Non-progressive mandibular changes in children with Type I and II craniofacial microsomia.

OBJECTIVE: To describe the mandibular growth of craniofacial microsomia (CFM) patients during early childhood to adolescence with attention to symmetry. MATERIALS AND METHODS: Altogether 61 CFM patients were studied at the Cleft Palate and Craniofacial Center, Helsinki University Hospital between 1986 and 2006. In this cohort study, we measured and analysed 293 radiographs (posteroanterior, panoramic and lateral); 165 radiographs of 40 patients met the final inclusion criteria. The vertical height of the ramus in anteroposterior and panoramic radiographs, the length of the mandible in anteroposterior radiographs and the maxillary protrusion and mandibular retrognathia in lateral cephalograms were measured in four different age groups. RESULTS: A statistical difference existed between the groups in the vertical height of the ramus and in the mandibular length. The vertical height of the ramus measured from the panoramic radiograph grew on both sides, and the ratios remained unchanged. In the sagittal dimension, the maxilla and mandible grew forward, but no significant differences emerged between the groups. CONCLUSIONS: Results suggest that mild-type CFM is not progressive in nature. During growth, mandibular asymmetry measured in the horizontal, vertical and sagittal planes did not increase.

Facial asymmetry in children with either unilateral lambdoid craniosynostosis or positional posterior plagiocephaly.

BACKGROUND: In unilateral lambdoid craniosynostosis (ULC), the posteriorly situated lambdoid suture of the cranial vault fuses prematurely. Positional posterior plagiocephaly (PPP) causes flattening of the posterior side of the head, either through external forces or through underlying differences in brain development. Both conditions cause occipital flattening of the head, but the aetiology is different. MATERIALS AND METHODS: Eight ULC children were compared with 16 sex- and age-matched PPP children. 3D computer tomography scans of all 24 children were analysed with Dolphin imaging software. The location and symmetry of the temporomandibular joint (Co), and the symmetry of the maxillary anterior nasal spine (ANS) and the mandibular symphysis (Pgn) were analysed. Furthermore, the mandibular bone (Co-Pgn) length, corpus length, ramus height, positional changes in the external acoustic meatus (PoL) and the distance from the orbital margin to the articular fossa were measured. RESULTS: In all eight ULC children, the Co was anteriorly displaced on the affected side compared with the unaffected side. In all ULC and PPP children, the ANS, which is considered the bony maxillary midpoint, was shifted towards the affected side. In all ULC children, the mandibular bone (Co-Pgn) was shorter on the affected side. The PoL was antero-inferiorly positioned in all ULC children on the affected side compared with the unaffected side. CONCLUSIONS: Our results show that both types of posterior plagiocephaly are associated with an asymmetric position of the Co and asymmetry of the mandible and maxilla. Facial asymmetry was more frequently seen in ULC than PPP children.

Rhinoplasty and Le Fort I Maxillary Osteotomy in Cleft Patients.

INTRODUCTION: Cleft patients often need orthognathic surgery to correct maxillary hypoplasia and rhinoplasty to correct nasal deformity. Rhinoplasty can be performed as a staged procedure after orthognathic surgery or simultaneously with maxillary osteotomy. AIM: The authors evaluated need for and complications of staged and simultaneous rhinoplasties in patients with different cleft types undergoing maxillary osteotomy. PATIENTS AND METHODS: This retrospective study examined 99 (54 females) consecutive nonsyndromic patients with cleft lip/palate [23 bilateral cleft lip and palate (BCLP), 51 unilateral cleft lip and palate (UCLP), and 25 cleft palate (CP)] with a mean age of 17.8 (range: 11.5-45.3) years who had undergone Le Fort I maxillary advancement or bimaxillary osteotomy at the Cleft Palate and Craniofacial Center, Helsinki University Hospital, Finland, between 2002 and 2016. Medical charts were accessed through the hospital's archives and database. RESULTS: Of patients who underwent maxillary osteotomy, 45% (45/99) needed rhinoplasty (14 BCLP, 27 UCLP, and 4 CP). A significant difference (P<0.01) existed in the need for rhinoplasty between different cleft types, those with BCLP and UCLP needing the most operations (60% and 53%). In 20 patients (20%), rhinoplasty was performed simultaneously with maxillary osteotomy, and in 25 patients (25%) in a second operation after osteotomy. The overall complication rate was 14%. No difference existed in complication rate in patients with or without simultaneous rhinoplasty. CONCLUSIONS: Of cleft patients who underwent maxillary osteotomy, 45% needed rhinoplasty. Patients with BCLP and UCLP needed rhinoplasty most often. Staged and simultaneous procedures were almost equally common with similar complication rates.

Diagnosing and Managing Velopharyngeal Insufficiency in Patients With Cleft Palate After Primary Palatoplasty.

Velopharyngeal insufficiency (VPI) after palatoplasty is caused by improper anatomy preventing velopharyngeal closure and manifests as a hypernasal resonance, audible nasal emissions, weak pressure consonants, compensatory articulation, reduced speech loudness, and nostril or facial grimacing. A multidisciplinary team using multimodal instruments (speech analysis, nasoendoscopy, videofluoroscopy, nasometry, and magnetic resonance imaging) to evaluate velopharyngeal function should manage these patients. Careful monitoring of velopharyngeal function by a speech pathologist remains paramount for early identification of VPI and the perceptual assessment should follow a standardized protocol. The greatest methodology problem in CLP studies has been the use of highly variable speech samples making comparison of published results impossible. It is hoped that ongoing international collaborative efforts to standardize procedures for collection and analysis of perceptual data will help this issue. Speech therapy is the mainstay treatment for velopharyngeal mislearning and compensatory articulation, but it cannot improve hypernasality, nasal emissions, or weak pressure consonants, and surgery is the definitive treatment for VPI. Although many surgical methods are available, there is no conclusive data to guide procedure choice. The goal of this review article is to present a review of established diagnostic and management techniques of VPI.

Speech Symptoms of Velopharyngeal Insufficiency and the Incidence of Secondary Speech Surgery in 10-Year-Old Children With Unilateral Cleft Lip and Palate: Comparison of 2 Randomized Surgical Methods for Primary Palatal Surgery.

OBJECTIVE: To compare speech symptoms of velopharyngeal insufficiency (VPI) and incidence of secondary speech surgery in 10-year-old Finnish children with unilateral cleft lip and palate (UCLP) following primary palatal surgery using 2 surgical methods. DESIGN: Single center analysis within the Scandcleft multicenter randomized controlled trial of primary surgery for UCLP. MATERIALS AND METHODS: Patients comprised 79 nonsyndromic 10-year-old children with UCLP. Two randomized surgical methods were used in the primary palatal surgery: soft palate closure at 4 months and hard palate closure at 12 months (Arm A) and closure of both the soft and hard palate at 12 months (Arm C). Speech symptoms of VPI were analyzed from standardized video recordings by 2 experienced speech pathologists. The incidences of surgery for correcting VPI, fistula closure, and speech therapy were evaluated retrospectively from patient records. RESULTS: No differences in speech symptoms of VPI, need for VPI surgery or speech therapy were found between the surgical methods. Of all 79 children, 33% had had VPI surgery and 61% had speech therapy. The number of fistulas was significantly higher in Arm A (25%) than in Arm C (2%). Moderate to severe speech symptoms of VPI (hypernasality, continuous nasal air leakage, weak pressure consonants, and/or compensatory articulation) were found in 11% of the children. CONCLUSION: No differences were present between groups in speech symptoms of VPI or need for VPI surgery or speech therapy between the 2 surgical methods. One third of the children had undergone VPI surgery. Most of the children (89%) had good or relatively good speech.

Outcomes of Primary Furlow Double-Opposing Z-plasty for the Treatment of Symptomatic Submucous Cleft Palate.

BACKGROUND: Submucous cleft palate (SMCP) requires surgical repair if symptomatic. The Furlow double-opposing Z-plasty is the preferred method in Helsinki cleft center. AIMS: To assess the efficacy and complications of Furlow Z-plasty in the treatment of symptomatic SMCP. METHODS: This retrospective study reviewed documentation of 40 consecutive patients with symptomatic SMCP who underwent primary Furlow Z-plasty by 2 high-volume cleft surgeons at a single center between 2008 and 2017. Patients underwent perceptual and instrumental evaluation of velopharyngeal function (VPF) by speech pathologists preoperatively and postoperatively. RESULTS: The median age at Furlow Z-plasty was 4.8 years (SD 2.6, range 3.1-13.6). The overall success rate, including postoperative competent or borderline competent VPF, was 83%, and 10% required secondary surgery for residual velopharyngeal insufficiency. The success rate was 85% in nonsyndromic, and 67% in syndromic patients with no significant difference ( P =0.279). Complications arose in only 2 (5%) patients. No children were found to have obstructive sleep apnea postoperatively. CONCLUSION: Furlow primary Z-plasty is a safe and effective operation for symptomatic SMCP with a success rate of 83% with only 5% rate of complications.

Palatal Re-Repair With Z-Plasty in Treatment of Velopharyngeal Insufficiency of Syndromic and Nonsyndromic Patients With Cleft Palate.

BACKGROUND: Velopharyngeal insufficiency (VPI) often results from palatal shortening or insufficient levator function after cleft palate repair. AIMS: To assess the efficacy of palatal re-repair with Z-plasty in treatment of VPI for patients with isolated cleft palate (ICP). METHODS: This retrospective analysis comprised 130 consecutive patients who had ICP with VPI that required Z-plasty as secondary surgery between 2008 and 2017. Pre- and post-operative evaluation of velopharyngeal function was done perceptually and instrumentally by Nasometer. RESULTS: Median patient age at Z-plasty was 6.8 years (range 3.0-20.1). Of the 130 patients, preoperatively VPI was severe in 73 (56%), mild-to-moderate in 55 (42%), and borderline in 2 (2%). Postoperatively, 105 (81%) of patients achieved adequate (normal or borderline) velopharyngeal competence and 16 (12%) required second operation for residual VPI. The success rate was 84% in nonsyndromic patients, 79% in nonsyndromic Pierre Robin sequence patients, and 58% in syndromic patients. In syndromic children, the speech outcome was significantly worse than in nonsyndromic children (P = 0.014). Complications included wound healing problems in 3 patients (2%), mild infection in 1 patient (1%), postoperative bleeding in 1 (1%), and postoperative fistula in 2 (2%). CONCLUSION: Palatal re-repair with Z-plasty is a safe operation for VPI correction in patients with ICP with a success rate of 81%. In syndromic patients, the procedure did not seem to work as well as in nonsyndromic patients.

Speech of Patients With Unilateral Complete Cleft Lip and Palate: Comparison of Three Different Surgical Protocols for Primary Repair.

BACKGROUND AND AIMS: Between 1997 and 2014, 3 protocols have been used in out cleft unit for primary repair of unilateral cleft lip and palate. During the Scandcleft randomized controlled trial closing the soft palate and lip at 4 months and the hard palate at 12 months (Protocol 1) was compared with closing the entire palate at 12 months (Protocol 2). Protocol 3 comprises closure of the lip and hard palate with a vomer flap at 4 months and the soft palate at 10 months. The purpose of this study was to compare subsequent velopharyngeal competence at age of 3 and 5 years. PATIENTS AND METHODS: The study consisted of 160 non-syndromatic patients with a unilateral cleft lip and palate. Protocol 3 was retrospectively compared with Protocols 1 and 2 within the previously published Scandcleft study. RESULTS: At 3 years of age, normal or borderline competent velopharyngeal function was found in 68% of patients in Protocol 1, 74% of patients in Protocol 2, and 72% of patients in Protocol 3. At 5 years of age, the corresponding figures were 84%, 82%, and 92%. 21% of patients in Protocol 1, 4% in Protocol 2, and 23% in Protocol 3 had palatal reoperations before the age of 5 years. CONCLUSION: No significant differences emerged in velopharyngeal competence at age 3 years between the 3 protocols. Palatal reoperations were performed earlier in patient groups 1 and 3, explaining the difference in the velopharyngeal competence rate at the 5-year time-point.

Palatal Re-Repair With Double-Opposing Z-Plasty in Treatment of Velopharyngeal Insufficiency of Patients With Unilateral Cleft Lip and Palate.

BACKGROUND: Velopharyngeal insufficiency (VPI) is a common problem after cleft palate repair that is often related to palatal shortening and insufficient levator reconstruction. For VPI correction in our cleft center, palatal re-repair with double-opposing Z-plasty is the standard operation. AIMS: To assess the efficacy of double-opposing Z-plasty in treatment of VPI after primary surgery for unilateral cleft lip and palate (UCLP). METHODS: This retrospective analysis comprised 109 consecutive UCLP patients born between 1997 and 2014 with VPI that required re-operation, and were operated on by 2 highvolume cleft surgeons, followed by perceptual and instrumental (Nasometer) evaluation of velopharyngeal competence (VPC). RESULTS: Preoperatively, VPI was severe in 96% (105 of 109) and mild-to-moderate in 4% (4 of 109). Median age at surgery was 5.6 years (range 2.8-21.9). Postoperatively, 84% of patients achieved adequate VPC: 65% (71 of 109) were competent and 19% (21 of 109) borderline competent. Postoperative adequate VPC was 89% (70 of 79) in nonsyndromic Finnish patients, 50% (4 of 8) in syndromic patients, and 82% (18 of 22) in adoption children. Compared to Finnish nonsyndromic patients, patients with syndrome had more residual VPI (P = 0.003), but no statistically significant difference existed for adoption patients (P = 0.251). Complications of the double-opposing Z-plasty included hemorrhage, postoperative mild airway obstruction, and wound-healing problems, each arising in 2 (1.8%) patients. Fourteen (13%) patients needed a second VPI operation. CONCLUSION: Double-opposing Z-plasty seems to be a good and safe treatment option for VPI in patients with previously repaired UCLP with a success rate of 84%.

Combined Surgical Treatment for Chronic Upper Extremity Lymphedema Patients: Simultaneous Lymph Node Transfer and Liposuction.

BACKGROUND: Upper limb lymphedema is a common problem after axillary lymph node dissection. Lymphatic drainage can be improved by microvascular lymph node transfer, whereas liposuction can be used to reduce arm volume and excess of adipose tissue. We present the results of chronic lymphedema patients who have undergone lymph node transfer and liposuction simultaneously in 1 operation and compare the results with patients who have undergone lymph node transfer without liposuction. METHODS: During May 2007 to February 2015, 20 postmastectomy patients and 1 Hodgkin's lymphoma patient presenting with chronic nonpitting lymphedema (age between 37 and 74 years, average 56.7 years) were operated using the combined technique and 27 postmastectomy patients presenting with early-stage lymphedema (age between 31 and 68 years, average age 50.2 years) were operated using only the lymph node transfer. Compression therapy was started immediately after the operation and the patients used compression 24 h/d at least 6 months postoperatively. Changes in clinical parameters (number of erysipelas infections, pain), arm volume, transport indexes calculated form lymphoscintigraphy images, and daily usage of compression garments were compared preoperatively and postoperatively and between groups (combined technique vs lymph node transfer). The study was a retrospective observational study. RESULTS: In the combined technique group, the average arm volume excess decreased postoperatively 87.7%, and in 7 of 10 patients, the edema volume did not increase even without compression. Seventeen of 21 patients were able to reduce the use of compression garment. Lymphoscintigraphy results were improved in 12 of 15 patients and the improvement was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.01). The number of erysipelas infections was decreased in 7 of 10 patients and the decrease was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.02). In the lymph node transfer group, the average excess volume decreased postoperatively 27.5%. Fourteen of 27 patients were able to reduce the use of compression garments. Lymphoscintigraphy results were improved in 8 of 19 patients, and the number of erysipelas infections was decreased in 1 of 3 patients. CONCLUSIONS: Liposuction can safely be performed with lymph node transfer in 1 operation to achieve optimal results in patients with chronic lymphedema. The combined technique provides immediate volume reduction and further regenerative effects on the lymphatic circulation. The significantly greater reduction in lymphoscintigraphy values and erysipelas infections suggests that the combined technique might be better for late-stage lymphedema patients than lymph node transfer alone.

Use of black-bone MRI in the diagnosis of the patients with posterior plagiocephaly.

PURPOSE: Ionising radiation exposure is especially harmful to brain development. The purpose of this study was to evaluate whether black-bone (BB) magnetic resonance imaging (MRI), a non-ionising imaging method, offers an alternative to ionising imaging methods such as computed tomography (CT) in the examination of cranial deformities. METHODS: From 2012 to 2014, a total of 408 children were referred to the Craniofacial Centre at the Helsinki University Hospital for further examination due to flatness of the posterior skull. Fifteen of these patients required further diagnostic imaging. To avoid ionising radiation, we used an MRI protocol that included sequences for evaluation of both brain anatomy and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation algorithm was developed to facilitate the visualisation. Two patients with scaphocephaly were included in the study to confirm the ability to differentiate synostosis with BB-MRI. RESULTS: We obtained informative 3D images using BB-MRI. Seven patients (7/15, 46.7%) had plagiocephaly on the right side and seven on the left side (7/15, 46.7%). One patient (1/15, 6.7%) had symmetric posterior flatness affecting both sides. Neither structural nor signal-intensity alterations of the brain were detected in visual analysis. CONCLUSION: BB-MRI provides an alternative to CT when imaging craniofacial deformities. BB-MRI provides not only high-quality 3D-reconstructed imaging of the bony structures and sutures but also information on brain structure in one imaging session. With further development, this method could replace ionising radiation-based methods in analysing deformities of the skull.

Lymphangiogenesis and Lymphangiogenic Growth Factors.

Lymphedema is a progressive disease caused by damage to the lymphatic network. Recent development in the fields of preclinical growth factor research and lymphedema microsurgery promise new hope for lymphedema patients. In this article, we review the latest results on basic research and highlight the role of specific growth factors in normal lymphatic development and several disease states. Lymph node transfer, a new promising method in reconstructive lymphatic microsurgery, is also dependent on the lymphatic vascular regrowth and lymphangiogenic growth factors. We discuss the scientific basis of lymph node transfer and therapeutic potential of lymphangiogenic growth factors in the treatment of lymphedema.

VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study.

INTRODUCTION: VEGF-C156S, a lymphangiogenesis-specific form of vascular endothelial growth factor C (VEGF-C), has been considered as a promising candidate for the experimental pro-lymphangiogenic treatment, as it lacks potential angiogenic effects. As a precursor to future clinical trials, the therapeutic efficacy and blood vascular side effects of VEGF-C and VEGF-C156S were compared in a large animal model of secondary lymphedema. Combination of lymphatic growth factor treatment and autologous lymph node transfer was used to normalize the lymphatic anatomy after surgical excision of lymphatic tissue. METHODS: Lymph vessels around the inguinal lymph node of female domestic pigs were destroyed in order to impair the normal lymphatic drainage from the hind limb. Local injections of adenoviruses (Ad) encoding VEGF-C or VEGF-C156S were used to enhance the regrowth of the lymphatic vasculature. AdLacZ (ß-galactosidase) and saline injections served as controls. RESULTS: Both VEGF-C and VEGF-C156S induced growth of new lymphatic vessels in the area of excision, although lymphangiogenesis was notably stronger after VEGF-C treatment. Also the transferred lymph nodes were best-preserved in the VEGF-C-treated pigs. Despite the enlargement of blood vessels following the VEGF-C therapy, no signs of sprouting angiogenesis or increased blood vascular permeability in the form of increased wound exudate volumes were observed. CONCLUSIONS: Our results show that VEGF-C provides the preferred alternative for growth factor therapy of lymphedema when compared to VEGF-C156S, due to the superior lymphangiogenic response and minor blood vessel effects. Furthermore, these observations suggest that activation of both VEGFR-2 and VEGFR-3 might be needed for efficient lymphangiogenesis.

Anti-inflammatory effects of flap and lymph node transfer.

BACKGROUND: Transfer of healthy tissue is commonly used in the treatment of complicated wounds and in reconstruction of tissue defects. Recently, microvascular lymph node transfer (LN) has been used to improve the lymphatic function in lymphedema patients. To elucidate the biological effects of flap transfer (with and without lymph nodes), we have studied the postoperative production of proinflammatory, anti-inflammatory, prolymphangiogenic and antilymphangiogenic cytokines, and growth factors (interleukin 1α [IL-1α], IL-1ß, tumor necrosis factor α [TNF-α], IL-10, transforming growth factor ß1 [TGF-ß1], IL-4 and IL-13, and vascular endothelial growth factor C [VEGF-C] and VEGF-D) in postoperative wound exudate samples. METHODS: Axillary wound exudate samples were analyzed from four patient groups: axillary lymph node dissection (ALND), microvascular breast reconstruction (BR), LN, and combined LN and BR (LN-BR). RESULTS: The concentration of proinflammatory cytokines was low in all the flap transfer groups as opposed to the ALND group, which showed an extensive proinflammatory response. The level of anti-inflammatory and antifibrotic cytokine IL-10 was increased in the LN-BR group samples compared with the ALND and BR groups. In the LN and LN-BR groups, the cytokine profile showed an anti-inflammatory response. CONCLUSIONS: Transfer of healthy tissue hinders the proinflammatory response after surgery, which may explain the beneficial effects of flap transfer in various patient groups. In addition, flap transfer with lymph nodes seems to also promote an antifibrotic effect. The clinical effects of LN in lymphedema patients may be mediated by the increased production of prolymphangiogenic growth factor (VEGF-C) and antifibrotic cytokine (IL-10).

Growth factor therapy and lymph node graft for lymphedema.

BACKGROUND: Lymphedema still remains an unsolved problem. Secondary lymphedema often develops after cancer operations or radiation therapy, especially in breast cancer patients. Using a mouse model, we show here that the lymphatic network can be regenerated using lymphatic vascular growth factor therapy in combination with lymph node transfer. MATERIALS AND METHODS: We have compared the therapeutic effects of different vascular endothelial growth factors (VEGF-C, VEGF-D, VEGF-C156S, and VEGF-A), in combination with lymph node transfer in mouse axilla. The lymphangiogenic effects of the growth factor therapy were examined at 3 mo postoperatively. RESULTS: VEGF therapy with VEGF-C and VEGF-D induced growth of new lymphatic vessels in the defect area, and VEGF-C also improved lymphatic vessel function compared with that of controls. VEGF-C156S induced moderate lymphangiogenesis, but the effect remained statistically nonsignificant. Prolymphangiogenic growth factors (VEGF-C, -D, and -C156S) also improved lymph node survival as compared with those of the VEGF-A and control group. VEGF-C, which activates both vascular endothelial growth factor receptor 2 and vascular endothelial growth factor receptor 3, gave the best therapeutic effect in this experimental lymphedema model. CONCLUSIONS: These results support our goal to treat secondary lymphedema by combining lymph node transfer with the growth factor therapy. VEGF-C provides the preferred alternative for growth factor therapy of lymphedema when compared with other VEGF-family growth factors, due to the superior lymphangiogenic response and minor blood vascular effects.

Lambdoid Synostosis Versus Positional Posterior Plagiocephaly, a Comparison of Skull Base and Shape of Calvarium Using Computed Tomography Imaging.

The differential diagnostics between the common positional posterior plagiocephaly and relatively rare lambdoid synostosis is important due to the differences in their treatment plan and clinical management. However, the clinical criteria for the diagnosis of lambdoid synostosis are not clear since there is a considerable overlap in the features of positional posterior plagiocephaly and unilateral lambdoid synostosis. To systematically evaluate the clinical findings in these 2 patient groups, we quantitatively compared the characteristics of endocranial skull base and ectocranial calvarium in 3D computed tomography, in 9 children (mean age 2.9 years) with unilateral lambdoid synostosis and 9 children with positional posterior plagiocephaly. The groups were sex and age matched. Our results show that the skull bases in the lambdoid synostosis are posteriorly shorter and more twisted than in positional posterior plagiocephaly. Anterior twisting was mild in both skull types. Our study confirmed earlier suggested diagnostic feature: prominent ipsilateral mastoidal bossing downward and laterally in all lambdoid skulls. In positional posterior plagiocephaly the bossing was typically not detected. Interestingly, there was a great variation in the position of the ipsilateral ear and external auditory meatus in both patient groups. Thus, neither antero-posterior nor vertical position of ear is a reliable differential diagnostic feature between lambdoid synostosis or positional posterior plagiocephaly.

[Lymphedema]. / Lymfaturvotus.

Chronic swelling due to lymphatic insufficiency (lymphedema) is a common problem after surgical operations, radiation therapy, injuries and infections. Overweight is a new but rapidly increasing component of lymphedema. Treatment of lymphedema is based on compression therapy, lymph therapy and physiotherapy as well as various surgical treatment alternatives. Curative treatment has not been available. Over the last few years new imaging methods, surgical techniques and Finnish basic research have provided new tools for diagnostics and therapy.

Donor-site safety in microvascular lymph node transfer for breast cancer-related lymphedema using reverse lymphatic mapping-A prospective study.

BACKGROUND: Vascularized lymph node transfer (VLNT) is one option among other surgical treatments in the management of breast cancer-related lymphedema (BCRL). The cause of concern regarding VLNT harvested from the groin has been the potential development of secondary lower-extremity lymphedema. This study explored the risks associated with donor-site morbidity following groin VLNT, with or without concomitant breast reconstruction. METHOD: The cohort comprised data from the Lymfactin® Phase I and II trials, conducted from 2016 to 2019, that used perioperative reverse lymphatic mapping. The volume of the lower extremities was measured preoperatively and at 3, 6, and 12 months postoperative, and the adverse events were documented during study visits. RESULTS: Altogether, 51 women with a mean age of 55.5 years were recruited. The mean duration of BCRL was 31.8 months. Among these, 25 (49%) underwent VLNT (VLNT-group) and 26 (51%) underwent VLNT in combination with breast reconstruction (VLNT-BR group). The groups were similar in terms of age, (p = 0.766), BMI (p = 0.316), and duration of BCRL (p = 0.994). Across a period of one year, the volume difference between the lower extremities changed by 22.6 ml (range: -813 to 860.2 ml) (p = 0.067). None of the patients had lower-extremity volume difference exceeding 10% at the 12-month follow-up visit. The most frequent adverse events were postoperative pain (17.7%), wound healing issues (11.8%), and seroma formation (11.8%). Most adverse events (64.6%) were classified as minor. CONCLUSIONS: This prospective study demonstrated that groin VLNT with reverse lymphatic mapping appears safe and does not increase the risk of secondary donor-site lymphedema within one year postoperatively.

Phase II study shows potential benefit of adenoviral vascular endothelial growth factor C (VEGF-C) and lymph node transfer in lymphedema.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication lacking medical treatment. Lymfactin® is an adenovirus type 5-based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C (VEGF-C) expression. Our aim was to evaluate the therapeutic effect of Lymfactin® with vascularized lymph node transfer (VLNT). METHODS: This Phase II, double-blind, placebo-controlled, randomized multicenter study evaluated the efficacy and safety of Lymfactin® in combination with VLNT. The primary endpoints were edema volume, quality of life (LyQoLI), and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous Phase I Lymfactin® study. RESULTS: Thirty-nine patients with BCRL were recruited between June 2018 and December 2019 and randomized to receive either Lymfactin® (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared to the baseline, but without statistical differences between groups at 12 months. Additionally, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin® group compared to the placebo group (p = 0.020). No differences in adverse events were detected between the groups. CONCLUSIONS: This study was one of the few studies to objectively show a positive effect of VLNT in a prospective clinical multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema although failing to show differences between groups in primary outcome measures.

Somatosensory evoked potentials are abnormal with plagiocephaly.

BACKGROUND: Deformational plagiocephaly is usually managed conservatively, as it tends to improve over time and with the use of conservative measures. However, before the year 2017 we operated on patients with severe plagiocephaly and neurological symptoms at the Helsinki Cleft Palate and Craniofacial Center. METHODS: Of the 20 infants with severe deformational plagiocephaly and neurological symptoms referred to us between 2014 and 2016, 10 underwent cranioplasty open reshaping of the posterior cranial vault. The parents of the last 10 patients were given information on the natural history of the condition and the patients were followed up with an outpatient protocol. The aim of this study was to gain information on the brain electrophysiology and recovery of patients after total cranial vault reconstruction by measuring the electroencephalogram (EEG) somatosensory evoked potentials (SEP; median nerve). RESULTS: Of the 10 participants in the operation arm, six had abnormal SEP at least on the affected cerebral hemisphere and all SEPs were recorded as normal when controlled postoperatively. In the follow-up arm, eight out of 10 participants had abnormal SEP at the age of approximately 24 months, and all had normalized SEPs at control visits. CONCLUSION: Our data suggest that cranioplasty open reshaping of the posterior cranial vault did not affect abnormal SEP-EEG recordings. We have abandoned the operations in deformational plagiocephaly patients due to findings suggesting that expanding cranioplasty is not beneficial for brain function in this patient group.