The impact of class I compression stockings on the peripheral microperfusion of the lower limb: A prospective pilot study.

OBJECTIVE: The use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application. METHODS: The total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method. RESULTS: The results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges. CONCLUSION: Mild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization.

The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

AIM: Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. METHOD: The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). RESULTS: Up to 2016 the number of cases increased significantly [annual per cent change (APC) = 6.86, p < 0.001] followed by a decline in the following years (APC = -14.82, p = 0.014; average APC = 2.5, p = 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p < 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. CONCLUSION: Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

[Fluorescence-guided Lymph Vessel Sealing in Systematic Nodal Dissection: a New Surgical Technique to Prevent Lymphorrhea and Lymphocele.] / Fluoreszenzgesteuerte Lymphgefäßversiegelung bei der systematischen Lymphknotendissektion zur Vermeidung von Lymphfisteln und Lymphozelen.

INTRODUCTION: The primary morbidities of inguinal and axillary systematic nodal dissection are lymphatic fistulas and seromas. Intraoperative fluorescence imaging-guided sealing of lymph vessels may prevent these postoperative complications. METHODS: Indocyanine dye was injected intracutaneously into the distal limb before the beginning of the lymphadenectomy. Systematic nodal dissection was performed according to standard protocols. Near-infrared imaging was applied throughout the procedure and real-time fluorescence-guided lymph vessel sealing was performed. RESULTS: Fluorescence-guided lymph vessel sealing was implemented in three patients undergoing axillary systematic lymph node dissection. No adverse events occurred following fluorescence dye injection. All patients could be discharged free of wound complications. CONCLUSION: Fluorescence-guided lymph vessel sealing might be a promising new technique for preventing lymphatic fistulas and lymphocele after systematic lymphadenectomy.

Ureterovesical Anastomosis Complications in Kidney Transplantation: Definition, Risk Factor Analysis, and Prediction by Quantitative Fluorescence Angiography with Indocyanine Green.

Ureteral stenosis and urinary leakage are relevant problems after kidney transplantation. A standardized definition of ureterovesical anastomosis complications after kidney transplantation has not yet been established. This study was designed to demonstrate the predictive power of quantitative indocyanine green (ICG) fluorescence angiography. This bicentric historic cohort study, conducted between November 2015 and December 2019, included 196 kidney transplantations. The associations between quantitative perfusion parameters of near-infrared fluorescence angiography with ICG and the occurrence of different grades of ureterovesical anastomosis complications in the context of donor, recipient, periprocedural, and postoperative characteristics were evaluated. Post-transplant ureterovesical anastomosis complications occurred in 18%. Complications were defined and graded into three categories. They were associated with the time on dialysis (p = 0.0025), the type of donation (p = 0.0404), and the number of postoperative dialysis sessions (p = 0.0173). Median ICG ingress at the proximal ureteral third was 14.00 (5.00-33.00) AU in patients with and 23.50 (4.00-117.00) AU in patients without complications (p = 0.0001, cutoff: 16 AU, sensitivity 70%, specificity 70%, AUC = 0.725, p = 0.0011). The proposed definition and grading of post-transplant ureterovesical anastomosis complications is intended to enable valid comparisons between studies. ICG Fluorescence angiography allows intraoperative quantitative assessment of ureteral microperfusion during kidney transplantation and is able to predict the incidence of ureterovesical anastomosis complications. Registration number: NCT-02775838.

Quantitative Assessment of Intraoperative Laser Fluorescence Angiography With Indocyanine Green Predicts Early Graft Function After Kidney Transplantation.

OBJECTIVE: This study was designed to demonstrate the predictive ability of quantitative indocyanine green (ICG) fluorescence angiography for the short-term postoperative outcome, the occurrence of delayed graft function (DGF), and long-term graft survival. SUMMARY BACKGROUND DATA: DGF is a relevant problem after kidney transplantation; sufficient microperfusion of the allograft is crucial for postoperative organ function. Fluorescence angiography with ICG can serve as an intraoperative quality control of microperfusion. METHODS: This prospective diagnostic study, conducted in 2 German transplantation centers from November 2015 to October 2018, included 128 consecutive kidney transplantations. Intraoperative assessment of the allograft microperfusion was performed by near-infrared fluorescence angiography with ICG; a software was used for quantitative analysis. The associations between perfusion parameters (eg, ICG Ingress) and donor, recipient, peri-procedural, and postoperative characteristics were evaluated. RESULTS: DGF occurred in 23 (24%) kidney recipients from deceased donors. ICG Ingress ( P = 0.0027), donor age ( P = 0.0452), recipient age ( P = 0.0139), and recipient body mass index ( P = 0.0017) were associated with DGF. ICG Ingress correlated significantly with recipient age (r = -0.27662, P = 0.0016), cold and warm ischemia time (r = -0.25204, P = 0.0082; r = -0.19778, P = 0.0283), operating time (r = -0.32208, P = 0.0002), eGFR on postoperative days 1 (r =+0.22674, P = 0.0104) and 7 (r = +0.33189, P = 0.0001). The cutoff value for ICG Ingress was 106.23 AU with sensitivity of 78.3% and specificity of 80.8% ( P < 0.0001) for the prediction of DGF. CONCLUSION: Fluorescence angiography with ICG allows intraoperative quantitative assessment of microperfusion during kidney transplantation. The parameter ICG Ingress reflects recipient and procedure characteristics and is able to predict the incidence of DGF. TRIAL REGISTRATION: Clinicaltrials.gov: NCT-02775838.

Intra- and Extrathoracic Malignant Tracheoesophageal Fistula-A Differentiated Reconstructive Algorithm.

BACKGROUND: Tracheoesophageal fistulae (TEF) after oncologic resections and multimodal treatment are life-threatening and surgically challenging. Radiation and prior procedures hamper wound healing and lead to high complication rates. We present an interdisciplinary algorithm for the treatment of TEF derived from the therapy of consecutive patients. PATIENTS AND METHODS: 18 patients (3 females, 15 males) treated for TEF from January 2015 to July 2017 were included. Two patients were treated palliatively, whereas reconstructions were attempted in 16 cases undergoing 24 procedures. Discontinuity resection and secondary gastric pull-up were performed in two patients. Pedicled reconstructions were pectoralis major (n = 2), sternocleidomastoid muscle (n = 2), latissimus dorsi (n = 1) or intercostal muscle (ICM, n = 7) flaps. Free flaps were anterolateral thigh (ALT, n = 4), combined anterolateral thigh/anteromedial thigh (ALT/AMT, n = 1), jejunum (n = 3) or combined ALT-jejunum flaps (n = 2). RESULTS: Regarding all 18 patients, 11 of 16 reconstructive attempts were primarily successful (61%), whereas long-term success after multiple procedures was possible in 83% (n = 15). The 30-day survival was 89%. Derived from the experience, patients were divided into three subgroups (extrathoracic, cervicothoracic, intrathroracic TEF) and a treatment algorithm was developed. Primary reconstructions for extra- and cervicothoracic TEF were pedicled flaps, whereas free flaps were used in recurrent or persistent cases. Pedicled ICM flaps were mostly used for intrathoracic TEF. CONCLUSION: TEF after multimodal tumor treatment require concerted interdisciplinary efforts for successful reconstruction. We describe a differentiated reconstructive approach including multiple reconstructive techniques from pedicled to chimeric ALT/jejunum flaps. Hereby, successful reconstructions are mostly possible. However, disease and patient-specific morbidity has to be anticipated and requires further interdisciplinary management.

[Postoperative hypocalcemia - the most common complication of endocrine head and neck surgery: acute management]. / Postoperative Hypokalzämie ­ die häufigste Komplikation der endokrinen Chirurgie der Halsregion: Akutes Management.

BACKGROUND: In Germany, 8000 patients are affected by postoperative hypoparathyroidism per year following surgery of the thyroid gland, parathyroidal glands and the larynx. Patients do not only suffer from paresthesia in the acute phase of this complication, but are also adversely affected by the fear of loss of control following episodes of tetany even years after the first episode. OBJECTIVES: Discussion of a diagnostic pathway and presentation of a management pathway for postoperative hypocalcemia. METHODS: Narrative review, analysis and discussion of current literature and expert recommendations. RESULTS: Early determination of calcium and parathyroid hormone allows timely diagnosis and treatment of postoperative hypoparathyroidism. Active vitamin D is pivotal for the resorption of calcium. Only the combined treatment with active vitamin D and calcium can mitigate or prevent the postoperative drop of calcium levels. CONCLUSIONS: A standard operating procedure (SOP) for postoperative hypoparathyroidism should be implemented in every surgical department. An SOP for diagnosis and treatment of postoperative hypoparathyroidism is proposed for institutional individualization and implementation.

Involvement of platelet-derived VWF in metastatic growth of melanoma in the brain.

BACKGROUND: The prognosis of patients with brain metastases (BM) is poor despite advances in our understanding of the underlying pathophysiology. The high incidence of thrombotic complications defines tumor progression and the high mortality rate. We, therefore, postulated that von Willebrand factor (VWF) promotes BM via its ability to induce platelet aggregation and thrombosis. METHODS: We measured the abundance of VWF in the blood and intravascular platelet aggregates of patients with BM, and determined the specific contribution of endothelial and platelet-derived VWF using in vitro models and microfluidics. The relevance for the brain metastatic cascade in vivo was demonstrated in ret transgenic mice, which spontaneously develop BM, and by the intracardiac injection of melanoma cells. RESULTS: Higher levels of plasma VWF in patients with BM were associated with enhanced intraluminal VWF fiber formation and platelet aggregation in the metastatic tissue and peritumoral regions. Platelet activation triggered the formation of VWF multimers, promoting platelet aggregation and activation, in turn enhancing tumor invasiveness. The absence of VWF in platelets, or the blocking of platelet activation, abolished platelet aggregation, and reduced tumor cell transmigration. Anticoagulation and platelet inhibition consistently reduced the number of BM in preclinical animal models. CONCLUSIONS: Our data indicate that platelet-derived VWF is involved in cerebral clot formation and in metastatic growth of melanoma in the brain. Targeting platelet activation with low-molecular-weight heparins represents a promising therapeutic approach to prevent melanoma BM.

Definition and severity grading of postoperative lymphatic leakage following inguinal lymph node dissection.

PURPOSE: Lymphatic complications occur frequently after radical inguinal lymph node dissection (RILND). The incidence of lymphatic leakage varies considerably among different studies due to the lack of a consistent definition. The aim of the present study is to propose a standardized definition and grading of different types of lymphatic leakage after groin dissection. METHODS: A bicentric retrospective analysis of 82 patients who had undergone RILND was conducted. A classification of postoperative lymphatic leakage was developed on the basis of the daily drainage output, any necessary postoperative interventions and reoperations, and any delay in adjuvant treatment. RESULTS: In the majority of cases, RILND was performed in patients with inguinal metastases of malignant melanoma (n = 71). Reinterventions were necessary in 15% of the patients and reoperations in 32%. A new classification of postoperative lymphatic leakage was developed. According to this definition, grade A lymphatic leakage (continued secretion of lymphatic fluid from the surgical drains without further complications) occurred in 13% of the patients, grade B lymphatic leakage (persistent drainage for more than 10 postoperative days or the occurrence of a seroma after the initial removal of the drain that requires an intervention) in 28%, and grade C lymphatic leakage (causing a reoperation or a subsequent conflict with medical measures) in 33%. The drainage volume on the second postoperative day was a suitable predictor for a complicated lymphatic leakage (grades B and C) with a cutoff of 110 ml. CONCLUSION: The proposed definition is clinically relevant, is easy to employ, and may serve as the definition of a standardized endpoint for the assessment of lymphatic morbidity after RILND in future studies.

Application of Fluorescent Dyes in Visceral Surgery: State of the Art and Future Perspectives.

BACKGROUND: Through the improvement and implementation of advanced intraoperative imaging, the indications for intraoperative fluorescence have spread to various fields of visceral surgery. Indocyanine green (ICG)-based fluorescence angiography and the imaging systems using this certain dye are currently the cornerstone of intraoperative, fluorescence-based medical imaging. SUMMARY: The article focuses on principles and approaches of intraoperative fluorescence in general surgery. The current clinical practice of intraoperative fluorescence and its evidence are described. Emerging new fields of application are put in a perspective. Furthermore, the technique and possible pit-falls in the performance of intraoperative ICG fluorescence angiography are described in this review article. KEY MESSAGES: Overall growing evidence suggests that intraoperative fluorescence imaging delivers valuable additional information to the surgeon, which might help to perform surgery more exactly and reduce perioperative complications. Perfusion assessment can be a helpful tool when performing critical anastomoses. There is evidence from prospective and randomized trials for the benefit of intraoperative ICG fluorescence angiography during esophageal reconstruction, colorectal surgery, and surgery for mesenteric ischemia. Most studies suggest the administration of 2.5-10 mg of ICG. Standardized settings and documentation are essential. The benefit of ICG fluorescence imaging for gastrointestinal sentinel node detection and detection of liver tumors and colorectal metastases of the liver cannot clearly be estimated duo to the small number of prospective studies. Critical points in the use of intraoperative fluorescence imaging remain the low standardization and reproducibility of the results and the associated difficulty in comparing the results of the existing trials. Furthermore, little is known about the influence of hemodynamic parameters on the quantitative assessment of ICG fluorescence during surgery.

Neoadjuvant Pazopanib Treatment in High-Risk Soft Tissue Sarcoma: A Quantitative Dynamic 18F-FDG PET/CT Study of the German Interdisciplinary Sarcoma Group.

The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we evaluate the potential role of kinetic analysis of fludeoxyglucose F-18 (18F-FDG) data derived from the application of dynamic positron emission tomography/computed tomography (PET/CT) in response assessment to pazopanib of STS patients scheduled for surgical resection. Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on standardized uptake value (SUV) calculations, and quantitative analysis of the dynamic 18F-FDG PET data, based on two-tissue compartment modeling. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded in 14/16 patients. Time to tumor relapse/progression was also calculated. In the follow-up, 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient died. Median histopathological regression was 20% (mean 26%, range 5-70%). The studied population was dichotomized using a histopathological regression grade of 20% as cut-off. Based on this threshold, 10/14 patients (71%) showed partial remission (PR), while stable disease (SD) was seen in the rest 4 evaluable patients (29%). Semi-quantitative evaluation showed no statistically significant change in the widely used PET parameters, SUVaverage and SUVmax. On the other hand, 18F-FDG kinetic analysis revealed a significant decrease in the perfusion-related parameter K1, which reflects the carrier-mediated transport of 18F-FDG from plasma to tumor. This decrease can be considered as a marker in response to pazopanib in STS and could be due to the anti-angiogenic effect of the therapeutic agent.

Preoperative Pazopanib in High-Risk Soft Tissue Sarcoma: Phase II Window-of Opportunity Study of the German Interdisciplinary Sarcoma Group (NOPASS/GISG-04).

BACKGROUND: Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS. METHODS: This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naïve, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day 'window of opportunity'). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUVmean] in post- vs. pretreatment fluorodeoxyglucose-positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors. RESULTS: Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n = 15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval < 0.01-0.29). Mean change in SUVmean of post- versus pretreatment PET was a 6% decrease (range 65% decrease to 34% increase); 7/21 (33.3%) patients had 12 grade 3/4 toxicities, and 19/21 (95.2%) patients were resected (all R0). One (4.8%) patient suffered a grade 4 postoperative complication (anastomotic leakage). Circulating endothelial progenitor cells, soluble vascular endothelial growth factor, and angiopoietin-2 concentrations showed no relevant changes during treatment. CONCLUSIONS: Although this study showed that preoperative pazopanib is not effective for unselected high-risk STS patients, relevant treatment effects were observed in a single patient. Future research needs to better define subgroups potentially benefiting from preoperative pazopanib treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT01543802.

Tissue sealants for the prevention of lymphoceles after radical inguinal lymph node dissection in patients with melanoma: A systematic review and individual patient data meta-analysis.

BACKGROUND AND OBJECTIVES: Postoperative lymphoceles and further wound complications occur frequently after radical inguinal lymph node dissection (ILND). In various studies, tissue sealants have shown to reduce the incidence of postoperative morbidity. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness of tissue sealants in reducing the incidence of postoperative lymphoceles following ILND in patients with melanoma was conducted. Individual patient data was requested to pool the data for meta-analysis appropriately. RESULTS: Thousand seven hundred twenty-nine manuscripts were screened for eligibility. Six RCTs published between 1986 and 2012 were identified including 194 patients for ILND. Only four RCTs were included in the meta-analysis. No study properly defined the term "lymphocele." Tissue sealants failed to influence the duration of drain placement (mean difference [MD] = -3.05 days; z = 1.18; P = 0.24), total drainage volume (MD = 598.39 mL; z = 1.49; P = 0.14), the incidence of postoperative seroma, wound infection and skin necrosis. CONCLUSIONS: No improvement was identified with the use of tissue sealants, however, a valid comparison of the results of included trials was difficult owing to the lack of a definition of the term "lymphocele." Other surgical techniques and trials using validated endpoint definitions are required to reevaluate these findings.

Quantitative assessment of microperfusion by indocyanine green angiography in kidney transplantation resembles chronic morphological changes in kidney specimens.

OBJECTIVE: ICG fluorescence angiography enables a quantitative real-time perfusion assessment in kidney transplantation. The results of intraoperative microperfusion of the kidney allograft were compared to the renal chronicity score in pre-transplantation kidney biopsy specimens. The intrarenal resistance index was calculated by duplex sonography as a method of reference. METHODS: Seventy-seven patients with end-stage renal disease undergoing kidney transplantation were prospectively included in two centers. Correlation analysis of chronic changes in kidney biopsy specimens and the IN of ICG fluorescence signal were investigated. RESULTS: The results yielded a significantly negative correlation for the renal chronicity (r = -0.294, P = 0.017) as well as the intestinal fibrosis and tubular atrophy score (r = -0.328, P = 0.007). There was a significant inverse relationship between the IN and the mean RI values of the upper pole of the kidney allograft. CONCLUSIONS: In summary, fluorescence angiography reflects preexisting morphological changes of the renal cortex. ICG angiography may serve as an alternative method for the assessment of microperfusion of the kidney allograft.

Extensive intraperitoneal lavage to eliminate intraperitoneal tumor cells in gastrectomy with D2 lymphadenectomy for gastric cancer.

INTRODUCTION:: Survival in gastric cancer is often limited by peritoneal carcinomatosis, which supposedly develops from serosal tumor infiltration or tumor cell spread during gastrectomy with lymphadenectomy. To eliminate peritoneal tumor cells, extensive intraperitoneal lavage (EIPL) has been suggested. Impressive results have been achieved in Japanese trials. In this trial, we assessed EIPL in Western patients. METHODS:: This prospective trial included patients with non-metastatic gastric adenocarcinoma undergoing gastrectomy with D2 lymphadenectomy. Peritoneal fluid samples at laparotomy, after lymphadenectomy, and after EIPL were analyzed for tumor cells using cytology and EpCAM antibodies. The primary endpoint was peritoneal conversion rate (PCR; proportion of patients in whom EIPL eliminated tumor cells after lymphadenectomy). Secondary endpoints were peritoneal release rate (PRR; proportion of patients with peritoneal tumor cells after gastrectomy/lymphadenectomy among all patients without cells before gastrectomy/lymphadenectomy) and prevalence of peritoneal tumor cells before resection. EIPL was considered ineffective if PCR ⩽ 0.2 and warranted further exploration if PCR ⩾ 0.5. Clinicaltrials.gov identifier is NCT01476553. RESULTS:: The trial was stopped early because tumor cells after gastrectomy/lymphadenectomy were detected in only 3/27 (11.1%) patients. In none of these did EIPL eliminate tumor cells (PCR 0, 95% confidence interval [CI] 0%-12.5%). In 8/27 (29.6%) patients, tumor cells were detected after EIPL. PRR was 11.1% (95% CI 2.4%-29.2%). There were no perioperative complications higher than Clavien-Dindo grade 3a. CONCLUSIONS:: In Western patients, free peritoneal tumor cells after gastrectomy with D2 lymphadenectomy for gastric cancer were detected only sporadically. Although based on few cases, the findings suggest that EIPL spreads tumor cells into the peritoneal cavity, thus being potentially harmful. Therefore, EIPL cannot be generally recommended.

[Intraoperative Indocyanine Green Fluorescence to Assure Vital Parathyroids in Thyroid Resections]. / Intraoperative Indocyaningrün-Fluoreszenzbildgebung zur Sicherung vitaler Nebenschilddrüsen bei Schilddrüsenresektionen.

INTRODUCTION: Total thyreoidectomy is associated with high rates of temporary or permanent hypoparathyroidism. During surgery, ICG fluorescence angiography can be used to detect and preserve well vascularised parathyroid glands; this technique has been recently introduced in retrospective and prospective trials as an intraoperative technical support to avoid postoperative hypoparathyroidism. MATERIALS UND METHODS: 27 patients undergoing total thyreoidectomy were prospectively enrolled in our study. The vascularisation of the parathyroid glands was analysed intraoperatively using ICG tissue angiography. 5 mg indocyanine green were intravenously administered. Fluorescence angiography was evaluated in real time using the PinPoint (Novadaq, Canada) imaging system. The study was approved by the local ethics committee. RESULTS: ICG fluorescence angiography was performed uneventfully in all cases. There was no case of postoperative hypoparathyroidism when at least one parathyroid gland with high fluorescence intensity was preserved. In 4 cases, only low fluorescence intensity was detected in the remaining parathyroid glands after completing the resection. All 4 patients received activated vitamin D3 prophylactically. Two of 4 developed symptomatic hypocalcaemia due to temporary hypoparathyroidism. CONCLUSION: Implementation of ICG fluorescence angiography can help in predicting and therefore preventing postoperative hypoparathyreoidism after total thyreoidectomy. If a well vascularised parathyroid gland with high ICG fluorescence intensity can be secured, calcium substitution and postoperative prophylaxis of hypoparathyreoidism may become obsolete in the future.

Stability and degradation of indocyanine green in plasma, aqueous solution and whole blood.

Fluorescence-based imaging has evolved into an important technology during recent years. Specifically indocyanine green (ICG) has invaded most fields of diagnostic and interventional medicine. Considering the numerous advantages of the substance like the rapid degradation and rare adverse reactions, ICG is currently the most commonly used fluorescing agent. High-performance liquid chromatography (HPLC) was used for measuring absorbance and fluorescence of ICG and its potential degradation compounds. Stability and degradation were evaluated under light exposure or in darkness at various temperatures. Under these conditions, degradation of ICG was evaluated over a period of 11 days. Additional, stability measurements of ICG were performed in EDTA whole blood samples at 37 °C incubation temperature while monitoring. Furthermore, we used mass spectrometric (MS) and nuclear magnetic resonance (NMR) analyses for the identification of supposed ICG degradation compound. Potential quenching effect of ICG was examined in aqueous and plasma solutions at concentrations ranging from 0.01-100 µg ml-1. When diluted in water and stored at 4 °C in the dark, ICG is stable for three days with only 20% of fluorescence intensity lost in this time-span. ICG incubated at 37 °C in whole blood under light exposure is stable for 5 h. In our study we observed the degradation of ICG into two degradation compounds with a mass of m/z 785.32 and m/z 1501.57, respectively. Based on our observations we suggest that ICG should be used within one or two days after preparation, if the ICG solution is stored at 4 °C.

Indocyanine Green Tissue Angiography Can Reduce Extended Bowel Resections in Acute Mesenteric Ischemia.

PURPOSE: Surgical exploration and bowel resection are frequently required for treating non-occlusive mesenteric ischemia. Intraoperative evaluation of intestinal perfusion is subjective and challenging. In this feasibility study, ICG fluorescence angiography was performed in order to evaluate intestinal perfusion in patients with acute mesenteric ischemia. METHODS: This is a retrospective analysis of 52 patients who were operated for acute mesenteric ischemia using ICG fluorescence angiography. Patients with occlusive disease requiring recanalization were excluded. The SPY and PinPoint imaging systems were used for open and laparoscopic surgery, respectively. Intraoperative macroscopic assessment of perfusion was compared with the ICG angiography results. RESULTS: Surgical exploration was performed for ischemia of the colon (n = 12), the small bowel (n = 23), or both (n = 16). One patient had ischemia of the esophagus and stomach. All patients had a preoperative CT angiography to rule out stenosis or occlusion of the mesenteric vessels. In 18 cases (34.6%), ICG fluorescence angiography provided information that was supplemental to macroscopic evaluation, but most patients did not survive the postoperative course. However, in six of those cases (11.5%), ICG angiography led to a major change in operative strategy resulting in a significant clinical benefit for those patients. For two cases, ICG fluorescence produced false negative results. DISCUSSION: ICG tissue angiography is feasible and technically reliable for evaluating intestinal perfusion in acute mesenteric ischemia and led to a significant clinical benefit in 11% of our patients. A relevant discrepancy between surgical visual assessment and fluorescence angiography was found in 35% of the cases, which may help to define resection margins more accurately and thus support surgical decision-making.

The evaluation of circulating endothelial progenitor cells and related angiogenic markers as prognostic factors in soft-tissue tumors.

INTRODUCTION: Neovascularisation is a critical step in the progression of malignant tumors. Circulating endothelial progenitor cells (cEPC) have been proposed as surrogate markers of vasculogenesis in malignancies. In this project, we studied the impact of tumor-specific therapy on cEPC and associated angiogenic factors in patients with soft tissue tumors. MATERIALS AND METHODS: Fifty-three patients with soft tissue tumors (25 soft tissue sarcomas, 19 GIST, 9 desmoids) and 15 healthy controls were included. Blood samples were obtained at two time points, before and 8 weeks after start of tumor-specific therapy. Peripheral blood mononuclear cells (PBMCs) were isolated. cEPCs were characterised as CD34+, CD133+, CD45dim, CD31+ and vascular endothelial growth factor 2 (VEGFR-2) positive cells. Serum concentrations of VEGF-A and angiopoetin-2 were determined by enzyme-linked immunosorbent assay. RESULTS: VEGF-A and Ang-2 concentrations were significantly higher in tumor patients than in healthy controls in both samples (p < .01). Sarcoma patients with progressive disease developed a significant increase in cEPC levels between the two blood samples compared to those with stable disease (p = .002). GIST patients with progressive tumor or metastatic disease showed significant increase in VEGF-A values (p = .01). DISCUSSION: The pre-treatment values of the angiogenic markers did not correlate with the clinical course of the disease. However, cEPCs levels were significantly higher in sarcoma patients with progressive disease compared to those with stable disease and should be further evaluated as early markers of disease progression in sarcoma patients. VEGF-A and angiopoetin-2 clearly play a role as mediators of the vasculogenesis contributing to tumor progression.