Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

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

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.

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.

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.

Tissue sealants may reduce haematoma and complications in face-lifts: A meta-analysis of comparative studies.

The use of tissue sealants has increased among different surgical specialities. Face-lift and rhytidoplasty may cause several complications such as haematoma, ecchymosis, oedema, seroma, skin necrosis, wound dehiscence and wound infection. However, administration of tissue sealants may prevent the occurrence of some complications. We performed a meta-analysis of studies that compared tissue sealant use with controls to evaluate the outcomes. A systematic literature search was performed. The primary outcome was the incidence of haematoma. Secondary outcomes were wound drainage amount, oedema, ecchymosis, seroma, skin necrosis and hypertrophic scarring. Thirteen studies involving 2434 patients were retrieved and included in the present analysis. A statistically significantly decrease in post-operative haematoma [risk ratio (RR), 0.37; 95% CI, 0.18-0.74; p = 0.005] and wound drainage (MD, -16.90, 95% CI = -25.71, -8.08, p < 0.001) was observed with tissue sealant use. A significant decrease in oedema was detected (RR, 0.30; 95% CI, 0.11-0.85, p = 0.02) but not in ecchymosis, seroma, skin necrosis, and hypertrophic scarring with tissue sealant use. The use of tissue sealants prevents post-operative haematomas and reduces wound drainage. Previous studies have shown a similar trend, but the power of this meta-analysis could verify this perception. LEVEL OF EVIDENCE: III.

Desire for body contouring surgery after bariatric surgery: do body mass index and weight loss matter?

BACKGROUND: There is disparity between the number of postbariatric surgery subjects who desire body contouring and those who receive it due to lack of resources or insurance criteria. OBJECTIVES: The authors evaluate the desire for body contouring after bariatric surgery and its relationship with demographic patient characteristics. METHODS: Three hundred sixty patients who had undergone bariatric surgery procedures >1 year previously completed a questionnaire designed by the surgical team to analyze each patient's desire for body contouring by area (face, upper arm, upper back, chin/neck, chest/breast, waist/abdomen, lower back, rear/buttock), scored from 0 to 3 (do not want, want somewhat, want, want a great deal). Data were compared with patient characteristics, postoperative body mass index (BMI), amount of weight loss, and BMI difference (ΔBMI). RESULTS: Most patients desired body contouring surgery, with high or very high desire for waist/abdomen (62.2%), upper arm (37.6%), chest/breast (28.3%), and rear/buttock (35.6%) contouring. Many patients (36.4%) cited "very high" expectations for how body contouring might change their appearance. Patients >50 years old and >3 years postsurgery had a significantly lower desire. Patients with a ΔBMI >10 and with a weight loss >20 kg showed a significantly stronger overall desire for body contouring compared with other groups. CONCLUSIONS: Most patients desire body contouring surgery after bariatric surgery, and our multivariate analysis showed a significant positive association between female sex, younger age, amount of weight loss, and ΔBMI with desire for body contouring.

Analysis of fat graft metabolic adaptation and vascularization using positron emission tomography-computed tomographic imaging.

BACKGROUND: Fat tissue transfer is commonly used for different soft-tissue defects in surgery. The immediate result of these operations is often good, but the long-term result is unfortunately unpredictable. The authors used an experimental model to evaluate the vascularization, survival, and metabolic changes after free fat transfer and the impact of proangiogenic therapy on these processes. METHODS: Fat was collected from the mouse epididymal region and placed into the subcutaneous tissue of the forehead. Fat grafts were treated with proangiogenic vascular endothelial growth factor (VEGF)-A (n = 9) or the control vector (n = 9). Metabolic activity and fat graft volume were investigated by positron emission tomography-computed tomography at 4 weeks and at 12 weeks. Histologic analysis was performed at 12 weeks. RESULTS: The glucose metabolism (fluorodeoxyglucose uptake) of the transferred epididymal fat was higher than in the epididymal fat before transplantation in both study groups (VEGF-A and control) and resembled that of normal subcutaneous fat. VEGF-A therapy enhanced the survival and capillary density of the transferred fat after surgery. CONCLUSIONS: Transfer of the metabolically inactive (epididymal) fat into a new environment modulated the metabolic activity of the fat grafts to resemble the situation in the recipient site. These novel findings support the clinical use of free fat grafts in various anatomical regions and tissue types. Proangiogenic VEGF-A therapy enhanced the vascularization and survival of the free fat grafts.

Effectiveness of local anaesthetic pain catheters for abdominal donor site analgesia in patients undergoing free lower abdominal flap breast reconstruction: A meta-analysis of comparative studies.

The use of an infusion pain pump with local wound catheters has increased among different surgical specialities. Autologous breast reconstruction with deep inferior epigastric perforator (DIEP) and transverse rectus abdominis myocutaneous (TRAM) flaps may cause severe abdominal donor site morbidity, and infusion devices delivering local anaesthetic are suggested to improve postoperative analgesia. This study performed a meta-analysis comparing pain pump use vs control to evaluate this issue. A systematic literature search was performed. Primary outcome was the amount of opioid use. Secondary outcomes were the amount of antiemetic drugs and the length of hospital stay. Five studies involving 248 patients were retrieved and included in the present analysis. A significantly decreased use of opioids was observed after using pain pump vs control (MD = -15.13, 95% CI = -24.20, -6.06, p = 0.001). Although not statistically significant, the pooled results showed a trend toward reduction of antiemetic medicament use (MD = -0.71, 95% CI = -2.14, 0.72, p = 0.33) and hospital stay time (MD = -0.53, 95% CI = -1.18, 0.11, p = 0.10). The use of local anaesthetic pain catheters for abdominal donor sites in microsurgical breast reconstruction might be associated with a decreased use of narcotics and antiemetic medicaments and shorter hospital stay. Further studies are needed to validate this promising treatment modality.

Physical discomfort due to redundant skin in post-bariatric surgery patients.

Massive weight loss after bariatric surgery leads to excess skin with functional and aesthetic impairments. The aim of this study was to evaluate the prevalence of excess skin after bariatric surgery and identify any relationship with pre- and postoperative characteristics. A total of 360 patients who had undergone bariatric surgery procedures were asked to complete a questionnaire designed by the surgical team at least 1 year after surgery. This questionnaire was planned to estimate any impairment due to redundant skin, which was graded according to a visual analogue scale (VAS, 0--0). Mean (standard deviation, SD) age of 110 males and 250 females was 51.2 (10.8) years. Mean preoperative body mass index (BMI) was 45.7 (6.4) kg m(-2) and mean postoperative BMI at follow-up was 33.6 (6.0) kg m(-2). After a mean follow-up of 56.1 (43.6) months, the mean weight loss was 35.2 (18.8) kg. Most patients (92.8%) reported problems with redundant skin, especially on the abdomen, upper arms and rear/buttocks, which impaired daily physical activity in half of them. Excess skin was associated with female gender (ß=-13.56, 95% confidence interval (CI) -16.81 to -10.32, p<0.0001), weight loss (ß=0.21, 95% CI 0.12-0.29, p<0.0001) and ΔBMI (ß=0.21, 95% CI 0.12-0.29, p<0.0001) at multivariate analysis. Patients with a ΔBMI>20 kg m(-2) showed a significantly surplus skin discomfort compared to ΔBMI≤5 and 5<ΔBMI≤10 (p<0.001). Patients with a weight loss>50 kg showed a significantly redundant skin discomfort compared to weight loss<20 kg (p<0.001). Weight loss after bariatric surgery reduces the medical risks of obesity but psychosocial and functional problems often remain due to the surplus skin. Our data suggest that a ΔBMI≤10 kg m(-2) and weight loss>20 kg, not BMI alone, might be taken into consideration as cut-off values for developing score systems with the intention to apply evidence-based indications for the surgical management of post-bariatric impairments.

Lymphatic vessel function and lymphatic growth factor secretion after microvascular lymph node transfer in lymphedema patients.

BACKGROUND: Recent reports have shown that microvascular lymph node transfer may improve lymphatic drainage in lymphedema patients. Lymphatic anastomoses are expected to form spontaneously in response to lymphatic growth factor [vascular endothelial growth factor C (VEGF-C)] secreted by the transferred lymph nodes. METHODS: We have analyzed the results of 19 lymph node transfer patients operated on 2007-2012. Postoperat ive lymphatic function of the affected arm was evaluated using semiquantitative lymphoscintigraphy (transport index) and limb circumference measurements. To investigate the postoperative VEGF-C secretion, we examined axillary seroma fluid samples after different surgical operations, including lymph node transfer. RESULTS: The transport index was improved postoperatively in 7 of 19 patients. Ten of the 19 patients were able to reduce or even discontinue using compression garments. Arm circumferences were reduced in 12 of 19 patients. Six of the 7 patients with preoperative erysipelas infections have not had infectious episodes postoperatively during 15-67 months follow-up. Neuropathic pain was relieved in 5 of 5 patients. VEGF-C protein was detected in the axillary seroma fluid both after lymph node transfer and normal breast reconstruction. CONCLUSIONS: Reconstructing the lymphatic anatomy of the axilla with a lymph node flap may offer possibilities that other reconstructive options are lacking. However, we will need further reports and comparative studies about the clinical efficacy of this new promising technique. In addition to the transferred lymph nodes, lymphatic growth factor production may also be induced by other factors related to microvascular breast reconstruction.

Donor-site lymphatic function after microvascular lymph node transfer.

BACKGROUND: Lymphedema remains a challenging clinical problem that often lacks curative treatment options. Recent reports have shown that microvascular lymph node transfer from the groin area into axillas of lymphedematous patients may improve lymphatic drainage, but the effect on donor-site lymphatic flow has not been studied. These patients may be more prone to develop lymphedema at donor sites as well; therefore, the authors' aim was to evaluate postoperative donor-site lymphatic function. METHODS: The authors performed lymphatic groin flap transfer to the axilla in 13 lymphedema patients. In 10 patients, the lymph node transfer was performed simultaneously with lower abdominal breast reconstruction. Postoperative lymphatic vessel function of the donor site was evaluated by lymphoscintigraphy and limb circumference measurements. For semiquantitative evaluation of lymphatic drainage, a numerical transport index was used. RESULTS: In six of 10 patients, postoperative lymphoscintigraphy revealed minor changes in lymphatic flow of the donor-site limbs. The transport index was considered slightly abnormal in two of 10 patients. None of the 13 patients had changes in lower limb circumferences during the 8- to 56-month follow-up. CONCLUSIONS: Lymph node transfer can be easily combined with lower abdominal breast reconstruction, and the popularity of this technique is increasing rapidly. Even though none of our patients had developed symptoms of postoperative lymphedema, the results of the first lymphoscintigrams show that it is important to reduce the surgical trauma to the lymphatic flap donor site. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.

Mutations in the ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 cause Hailey-Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis. We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was down-regulated with the small inhibitory RNA (siRNA) method. SiRNA inhibition significantly down-regulated the SPCA1 mRNA, as demonstrated by qPCR, and decreased the SPCA1 protein beyond detectable level, as shown by Western analysis. The expression of selected desmosomal, adherens and tight junction (TJ) proteins was then studied in the SPCA1-deficient and control keratinocytes cultured in low (0.06 mm) or high (1.2 mm) calcium concentration. The mRNA and protein levels of most TJ components were up-regulated in non-treated control keratinocyte cultures upon switch from low to high calcium concentration. In contrast, SPCA1-deficient keratinocytes displayed high levels of TJ proteins claudins 1 and 4 even in low calcium. ZO-1 did not, however, follow similar expression patterns. Protein levels of occludin, beta-catenin, E-cadherin, desmoplakin, desmogleins 1-3, desmocollin 2/desmocollin 3 and plakoglobin did not show marked changes in SPCA1-deficient keratinocytes. Indirect immunofluorescence labelling revealed delayed translocation of desmoplakin and desmoglein 3 in desmosomes and increased intracellular pools of TJ and desmosomal components in SPCA1-inhibited keratinocytes. The results show that SPCA1 regulates the levels of claudins 1 and 4, but does not affect desmosomal protein levels, indicating that TJ proteins are differently regulated. The results also suggest a potential role for claudins in HHD.

Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients.

OBJECTIVE: Postoperative lymphedema after breast cancer surgery is a challenging problem. Recently, a novel microvascular lymph node transfer technique provided a fresh hope for patients with lymphedema. We aimed to combine this new method with the standard breast reconstruction. METHODS: During 2008-2010, we performed free lower abdominal flap breast reconstruction in 87 patients. For all patients with lymphedema symptoms (n = 9), we used a modified lower abdominal reconstruction flap containing lymph nodes and lymphatic vessels surrounding the superficial circumflex vessel pedicle. Operation time, donor site morbidity, and postoperative recovery between the 2 groups (lymphedema breast reconstruction and breast reconstruction) were compared. The effect on the postoperative lymphatic vessel function was examined. RESULTS: The average operation time was 426 minutes in the lymphedema breast reconstruction group and 391 minutes in the breast reconstruction group. The postoperative abdominal seroma formation was increased in patients with lymphedema. Postoperative lymphoscintigraphy demonstrated at least some improvement in lymphatic vessel function in 5 of 6 patients with lymphedema. The upper limb perimeter decreased in 7 of 9 patients. Physiotherapy and compression was no longer needed in 3 of 9 patients. Importantly, we found that human lymph nodes express high levels of endogenous lymphatic vessel growth factors. Transfer of the lymph nodes and the resulting endogenous growth factor expression may thereby induce the regrowth of lymphatic network in the axilla. No edema problems were detected in the lymph node donor area. CONCLUSION: Simultaneous breast and lymphatic reconstruction is an ideal option for patients who suffer from lymphedema after mastectomy and axillary dissection.

Growth factor therapy and autologous lymph node transfer in lymphedema.

BACKGROUND: Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema. METHODS AND RESULTS: The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (ß-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. CONCLUSIONS: These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.

Perfusion in free breast reconstruction flap zones assessed with positron emission tomography.

The aim of this pilot study was to determine the postoperative blood perfusion (BF(PET)) and perfusion heterogeneity (BF(PET) HG) in free microvascular breast reconstruction flap zones with positron emission tomography (PET). Regional BF(PET) and BF(PET) HG of the adipose tissue in medial, central, and lateral parts of 13 free flaps were assessed on the first postoperative morning with PET using oxygen-15-labeled water ([(15)O]H(2)O) in 12 patients undergoing breast reconstruction with a deep inferior epigastric perforator (DIEP) or a transverse rectus abdominis muscle (TRAM) flap. The mean BF(PET) values did not differ between DIEP and TRAM flaps (P = 0.791). The mean BF(PET) values were higher in zone III compared with zone I (P = 0.024). During follow-up, fat necrosis was identified in three patients in the medial part (zone II) of the flap. However, the adipose tissue BF(PET) assessed on the first postoperative day from all zones of the flap using PET with radiowater was normal. The BF(PET) HG was higher in the control side (i.e., in the healthy breast tissue) compared with the flap (P = 0.042). The BF(PET) HG was lower in zone III than in zone I (P = 0.03) and in zone II (P < 0.001). In this pilot study, PET was used for the first time for studying the adipose tissue perfusion in different zones in free flaps in a clinical setup, finding that the mean BF(PET) values did not differ between DIEP and TRAM flaps, and that zone II was sometimes not as well perfused as zone III supporting revisited zone division.

Intraoperative hemodynamic evaluation of the radial and ulnar arteries during free radial forearm flap procedure.

The purpose of this prospective study was to assess the blood flow of the radial and ulnar arteries before and after radial forearm flap raising. Twenty-two patients underwent radial forearm microvascular reconstruction for leg soft tissue defects. Blood flow of the radial, ulnar, and recipient arteries was measured intraoperatively by transit-time and ultrasonic flowmeter. In the in situ radial artery, the mean blood flow was 60.5 +/- 47.7 mL/min before, 6.7 +/- 4.1 mL/min after raising the flap, and 5.8 +/- 2.0 mL/min after end-to-end anastomosis to the recipient artery. In the ulnar artery, the mean blood flow was 60.5 +/- 43.3 mL/min before harvesting the radial forearm flap and significantly increased to 85.7 +/- 57.9 mL/min after radial artery sacrifice. A significant difference was also found between this value and the value of blood flow in the ulnar and radial arteries pooled together ( P < 0.05). The vascular resistance in the ulnar artery decreased significantly after the radial artery flap raising (from 2.7 +/- 3.1 to 1.9 +/- 2.2 peripheral resistance units, P = 0.010). The forearm has a conspicuous arterial vascularization not only through the radial and ulnar arteries but also through the interosseous system. The raising of the radial forearm flap increases blood flow and decreases vascular resistance in the ulnar artery.

The limitations of tissue-oxygen measurement and positron emission tomography as additional methods for postoperative breast reconstruction free-flap monitoring.

Twelve patients who underwent breast reconstruction with a microvascular flap were monitored postoperatively with continuous partial tissue oxygenation (p(ti)O(2)) measurement. The regional blood flow (BF) of the entire flap was evaluated with positron emission tomography (PET) using oxygen-15-labelled water on the first postoperative (POP) morning to achieve data of the perfusion of the entire flap. A re-exploration was carried out if the p(ti)O(2) value remained lower than 15 mmHg for over 30 min. The mean p(ti)O(2) value of the flaps was 52.9+/-5.5 mmHg, whereas the mean BF values were 3.3+/-1.0 ml per 100 g min(-1). One false-positive result was detected by p(ti)O(2) measurement, resulting in an unnecessary re-exploration. Another re-operation suggested by the low p(ti)O(2) results was avoided due to the normal BF results assessed with PET. Totally, three flaps were re-explored. This prospective study suggests that continuous tissue-oxygen measurement with a polarographic needle probe is reliable for monitoring free breast flaps from one part of the flap, but assessing perfusion of the entire flap requires more complex monitoring methods, for example, PET. Clinical examination by experienced personnel remains important in free-breast-flap monitoring. PET could be useful in assessing free-flap perfusion in selected high-risk patients as an alternative to a re-operation when clinical examination and evaluation by other means are unreliable or present controversial results.

Head and neck cutaneous melanoma: a retrospective observational study on 146 patients.

BACKGROUND: Sentinel node biopsy (SNB) is a novel staging technique in cutaneous melanoma, but it is more challenging in the head and neck (H&N) than in the trunk and extremities. The aim of this study was to investigate the utility of SNB in patients with clinical stage I-II H&N cutaneous melanoma, with emphasis on disease outcome. PATIENTS AND METHODS: Twenty five patients with H&N melanoma of >1.0 mm in Breslow depth underwent SNB and were compared to 121 historic H&N melanoma patients, who had either undergone routine prophylactic neck dissection or had been observed without any invasive nodal staging. RESULTS: Sixteen percent of the SNB patients were sentinel-positive and there have been no false-negative cases. In the Kaplan-Meier analysis, there were no significant differences between the study groups in melanoma-specific overall survival. Among the entire cohort, melanoma-specific overall survival rate was 67.1% at 5 years and 61.9% at 10 years. Predictive factors for worsen survival were nodal micrometastases, male sex, scalp location, thick primary lesion and ulceration. DISCUSSION: SNB is a reliable and mini-invasive approach for the nodal staging of H&N cutaneous melanoma. Traditional neck dissection is recommended only for therapeutic purposes in clinically node-positive or sentinel-positive patients.

Targeted treatment for lymphedema and lymphatic metastasis.

The presence of lymphatic vessels has been known for centuries, but the key players regulating the lymphatic vessel growth and function have only been discovered during the recent decade. The lymphatic vasculature is essential for maintenance of normal fluid balance and for the immune response. Hypoplasia or dysfunction of the lymphatic vessels can lead to lymphedema. Currently, lymphedema is treated primarily by physiotherapy, compression garments, and occasionally by surgery, but the means to reconstitute the collecting lymphatic vessels and cure the condition are limited. Specific growth factor therapy has been used in experimental models to regenerate lymphatic capillaries and collecting vessels after surgical damage. Recent results provide a new concept of combining growth factor therapy with lymph node transplantation as a rationale for treating secondary lymphedema. Lymphatic vessels are also involved in lymph node and systemic metastasis of cancer cells; our understanding of mechanisms of lymphatic metastasis has increased remarkably.