veno-venous (VV) anastomoses. Among the placentae of 31 patients in the non-TAPS group, 19 cases had no superficial anastomoses, and 12 cases had 18 superficial anastomoses, including two AV anastomoses, five VA anastomoses, seven AA anastomoses, and four VV anastomoses; and both the two cases of AV anastomoses were accompanied by AA anastomoses. The number of AV anastomoses in the placentae of the TAPS group was significantly elevated compared with that in the non-TAPS group (p<0.05). While there was no significant difference in the numbers of placentae with superficial anastomoses, the numbers of blood vessels with VA anastomoses, VV anastomoses, and AA anastomoses between the two groups (p>0.05). Through analyzing the diameters of 34 superficial anastomoses in the two groups, it was shown that the diameters of AA anastomoses in the non-TAPS group were significantly larger than those in the TAPS group (Z=1.97, p<0.05). There was no statistical difference in the diameters of AV anastomoses (Z=0.52, p>0.05), VA anastomoses (Z=0.98, p>0.05), and VV anastomoses (Z=0.36, p>0.05). The differences of the birth weight and inter-twin hemoglobin difference were statistically significant (p<0.05). The result indicated that the differences between age, gestational weeks at operation, delivery, and mean operating times were not statistically significant (p>0.05). CONCLUSION: The increase in the number of AV anastomoses could obviously elevate the incidence of TAPS. The probability of TAPS occurrence is reduced following the increased diameters of AA anastomoses, demonstrating that AA anastomosis has a protective effect on TTTS patients.

[A Case of Hepatocellular Carcinoma with Erythrocytosis].

Hepatocellular carcinoma is associated with a relatively high rate of paraneoplastic syndrome, but the frequency of erythrocytosis is low. We report a case of hepatocellular carcinoma with preoperative erythrocytosis and hypererythropoietinemia. The case is a 50-year-old man who has been cured by interferon treatment for hepatitis C 20 years ago(SVR). He visited our hospital with the complaint of right hypochondrial pain, and was diagnosed with hepatocellular carcinoma, which occupied S8/5/7 of the liver, and showed erythrocytosis and high erythropoietin(Epo)as tumor-related symptoms. A right hepatic lobectomy was performed, and the patient was discharged 13 days after the operation. The red blood cell count and Epo were normalized immediately after the operation. One year and 2 months after the operation, multiple lung metastases recurred, and chemotherapy is currently underway. Hepatocellular carcinoma with erythrocytosis and hypererythropoietinemia has been reported to have a poor prognosis, and multimodal treatment and strict surveillance are considered necessary.

Twin anemia polycythemia sequence: Successful laser photocoagulation treatment and placental histopathological findings.

OBJECTIVE: Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic twin pregnancies, which can occur either spontaneously or after laser photocoagulation procedure for twin to twin transfusion syndrome. TAPS is associated with poor perinatal outcomes and clear screening guidelines for this disease are lacking resulting in under-diagnosis of TAPS. CASE REPORT: The purpose of this report is to discuss a case of severe spontaneous TAPS, which was successfully treated with favorable outcome, to describe the placental histopathological findings, and to propose an algorithm for management and follow up of this rare condition. CONCLUSION: Laser photocoagulation of the placental anastomoses, despite technical challenges, can be safely performed in cases of TAPS. Even with prenatal evidence of successful resolution of TAPS, close fetal surveillance is warranted because of the persistence of placental villous immaturity.

Antenatal management and neonatal outcomes of monochorionic twin pregnancies in a tertiary teaching hospital: a 10-year review.

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p<.001, p=.02 and p=.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact StatementWhat is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications.What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC.What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Feline primary erythrocytosis: a multicentre case series of 18 cats.

CASE SERIES SUMMARY: A retrospective multicentre case series of feline primary erythrocytosis (PE) was evaluated. The aim was to gain better understanding of disease presentation and progression to guide management and prognostication. Case records were assessed for evidence of increased packed cell volume (PCV; >48%), sufficient investigation to rule out relative and secondary erythrocytosis, and follow-up data for at least 12 months or until death. Eighteen cats were included in the case series. No significant trends in signalment were noted. Seizures and mentation changes were the most common presenting signs (both n = 10). Median PCV was 70% (median total protein concentration of 76 g/l) with no other consistent haematological changes. Sixteen cats survived to discharge. Phlebotomy was performed initially in 15/16 surviving animals and performed after discharge in 10/16. Hydroxyurea was the most common adjunctive therapy, used in 10/16 cats. Of the 16 patients surviving to discharge, 14 patients were still alive at the conclusion of the study (survival time >17 months post-discharge), with the two non-survivors having lived for 5 years or more after diagnosis. PCV, when stabilised, did not correlate with resolution of clinical signs. RELEVANCE AND NOVEL INFORMATION: In contrast to perceptions, feline PE was generally well managed via a combination of phlebotomy and medical therapy, with evidence of prolonged survival times. The use of hydroxyurea enabled cessation or repeat phlebotomies.

Prenatally Acquired Multiple Limb Ischemia in a Very Low Birth Weight Monochorionic Twin.

Limb ischemia is an extremely rare event occuring in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). The authors describe a case of TTTS and TAPS treated successfully using amnioreduction and laser ablation. However, severe ischemia of both lower extremities in the recipient twin developed after the fetal treatment. This serious complication was diagnosed on MRI in utero and confirmed postnatally. Elective amputation of the affected limbs was performed. The etiology of the disease remains unclear despite profound clinical and histopathological examinations; although the role of thromboembolism in monochorionic pregnancy seems to be most likely, this unique case of multiple limb ischemia with distinct macroscopic findings has not yet been described.

Twin anemia polycythemia sequence: a single center experience and literature review.

Twin anemia polycythemia sequence (TAPS) is defined by significant intertwin hemoglobin discordance without the amniotic fluid discordance that characterizes twin-twin-transfusion syndrome (TTTS) in monochorionic twin pregnancies. TAPS is an uncommon condition which can either occur spontaneously, or following fetoscopic laser ablation for TTTS. This complication is thought to result from chronic transfusion through very small placental anastomoses; however, the pathogenesis of TAPS remains unknown. Consequently, there is no consensus in the management of TAPS. In this article, three cases of TAPS are described and we review the literature on this uncommon pregnancy complication.

Solomon Technique Versus Selective Coagulation for Twin-Twin Transfusion Syndrome.

Monochorionic twin pregnancies can be complicated by twin-to-twin transfusion syndrome (TTTS). The best treatment option for TTTS is fetoscopic laser coagulation of the vascular anastomoses between donor and recipient. After laser therapy, up to 33% residual anastomoses were seen. These residual anastomoses can cause twin anemia polycythemia sequence (TAPS) and recurrent TTTS. In order to reduce the number of residual anastomoses and their complications, a new technique, the Solomon technique, where the whole vascular equator will be coagulated, was introduced. The Solomon technique showed a reduction of recurrent TTS compared to the selective technique. The incidence of recurrent TTTS after the Solomon technique ranged from 0% to 3.9% compared to 5.3-8.5% after the selective technique. The incidence of TAPS after the Solomon technique ranged from 0% to 2.9% compared to 4.2-15.6% after the selective technique. The Solomon technique may improve dual survival rates ranging from 64% to 85% compared to 46-76% for the selective technique. There was no difference reported in procedure-related complications such as intrauterine infection and preterm premature rupture of membranes. The Solomon technique significantly reduced the incidence of TAPS and recurrent TTTS and may improve survival and neonatal outcome, without identifiable adverse outcome or complications; therefore, the Solomon technique is recommended for the treatment of TTTS.

Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence.

OBJECTIVE: The aim of this study is to evaluate the interest in the in utero treatment of twin anemia-polycythemia sequence (TAPS). METHODS: The obstetrical and neonatal data on all cases of TAPS followed up in our institution between 2006 and 2013 were reviewed. Statistical analyses were conducted using Bayesian methods. RESULTS: Twenty cases of TAPS were included. Laser therapy or intrauterine transfusion (IUT) was performed on the donor twin in 9 cases. Eleven cases were included in the 'nontreated' group (managed expectantly or diagnosed at birth). The gestational age at diagnosis was lower in the group with treated TAPS [difference (diff) = -22.20 days (-57.13, 14.28), probability (Pr) (diff >0) = 10.6%]. The rate of preterm premature rupture of membranes was higher in the group with treated TAPS [diff = 22.5% (-14, 57), Pr (diff >0) = 89%], but overall mortality was similar. The interval between diagnosis and delivery was longer [diff = 44.37 days (9.41, 77.90), Pr (diff >0) = 99.2%], the TAPS resolution rate was higher [diff = 49.9% (12, 81), Pr (diff >0) = 99.4%], and the neonatal transfusion rate was lower [diff = -30.5% (-60, 0), Pr (diff >0) = 2.6%] in the treated group. CONCLUSION: In utero treatment for TAPS is associated with a higher resolution rate of TAPS and a longer time between diagnosis and birth, but overall mortality is the same as with expectant management.

Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS).

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. MATERIALS AND METHODS: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. RESULTS: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. DISCUSSION: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.

Treatment of Complicated Spontaneous Twin Anemia-Polycythemia Sequence via Fetoscopic Laser Ablation of the Vascular Communications.

Monochorionic diamniotic twins share a single placenta and have intertwin vascular communications that link the circulatory systems of the twins together. Twin anemia-polycythemia sequence (TAPS) is an atypical form of twin-twin transfusion syndrome (TTTS) caused by net transfer of blood from one fetus to the other and is characterized by large intertwin hemoglobin differences in the absence of oligohydramnios and polyhydramnios. This condition may develop spontaneously (sTAPS) or as a result of residual vascular communications after prior laser surgery. Because of the relatively low prevalence and lack of clinical awareness, the natural history of sTAPS is unclear and the antenatal treatment remains controversial. Case series of sTAPS have described expectant management with timed delivery, intrauterine blood transfusion, and fetoscopic laser treatment. Favorable outcomes have been described in cases of uncomplicated sTAPS that underwent conservative measures. However, we believe that there may be a subgroup of high-risk or complicated sTAPS patients that may benefit from definitive treatment afforded by fetoscopic laser therapy. We describe 3 complicated cases of sTAPS successfully treated with selective laser photocoagulation of communicating vessels. In 2 of the cases, placental pathology identified thrombosed fetal vessels of the polycythemic twin.

An abnormally glycosylated isoform of erythropoietin in hemangioblastoma is associated with polycythemia.

BACKGROUND: Hemangioblastomas express erythropoietin and the patients often present with polycythemia. METHODS: Serum erythropoietin was measured using a commercial immunoassay, a functional erythropoietin assay and iso-electric focusing. RESULTS: Despite the polycythemia, serum erythropoietin remained low, while a functional erythropoietin-assay showed a 4-5 higher activity in serum compared to the immunoassay. Iso-electric focusing of serum erythropoietin indicated overrepresentation of highly sialylated erythropoietin isoforms produced by the tumor. As a result, altered affinity of the monoclonal antibody used in the immunoassay for the hypersialylated isoforms was suggested. CONCLUSION: Analysis of erythropoietin isoforms may be helpful in distinguishing the ectopic erythropoietin isoforms from normally glycosylated erythropoietin.

Neurodevelopmental outcome in twin anemia-polycythemia sequence after laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: To evaluate the long-term neurodevelopmental outcome in children who developed twin anemia-polycythemia sequence (TAPS) after fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). METHODS: Neurological, motor and cognitive development was assessed in a consecutive cohort of TTTS survivors treated with laser surgery between 2004 and 2011 and complicated by post-laser TAPS. Primary outcome was neurodevelopmental impairment, a composite outcome including any of the following: cerebral palsy, bilateral deafness, blindness, severe motor and/or cognitive developmental delay (>2 SD below the mean). A risk analysis on cognitive outcome was performed. RESULTS: During the study period, 33/306 (11%) monochorionic twin pairs developed TAPS after laser surgery for TTTS. Survival was 53/66 (80%). Long-term outcome was assessed in 47/53 (89%) children. The incidence of neurodevelopmental impairment was 4/47 (9%), occurring in one donor (1/20; 5%) and three recipients (3/27; 11%) (P=0.63). Mild-to-moderate cognitive delay, i.e. scores below 85, was detected in 8/47 (17%) children. Risk factors for low cognitive scores were low gestational age at birth (P=0.02) and low birth weight (P<0.01). The lowest cognitive scores were detected in the subgroup of TAPS survivors treated with intrauterine transfusion (median score, 82.5). CONCLUSIONS: Neurodevelopmental impairment and cognitive delay were found in almost one in five children surviving post-laser TAPS. Better treatment and, ideally, prevention of this complication after laser treatment for TTTS is urgently needed.

Laser surgery as a management option for twin anemia-polycythemia sequence.

OBJECTIVE: To evaluate the effectiveness of laser treatment for antenatally detected twin anemia-polycythemia sequence (TAPS) compared with intrauterine transfusion or expectant management. METHODS: All monochorionic twin pregnancies with TAPS managed between 2005 and 2013 in two European fetal therapy centers were evaluated. The outcomes of TAPS cases treated primarily with laser surgery were compared with the outcomes of cases managed expectantly or treated with intrauterine transfusion. RESULTS: In this retrospective study 52 cases of TAPS were detected antenatally and were managed with either laser surgery (n=8; 15%) or intrauterine blood transfusion (n=17; 33%) or expectantly (n=27; 52%). Perinatal survival in the laser group was 94% (15/16) vs 85% (29/34) in the intrauterine-transfusion group and 83% (45/54) in the expectant-management group (P=0.30). The rates of severe neonatal morbidity in liveborn neonates in the laser, intrauterine-transfusion and expectant-management groups were 7% (1/15), 38% (12/32) and 24% (12/50), respectively (P=0.17). There was a significant reduction in respiratory distress syndrome in cases treated by laser. No severe postnatal hematological complications were detected in the laser group compared with 72% (23/32) in the intrauterine-transfusion group and 52% (26/50) in the expectant-management group (P<0.01). Median time between diagnosis and birth was 11 weeks in the laser group compared to 5 weeks after intrauterine transfusion and 8 weeks after expectant management (P<0.01). After injection of colored dye no residual anastomoses were found in the laser group. CONCLUSIONS: Laser surgery for TAPS appears to improve perinatal outcome by prolonging pregnancy and reducing respiratory distress syndrome. Larger, adequately controlled studies are needed to reach firm conclusions on the optimal management of TAPS.