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.

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.

[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.

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.

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.

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.

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.

[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.

Dosing of indocyanine green for intraoperative laser fluorescence angiography in kidney transplantation.

OBJECTIVE: Sufficient blood supply is a crucial factor determining postoperative allograft function in kidney transplantation. Therefore, besides the surgeon's individual impression, a method for evaluating the quality of the organ's microperfusion is required. Laser fluorescence angiography with indocyanine green (ICG) is an emerging tool for this purpose. However, no reproducible quantification of ICG fluorescence has been performed in transplantation so far. METHODS: This retrospective two-center study was designed to evaluate the dosing of ICG for intraoperative laser fluorescence angiography in kidney transplantation. The Spy Elite® system (NOVADAQ, Canada) was employed for quantitative assessment of allograft microperfusion. ICG was administered systemically 5 minutes after reperfusion applying doses between 0.25 and 0.01 mg ICG per kg body weight. Quantitative assessment was performed with the implemented SPY-Q Software. RESULTS: A total of 57 kidney recipients were included in two centers. The generated curves showing ICG IN and EgR were not evaluable due to oversensing when doses exceeded 0.02 mg per kg body weight. CONCLUSIONS: Fluorescence angiography with ICG is an emerging tool for the intraoperative quality control and evaluation of microperfusion in kidney transplantation. A dose of 0.02 mg ICG per kg body weight is recommended to ensure the quantitative assessment with SPY-Q.

Src activity is increased in gastrointestinal stromal tumors--analysis of associations with clinical and other molecular tumor characteristics.

BACKGROUND: Increased activity of Src has been found in several human cancers, and often is associated with poor clinical outcome. The present study aimed to determine whether Src activity is increased in gastrointestinal stromal tumors (GIST), and whether it correlates with established tumor or patient characteristics and prognosis. METHODS: Tumor/normal tissues of 29 patients were analyzed for Src activity/protein with kinase assays, and for VEGF/VEGFR with immunohistochemical staining. RESULTS: Src activity was higher in tumor than in normal tissues (P = 0.093). However, when imatinib responders were excluded from the analyses, it was significantly higher in the tumor tissue (P = 0.017). Additionally, it was higher in primary compared to recurrent tumors or metastasis (P = 0.04). Univariate survival analysis showed a longer overall survival for patients with high Src activity (P = 0.038). In multivariate analysis, the response to imatinib treatment was the only survival-influencing factor (P = 0.072). CONCLUSIONS: Src activity is increased in GIST. In contrast to most other tumor entities, it does not correlate with poor clinical outcome, but decreases during the progression from primary tumor to recurrence and metastasis, especially under therapy with imatinib. Additionally, our results show that higher Src activity is associated with longer overall survival.

Oncological outcome of primary non-metastatic soft tissue sarcoma treated by neoadjuvant isolated limb perfusion and tumor resection.

BACKGROUND: Isolated limb perfusion (ILP) is an effective limb salvage strategy in patients with advanced soft tissue sarcoma (STS) where surgery alone would result in significant functional morbidity or mandate an amputation. Most previous reports of patients undergoing ILP focus on limb salvage rates rather than local and distant relapse rates. Here, we report the oncological outcome of sarcoma patients treated by ILP and surgery. METHODS: Data were retrieved from prospective ILP databases from two ILP centers following similar ILP techniques and surgical approaches. Only patients with primary, intermediate, or high grade non-metastatic STS were included. RESULTS: The cohort comprised 90 patients. Median follow-up was 39 months (range 3-165 months). Median tumor size was 11 cm (range 5-34). Twenty of 90 (22%) patients underwent prior debulking surgery outside the centers. Twenty-nine of 90 (32%) had postoperative irradiation. Four of 90 underwent amputation either related to local recurrence or irresectability, 4 of 90 underwent amputation for treatment-related complications. Fifteen of 83 (18%) patients had local recurrences after ILP and limb sparing surgery, 39 of 90 (43%) developed metastatic disease. Twenty-two of 90 (24%) died of disease. CONCLUSION: Preoperative ILP and tumor resection resulted in good local control in a cohort of high-risk STS patients.

Alterations of circulating bone marrow-derived VEGFR-2+ progenitor cells in isolated limb perfusion with or without rhTNF-α.

BACKGROUND: Circulating endothelial progenitor cells (cEPCs) as recruited to the angiogenic vascular system of malignant tumors have been proposed as a biomarker in malignancies. The effect of antitumor chemotherapy on cEPCs is not fully understood. We examined the level of cEPCs, vascular endothelial growth factor (VEGF), and angiopoietin-2 in the blood of sarcoma and melanoma patients before and after isolated limb perfusion (ILP) with or without recombinant human tumor necrosis factor-α (rhTNF-α). METHODS: Twenty-two patients, 11 each with soft tissue sarcoma or recurrent melanoma of the limb, were recruited. ILP was performed with rhTNF-α/melphalan (TNF) or melphalan only (no TNF). Fifteen healthy volunteers served as control subjects. Blood was sampled before and up to 6 weeks after ILP. Peripheral blood mononuclear cells were isolated by density gradient centrifugation, and annexin V-negative cells were characterized as cEPCs by triple staining for CD133(+), CD34, and VEGFR-2(+). RESULTS: Before treatment, cEPC numbers were significantly increased in sarcoma (0.179 ± 0.190 %) and melanoma patients (0.110 ± 0.073 %) versus healthy controls (0.025 ± 0.018 %; P < 0.01), but did not differ significantly between sarcoma and melanoma patients. cEPC decreased significantly after ILP in patients with no TNF compared to pretreatment values (P < 0.05) and were significantly lower at 4 h, 48 h, and 1 week compared to ILP with TNF (P < 0.05). Values 6 weeks after ILP were significantly lower than before ILP in both investigated groups (P < 0.01). CONCLUSIONS: ILP with TNF results in activation of bone marrow-derived EPCs compared to ILP without TNF. Alteration of cEPCs and angiopoietin-2 by rhTNF-α might account for the cytotoxicity and hemorrhagic effects on tumor vessels during limb perfusion procedures.

Immunotargeting of the pulmonary endothelium via angiotensin-converting-enzyme in isolated ventilated and perfused human lung.

Vascular immunotargeting of catalase via angiotensin-converting-enzyme (ACE) attenuated lung ischemia reperfusion injury in the rat. As this might be a promising modality for extension of the viability of human lung grafts for transplantation we tested the hypothesis whether anti-ACE antibodies are suitable for human lung protection within the model of isolated perfused and ventilated human lung resections. Right after surgery for lung cancer, human lung specimens were isolated, ventilated and perfused under physiological conditions with 500 µg of either mouse monoclonal antibodies (mAb) to human ACE (9B9, I2H5, 3G8) or non-immune mouse IgG (as a negative control) followed by wash-out perfusion. Perfusion pressure, pH and lung weight gain were measured before and during perfusion. After mAb perfusion and wash-out perfusion period lung tissue was tested for the uptake of mAbs by immunohistochemistry and by enzyme-capture technique. Furthermore, antibody concentration and ACE shedding were measured within the perfusate. We found that ACE activity in tumor and normal lung tissue did not differ between the groups perfused with different mAbs. However, ACE activity in normal lung tissue (17.0 ± 6.0 U/g) was significantly higher compared to tumor tissue (6.0 ± 3.0; p < 0.01). Absolute retaining of mAbs was with 1.3 ± 1.1% of injected dose per gram of tissue in normal lung tissue, 0.7 ± 0.7% of injected dose per gram of tumor tissue and was significantly higher compared to non-immune mouse IgG (0.1 ± 0.1%/g; p < 0.01). Anti-ACE mAbs concentration in the perfusate dropped significantly to 47 ± 11% (p < 0.001) at 40 min of perfusion. No significant difference between different anti-ACE mAbs in the depletion from perfusate has been observed. mAb 9B9 showed the most intense immunostaining (i.e., most significant lung uptake) after each experiment in normal and tumor lung tissue compared to mAbs i2H5 and 3G8 (p < 0.01). These results validate the possibility of immunotargeting of pulmonary endothelium in the human lung tissue by anti-ACE mAbs under in vivo conditions. Furthermore, the model might be useful to investigate targeted therapies in lung cancer without side effects for the patient.

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.

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.

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.

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.