Phase 1 Lymfactin (R) Study : Short-term Safety of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Objective: To study the safety and tolerability of Lymfactin (R) treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema. Background: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. Lymfactin (R) is an adenovirus type 5-based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels. Methods: In Phase I, Lymfactin (R) was combined with microvascular lymph node transfer surgery to study the safety and tolerability of Lymfactin (R) and the biodistribution of the viral vector in patients with upper limb lymphedema. Results: Fifteen patients with breast cancer-associated secondary lymphedema of the upper arm were recruited between December 2016 and February 2018. Three patients received a lower dose (1 x 10(10)) and 12 a higher dose (1 x 10(11)) of viral particles, respectively. No dose-limiting toxicities were observed, and the study was completed with the pre-determined maximum dose. Commonly reported adverse events during the 12-month follow-up were common cold, fever, gastroenteritis, pain in the operation area, headache, muscle ache and elevated liver enzymes. Serious adverse events consisted of two erysipelas infections in the lymphedema arm (requiring hospitalization) and one hematoma of the flap donor site. Conclusions: After 12 months' follow-up, results indicate that Lymfactin (R) is well tolerated. The study continues with a 36-months efficacy and 5 years safety follow-up of the patients. The oncological safety aspects of Lymfactin (R) will require a longer follow-up period. (c) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Delay in the initiation of adjuvant chemotherapy in patients with breast cancer with mastectomy with or without immediate breast reconstruction

Background Patients with breast cancer undergoing mastectomy should be offered the option of immediate breast reconstruction (IBR). The aim of this retrospective study was to assess whether there is a delay in the initiation of adjuvant chemotherapy in patients undergoing mastectomy with or without IBR. Method The study included patients aged 70 years or younger with clinically node-negative breast cancer who underwent unilateral mastectomy with IBR (IBR group) or mastectomy alone (no-IBR group) followed by adjuvant chemotherapy at the Helsinki University Hospital between January 2012 to July 2018. Results A total of 645 patients were included; 186 in the IBR group and 459 in the no-IBR group. Sixty-six (35.5 per cent) patients in the IBR group and 102 (22.2 per cent) patients in the no-IBR group received their first chemotherapy cycle later than 6 weeks after surgery (P < 0.001). The respective numbers for later than 8 weeks were 17 (9.1 per cent) and 14 (3.1 per cent) (P = 0.001). Among all 645 patients, postoperative complications were a significant risk factor for a delay in the initiation of chemotherapy. Sixty-seven (39.9 per cent) patients with and 101 (21.2 per cent) patients without complications had a delay in chemotherapy (P < 0.001). The delay in chemotherapy was due to complications in 39 (59.1 per cent) in the IBR group and in 28 (27.5 per cent) in the no-IBR group (P < 0.001). Conclusion Patients undergoing mastectomy alone were more likely to receive adjuvant chemotherapy within 6 weeks after surgery compared with the IBR patients. IBR significantly increased the risk of postoperative complications in comparison with mastectomy alone. The complications, in turn, were a significant risk factor for delay in adjuvant chemotherapy. The aim of this retrospective study was to see whether immediate breast reconstruction (IBR) is linked to a delay in initiation of adjuvant chemotherapy. The study shows that patients undergoing mastectomy alone were more likely to receive adjuvant chemotherapy within the recommended 6 weeks after surgery when compared with IBR patients. IBR significantly increased the risk of postoperative complications and the complications, in turn, were a significant risk factor for delay in adjuvant chemotherapy.Peer reviewe

Use of oral health care services in Finnish adults - results from the cross-sectional Health 2000 and 2011 Surveys

Background: During the 2000s, two major legislative reforms concerning oral health care have been implemented in Finland. One entitled the whole population to subsidized care and the other regulated the timeframes of access to care. Our aim was, in a cross-sectional setting, to assess changes in and determinants of use of oral health care services before the first reform in 2000 and after both reforms in 2011. Methods: The data were part of the nationally representative Health 2000 and 2011 Surveys of adults aged >= 30 years and were gathered by interviews and questionnaires. The outcome was the use of oral health care services during the previous year. Determinants of use among the dentate were grouped according to Andersen's model: predisposing (sex, age group), enabling (education, recall, dental fear, habitual use of services, household income, barriers of access to care), and need (perceived need, self-rated oral health, denture status). Chi square tests and logistic regression analyses were used for statistical evaluation. Results: No major changes or only a minor increase in overall use of oral health care services was seen between the study years. An exception were those belonging to oldest age group who clearly increased their use of services. Also, a significant increase in visiting a public sector dentist was observed, particularly in the age groups that became entitled to subsidized care in 2000. In the private sector, use of services decreased in younger age groups. Determinants for visiting a dentist, regardless of the service sector, remained relatively stable. Being a regular dental visitor was the most significant determinant for having visited a dentist during the previous year. Enabling factors, both organizational and individual, were emphasized. They seemed to enable service utilization particularly in the private sector. Conclusions: Overall changes in the use of oral health care services were relatively small, but in line with the goals set for the reform. Older persons increased use of services in both sectors, implying growing need. Differences between public and private sectors persisted, and recall, costs of care and socioeconomic factors steered choices between the sectors, sustaining inequity in access to care.Peer reviewe

Rintarekonstruktio perustuu moniammatilliseen rintasyövän hoidon kokonaissuunnitteluun ja omakudossiirteiden käyttöön

Vertaisarvioitu.Rintarekonstruktion asema osana kokonaisvaltaista rintasyövän hoitoa on Suomessa vakiintunut. Usein tehdään rintaa säästävä leikkaus, mutta 30-40 % naisista menettää rintansa rintasyöpäleikkauksessa. Rinnan puuttuminen tai merkittävä rintojen kokoero aiheuttavat toiminnallista haittaa, mikä oikeuttaa rekonstruktion. Rintarekonstruktio voidaan tehdä rinnan poiston yhteydessä tai vasta myöhäisvaiheessa. Rintaa voidaan korjata potilaan omalla eli autologisella kudoksella, keinomateriaalein tai menetelmiä yhdistelemällä. Suomessa on käytetty paljon alavatsa- ja selkäkielekettä. Rintaimplantit ja vapaa rasvasiirre ovat itsenäisiä tai täydentäviä tekniikoita. Rintarekonstruktion suunnittelussa potilaan terveydentilan, vartalon muodon ja toiveiden lisäksi ensisijaisen tärkeää on, että syövän hoidon kokonaisuus ei vaarannu. Onkologiset hoidot ovat harvoin este välittömälle rintarekonstruktiolle, kun se suunnitellaan moniammatillisessa tiimissä.Peer reviewe

Phase 1 LymfactinⓇ Study: Short-term Safety of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Objective: To study the safety and tolerability of LymfactinⓇ treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema.Background: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. LymfactinⓇ is an adenovirus type 5–based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels.Methods: In Phase I, LymfactinⓇ was combined with microvascular lymph node transfer surgery to study the safety and tolerability of LymfactinⓇ and the biodistribution of the viral vector in patients with upper limb lymphedema.Results: Fifteen patients with breast cancer–associated secondary lymphedema of the upper arm were recruited between December 2016 and February 2018. Three patients received a lower dose (1 × 1010) and 12 a higher dose (1 × 1011) of viral particles, respectively. No dose-limiting toxicities were observed, and the study was completed with the pre-determined maximum dose. Commonly reported adverse events during the 12-month follow-up were common cold, fever, gastroenteritis, pain in the operation area, headache, muscle ache and elevated liver enzymes. Serious adverse events consisted of two erysipelas infections in the lymphedema arm (requiring hospitalization) and one hematoma of the flap donor site.Conclusions: After 12 months’ follow-up, results indicate that LymfactinⓇ is well tolerated. The study continues with a 36-months efficacy and 5 years safety follow-up of the patients. The oncological safety aspects of LymfactinⓇ will require a longer follow-up period.</p

The Helsinki Face Transplantation : Surgical aspects and 1-year outcome

Background: Since 2005, at least 38 facial transplantations have been performed worldwide. We herein describe the surgical technique and 1-year clinical outcome in Finland's first face transplant case. Methods: A 34-year-old male who had a severe facial deformity following ballistic trauma in 1999 underwent facial transplantation at the Helsinki University Hospital on 8th February 2016. Three-dimensional (3D) technology was used to manufacture donor and recipient patient-specific osteotomy guides and a donor face mask. The facial transplant consisted of a Le Fort II maxilla, central mandible, lower. of the midface muscles, facial and neck skin, oral mucosa, anterior tongue and floor of mouth muscles, facial nerve (three bilateral branches), and bilateral hypoglossal and buccal nerves. Results: At 1-year follow-up, there have thus far been no clinical or histological signs of rejection. The patient has a good aesthetic outcome with symmetrical restoration of the mobile central part of the face, with recovery of pain and light touch sensation to almost the entire facial skin and intraoral mucosa. Electromyography at 1 year has confirmed symmetrical muscle activity in the floor of the mouth and facial musculature, and the patient is able to produce spontaneous smile. Successful social and psychological outcome has also been observed. Post-operative complications requiring intervention included early (nasopalatinal fistula, submandibular sialocele, temporomandibular joint pain and transient type 2 diabetes) and late (intraoral wound and fungal infection, renal impairment and hypertension) complications. Conclusion: At 1 year, we report an overall good functional outcome in Finland's first face transplant. (c) 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Long-term Results of Microvascular Lymph Node Transfer: Correlation of Preoperative Factors and Operation Outcome

Background: Our objective was to analyze whether a correlation could be observed between preoperative factors and microvascular lymph node transfer outcome after long-term follow-up.Methods: We included 67 patients in this retrospective case series. The incidence of cellulitis, the difference of arm circumference, the use of the compression garments both preoperatively and postoperatively, and subjective symptoms, such as pain, were analyzed. Volumetry and lymphoscintigraphy results were also analyzed in a subgroup of patients. We correlated preoperative factors with postoperative results.Results: After 70 +/- 17 months of follow-up, 42% of the patients were able to discontinue the use of compression garments. The subjective pain symptoms were reduced in 75% of the patients. The incidence of cellulitis was reduced from preoperative 0.20 +/- 0.55/y to postoperative 0.02 +/- 0.08/y. As a novel finding, the patients with preoperative cellulitis were more likely to continue the use of the compression garments.Conclusions: The surgery is beneficial to most studied lymphedema patients, although it is not the cure for all patients. The incidence of cellulitis was reduced, and further, the presence of preoperative cellulitis seems to affect the outcome of the operation.</p

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.Peer reviewe

Use of oral health care services in Finnish adults - results from the cross-sectional Health 2000 and 2011 Surveys

Background: During the 2000s, two major legislative reforms concerning oral health care have been implemented in Finland. One entitled the whole population to subsidized care and the other regulated the timeframes of access to care. Our aim was, in a cross-sectional setting, to assess changes in and determinants of use of oral health care services before the first reform in 2000 and after both reforms in 2011.Methods: The data were part of the nationally representative Health 2000 and 2011 Surveys of adults aged >= 30 years and were gathered by interviews and questionnaires. The outcome was the use of oral health care services during the previous year. Determinants of use among the dentate were grouped according to Andersen's model: predisposing (sex, age group), enabling (education, recall, dental fear, habitual use of services, household income, barriers of access to care), and need (perceived need, self-rated oral health, denture status). Chi square tests and logistic regression analyses were used for statistical evaluation.Results: No major changes or only a minor increase in overall use of oral health care services was seen between the study years. An exception were those belonging to oldest age group who clearly increased their use of services. Also, a significant increase in visiting a public sector dentist was observed, particularly in the age groups that became entitled to subsidized care in 2000. In the private sector, use of services decreased in younger age groups. Determinants for visiting a dentist, regardless of the service sector, remained relatively stable. Being a regular dental visitor was the most significant determinant for having visited a dentist during the previous year. Enabling factors, both organizational and individual, were emphasized. They seemed to enable service utilization particularly in the private sector.Conclusions: Overall changes in the use of oral health care services were relatively small, but in line with the goals set for the reform. Older persons increased use of services in both sectors, implying growing need. Differences between public and private sectors persisted, and recall, costs of care and socioeconomic factors steered choices between the sectors, sustaining inequity in access to care