Intraoperative Wound Irrigation for the Prevention of Surgical Site Infection After Laparotomy: A Randomized Clinical Trial by CHIR-Net.

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.

Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

BACKGROUND: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. METHODS: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001). CONCLUSIONS: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.

The impact of intraoperative MRI on cranial surgical site infections-a single-center analysis.

PURPOSE: The use of intraoperative MRI (ioMRI) contributes to an improved extent of resection. Hybrid operating room MRI suites have been established, with the patient being transferred to the MRI scanner. In the present descriptive analysis, we compared the rate of surgical site infections (SSI) after intracranial tumor surgery with and without the use of ioMRI. METHODS: In this retrospective study, we included 446 patients with open craniotomy performed for brain tumor surgery. One hundred fourteen patients were operated on with the use of ioMRI between June 1, 2018, and June 30, 2019 (group 1). During the same period, 126 patients were operated on without ioMRI (group 2). As an additional control group, we analyzed 206 patients operated on from February 1, 2017, to February 28, 2018 when ioMRI had not yet been implemented (group 3). RESULTS: The rate of SSI in group 1 (11.4%), group 2 (9.5%), and group 3 (6.8%) did not differ significantly (p = 0.352). Additional resection after ioMRI did not result in a significantly elevated number of SSI. No significant influence of re-resection, prior radio-/chemotherapy, blood loss or duration of surgery was found on the incidence of SSI. CONCLUSION: Despite the transfer to a non-sterile MRI scanner, leading to a prolonged operation time, SSI rates with and without the use of ioMRI did not differ significantly. Hence, advantages of ioMRI outweigh potential disadvantages as confirmed by this real-life single-center study.

Improvement of synaptic plasticity and cognitive function in RASopathies-a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS).

BACKGROUND: Cognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies. METHODS: Within this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I-III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV). DISCUSSION: The study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition. TRIAL REGISTRATION: The clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www. CLINICALTRIALS: gov ; date of registration: 04/11/2018) and in EudraCT (number 2016-005022-10).

Surgical site infection prevention in abdominal surgery: is intraoperative wound irrigation with antiseptics effective? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Surgical site infection (SSI) after laparotomy still represents the most frequent postoperative complicationin abdominal surgery. The effectiveness of reducing SSI rates by intra-operative irrigation of the incisional wound with antiseptic solutions or saline has been much debated, and recommendations on its use are divergent. Therefore, we aim to conduct a systematic review and meta-analysis, focusing specifically on procedures by laparotomy and considering recent evidence only. METHODS AND ANALYSIS: The systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. On 1 July 2022, PubMed/MEDLINE, Cochrane, Central Register of Controlled Trials and EMBASE were searched for the following predefined terms: (Surgical site infection) AND ((irrigation) OR (wound irrigation) OR (lavage)) AND ((abdominal surgery) OR (laparotomy). The search was limited to peer-revied publications, dating after 1 January 2000 in English or German language. Systematic reviews and meta-analyses were included for reference screening. Case reports, case series, non-systematic reviews and studies without follow-up information were excluded. The primary outcome is the rate of postoperative SSI after abdominal surgery by laparotomy. Meta-analysis is pooled using the Mantel-Haenszel method for random effects. The risk of bias in randomised studies will be assessed using the Cochrane developed RoB 2-tool, and the ROBINS-I tool for non-randomised studies. Completion of the analysis and publication is planned in March 2023. ETHICS AND DISSEMINATION: Ethical approval is not necessary for this study, as no new data will be collected. The results of the final study will be published in a peer-reviewed open-access journal. PROSPERO REGISTRATION NUMBER: CRD42022321458.

Peritoneal antiseptic irrigation to prevent surgical site infection after laparotomy for hepatobiliary or gastrointestinal surgery (PAISI)-protocol for a randomized controlled study.

BACKGROUND: Postoperative surgical site infections (SSIs) remain common after laparotomy for resections of the gastrointestinal or hepatobiliary tract. Especially organ/space infections (CDC class III SSI) can be life-threatening, require relaparotomy, intensive care or interventional drainage of intraabdominal abscesses. The PAISI study aims to investigate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce the SSI rates following laparotomy for resections of the gastrointestinal or hepatobiliary tract, compared to standard irrigation with physiological electrolyte solution (Ringer's solution). Secondarily, to evaluate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce postoperative morbidity and mortality as well as the rate of re-operations and length of hospital stay. METHODS: PAISI is a prospective, randomized, observer- and patient-blinded, monocentric, two-arm surgical study in an adaptive parallel groups design, comparing peritoneal and wound irrigation with NaOCl/HOCl (50/50ppm) solution to irrigation with Ringer's solution. The primary endpoint of the study is the SSI rate within 30 days postoperatively. Since there is no data on incidence rates from randomized clinical trials, the rates for sample size calculation were estimated according to the clinical experience at our institution. Therefore, the study design includes one unblinded look at the data by a second statistician, which will be performed after half of the patients reached the primary endpoint. This interim information will be used to check the assumptions and if needed, the sample size will be adjusted. The O'Brien-Fleming spending function is used to determine the efficacy test boundary and the non-binding futility boundary. The one-sided z-test (Group sequential test of two proportions) at the 2.5% significance level with a total of two looks at the data will have overall 80% power. DISCUSSION: The results of this study will provide high-level evidence for future research and clinical recommendations regarding the use of NaOCl/HOCl solution in abdominal surgery and provide the participating patients the opportunity of a potentially improved treatment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028037. Registered on 27 May 2022.

Lumbar dynamic pedicle-based stabilization versus fusion in degenerative disease: a multicenter, double-blind, prospective, randomized controlled trial.

OBJECTIVE: Fusion is the standard of treatment for degenerative lumbar symptomatic instabilities. Dynamic stabilization is a potential alternative, with the aim of reducing pathological motion. Potential advantages are a reduction of surgical complexity and morbidity. The aim of this study was to assess whether dynamic stabilization is associated with a higher degree of functional improvement while reducing surgical complexity and thereby surgical duration and perioperative complications in comparison with lumbar fusion. METHODS: This was a multicenter, double-blind, prospective, randomized, 2-arm superiority trial. Patients with symptomatic mono- or bisegmental lumbar degenerative disease with or without stenosis and instability were randomized 1:1 to instrumented fusion or pedicle-based dynamic stabilization. Patients underwent either rigid internal fixation and interbody fusion or pedicle-based dynamic stabilization. The primary endpoint was the Oswestry Disability Index (ODI) score, and secondary endpoints were pain, health-related quality of life, and patient satisfaction at 24 months. RESULTS: Of 293 patients randomized to fusion or dynamic stabilization, 269 were available for analysis. The duration of surgery was significantly shorter for dynamic stabilization versus fusion, and the blood loss was significantly less for dynamic stabilization (380 ml vs 506 ml). Assessment of primary and secondary outcome parameters revealed no significant differences between groups. There were no differences in the incidence of adverse events. CONCLUSIONS: Dynamic pedicle-based stabilization can achieve similar clinical outcome as fusion in the treatment of lumbar degenerative instabilities. Secondary failures are not different between groups. However, dynamic stabilization is less complex than fusion and is a feasible alternative.

Results of a Clinical Scoring System Regarding Symptoms and Surgical Treatment of Isolated Unilateral Zygomatico-Orbital Fractures: A Single-Centre Retrospective Analysis of 461 Cases.

Systematic assessment of computed tomography (CT) scans and clinical symptoms is necessary to quickly indicate the correct treatment of zygomatico-orbital (ZMO) fractures. For this purpose, a clinical scoring system (=Clinical Score) was developed and correlated with CT scans to analyse its validity. Every operated, isolated, and unilateral ZMO fracture between January 2012 and December 2016 was screened retrospectively, including patient and treatment data. All available CT scans were analysed, and the grade of dislocation was measured for each case and plane. Four hundred and sixty-one cases were included and showed a median surgery time of 66.0 min (5.0−361.0) and a median postoperative hospital stay of three days (0−25). The distribution of gender, aetiologies and age groups was significantly different (each p = 0.001), and the aetiology had a significant influence on the Clinical Score (p = 0.038). The degree of dislocation in the coronary and sagittal planes correlated significantly with the Clinical Score with regard to the orbital involvement (p < 0.001, ρ = 0.566; p < 0.001, ρ = 0.609). The simple, quick, and easy-to-apply Clinical Score showed a significant correlation with the most important planes in CT scans as well as with the clinical course. It may facilitate fast risk stratification of the patient. However, the validity of the proposed score in determining indications must now be evaluated in a prospective setting, including both operated and non-operated fractures.

Preoperative Peroneal Artery Perforator Mapping Using Indocyanine Green Angiography: A Prospective Clinical Trial.

BACKGROUND: Perforator imaging is a prerequisite in preoperative planning of the peroneal perforator flap and the fibula skin island. Although reports indicate that indocyanine green angiography assessment method might be advantageous over conventional ultrasound-based techniques (i.e., Doppler and color duplex), in practice, clear evidence is lacking. Thus, a comparative assessment of the utility of indocyanine green angiography and ultrasound-based techniques in the identification of suitable lower leg skin perforators was performed. METHODS: A prospective clinical cohort study with a series of 12 consecutive patients was conducted to assess indocyanine green angiography, Doppler ultrasound, and color duplex ultrasound techniques for preoperative perforator detection in the lower leg before free fibula flap harvest. Anatomical dissection served as a reference. Parameters measured were perforator spatial distance to the reference (precision), operative time expenditure, and ease of device usage for assessment/outcomes. RESULTS: This study included 12 patients, with a total of 27 perforators. Exhibition of technique sensitivity and positive predictive values were as follows: indocyanine green angiography, 93 percent and 100 percent; Doppler ultrasound, 82 percent and 82 percent; and color duplex ultrasound, 89 percent and 86 percent, respectively. With regard to the indocyanine green angiography technique, the distance to the actual perforator location was significantly shorter, which aided detection and lesser time expenditure during operation. CONCLUSIONS: The indocyanine green angiography technique proved to have high precision, sensitivity, positive predictive value, and easy-to-use capabilities because of its exceptional spatial and temporal information, compared to the conventional, ultrasound-based techniques. Therefore, indocyanine green angiography is superior for preoperative perforator imaging of the lateral lower leg. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

A bitter pill to swallow - Polypharmacy and psychotropic treatment in people with advanced dementia.

BACKGROUND: Polypharmacy is common in people with dementia. The use of psychotropic drugs (PDs) and other, potentially inappropriate medications is high. The aims of this cross-sectional study were 1) to investigate the use of drugs in people with advanced dementia (PWAD), living at home or in long term care (LTC); 2) to focus on PD use; and 3) to identify determinants of PD use. METHODS: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for people in advanced and terminal stages of YOD and LOD in Germany). 191 PWAD were included. All drugs that were administered at the date of the examination were recorded. Multiple logistic regression analysis identified determinants of PD use. RESULTS: 96% of PWAD received medication with a median number of four drugs. 49.7% received five or more drugs. According to the Beers Criteria 39% of PWAD ≥ 65 years received at least one potentially inappropriate medication. 79% of PWAD were treated with PDs. Older PWAD and PWAD living in LTC facilities received significantly more drugs than younger PWAD, and PWAD living at home, respectively. Dementia etiology was significantly associated with the use of antipsychotics, antidepressants and sedative substances. Place of living was associated with the use of pain medication. Behavioral disturbances were associated with the use of antipsychotics and sedative substances. CONCLUSIONS: To mitigate the dangers of polypharmacy and medication related harm, critical examination is required, whether a drug is indicated or not. Also, the deprescribing of drugs should be considered on a regular basis. TRIAL REGISTRATION: Clinicaltrial.gov, NCT03364179 . Registered 6 December 2017.

Acute Appendicitis: Trends in Surgical Treatment­A Population-Based Study of Over 800 000 Patients.

BACKGROUND: Appendectomy is the gold standard for treatment of acute appendicitis. However, recent studies favor primary antibiotic therapy. The aim of this observational study was to explore changes in the numbers of operations for acute appendicitis in the period 2010-2017, paying special attention to disease severity. METHODS: Data from diagnosis-related group statistics were used to analyze the trends, mortality, and complication rates in the surgical treatment of appendicitis in Germany between 2010 and 2017. All cases of appendectomy after a diagnosis of appendicitis were included. RESULTS: Altogether, 865 688 inpatient cases were analyzed. The number of appendectomies went down by 9,8%, from 113 614 in 2010 to 102 464 in 2017, while the incidence fell from 139/100 000 in 2010 to 123/100 000 in 2017 (standardized by age group). This decrease is due to the lower number of operations for uncomplicated appendicitis (79 906 in 2017 versus 93 135 in 2010). Hospital mortality decreased both in patients who underwent surgical treatment of complicated appendicitis (0.62% in 2010 versus 0.42% in 2017) and in those with a complicated clinical course (5.4% in 2010 versus 3.4% in 2017). CONCLUSION: Decisions on the treatment of acute appendicitis in German hospitals follow the current trend towards non-surgical management in selected patients. At the same time, the care of acute appendicitis has improved with regard to overall hospital morbidity and hospital mortality.

Radiooncological View on Therapy Outcome after Multidisciplinary Treatment of Sinonasal Tumors.

PURPOSE: We report the outcome of a mono-institutional retrospective study of sinonasal carcinoma with the primary focus on GTV (gross tumor volume) and the effect of radiotherapy. METHODS: 53 patients with sinonasal carcinoma and that of the nasal cavity, paranasal sinus or both except lymphoma were included. All patients were treated between 1999 and 2017. For tumor volume delineation, all pre-therapeutic images were fused to the planning CT (computed tomography). RESULTS: The median follow-up was 17 months [0.3-60], the median age 60 years, 35 males and 18 females were included. Squamous cell carcinoma (SCC) (60.4%) was the predominant histology, followed by adenocarcinoma (15.1%). The mean composite OS (overall survival) time was 33.3 ± 3.5 months. There was no significant difference in the 5 y composite OS between tumor localization or radiotherapy setting. The simultaneous integrated boost concept showed a trend towards improving five-year composite OS compared to the sequential boost concept. The only factor with a significant impact on the 5 y composite OS rate was the pre-therapeutic GTV (cutoff 75 cm3; p = 0.033). The GTV ≥ 100 cm3 has no effect on the 5 y composite OS rate for SCC. CONCLUSIONS: The pre-therapeutic GTV is a prognostic factor for five-year composite OS for the entire group of patients with sinonasal tumors, influencing the outcome after completion of all treatment strategies. The GTV seems to not influence five-year composite OS in SCC. For this rare tumor entity, an intensive, multidisciplinary discussion is essential to finding the best treatment option for the patient.

How Do Persons with Young and Late Onset Dementia Die?

BACKGROUND: End of life symptoms and symptom management as well as the quality of dying (QoD) of persons with advanced dementia (PWAD) have not yet been systematically studied in Germany. OBJECTIVE: 1) To investigate symptoms, treatment and care at the end of life, advance care planning, and circumstances of death of recently deceased PWAD; 2) To determine whether there are differences between young and late onset dementia (YOD and LOD). METHODS: The study was performed in the context of the project EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of Young-onset and Late-Onset dementia in Germany). Closest relatives of recently deceased patients with advanced YOD (N = 46) and LOD (N = 54) living at home or in long term care were interviewed. RESULTS: Circumstances of death, symptoms, and treatment appeared to be similar between YOD and LOD, except that persons with LOD had significantly more somatic comorbidities and were admitted to hospital in the last three months of life more often than persons with LOD. At end of life, 60% of PWAD appeared to be "at peace". Difficulty swallowing, gurgling, shortness of breath, and discomfort were observed most frequently. Large interindividual differences in suffering and QoD were present. Determinants of QoD were not identified. CONCLUSION: Our findings suggest that low QoD was caused by inadequate recognition and/or insufficient treatment of burdensome physical and emotional symptoms. PWADs' needs should be assessed regularly, and strategies focusing on treatment and implementing support for both the patient and caregiver must be established.

Quality of Life in Advanced Dementia with Late Onset, Young Onset, and Very Young Onset.

BACKGROUND: Advanced stages of dementia are characterized by severe cognitive and physical impairment. It has not yet been investigated whether persons with young onset dementia (YOD) and late onset dementia (LOD) differ in advanced disease stages. OBJECTIVES: To compare quality of life (QoL) between persons with advanced YOD and LOD; to explore the determinants of QoL; to investigate whether YOD and LOD differ with regard to symptoms and care. METHODS: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of YOD and LOD in Germany). Persons with advanced dementia (PWAD) were assessed and caregivers were interviewed. QoL was measured with the proxy rating Quality of Life in Late Stage Dementia (QUALID) scale. RESULTS: 93 persons with YOD and 98 with LOD were included. No significant differences in QoL were detected. Determinants of QoL were similar in YOD and LOD. Behavioral and psychological symptoms of dementia (BPSD), suffering and other distressing symptoms were associated with a lower QoL. In YOD but not in LOD antipsychotic treatment was associated with low QoL. The group of persons who were younger than 65 years at the time of the study visit experienced significantly more distressing symptoms than older PWAD. CONCLUSION: Overall, persons with advanced YOD do not appear to be disadvantaged compared to old and oldest PWAD. Special attention, however, must be paid to the group of the very young persons who seem to be particularly vulnerable.

Retrospective analysis of complications in 190 mandibular resections and simultaneous reconstructions with free fibula flap, iliac crest flap or reconstruction plate: a comparative single centre study.

OBJECTIVES: The purpose of this study was to evaluate the incidence of complications following mandibular reconstruction and to analyse possible contributing factors. MATERIALS AND METHODS: Clinical data and computed tomography scans of all patients who needed a mandibular reconstruction with a reconstruction plate, free fibula flap (FFF) or iliac crest (DCIA) flap between August 2010 and August 2015 were retrospectively analysed. RESULTS: One hundred and ninety patients were enrolled, encompassing 77 reconstructions with reconstruction plate, 89 reconstructions with FFF and 24 reconstructions with DCIA flaps. Cutaneous perforation was most frequently detected in the plate subgroup within the early interval and overall (each p = 0.004). Low body mass index (BMI) and total radiation dosage were the most relevant risk factors for the development of analysed complications. CONCLUSIONS: Microvascular bone flaps have overall less skin perforation than reconstruction plates. BMI and expected total radiation dosage have to be respected in choice of reconstructive technique. CLINICAL RELEVANCE: A treatment algorithm for mandibular reconstructions on the basis of our results is presented.

Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II-IV: a multicenter retrospective case series.

INTRODUCTION: Primary malignant spinal astrocytomas present rare oncological entities with limited median survival and rapid neurological deterioration. Evidence on surgical therapy, adjuvant treatment, and neurological outcome is sparse. We aim to describe the treatment algorithm and clinical features on patients with infiltrating intramedullary astrocytomas graded WHO II-IV. METHODS: The following is a multicentered retrospective study of patients treated for spinal malignant glioma WHO II-IV in five high-volume neurosurgical departments from 2008 to 2019. Pilocytic astrocytomas were excluded. We assessed data on surgical technique, perioperative neurological status, adjuvant oncological therapy, and clinical outcome. RESULTS: 40 patients were included (diffuse astrocytoma WHO II n = 11, anaplastic astrocytoma WHO III n = 12, WHO IV n = 17). Only 40% were functionally independent before surgery, most patients presented with moderate disability (47.5%). Most patients underwent a biopsy (n = 18, 45%) or subtotal tumor resection (n = 15, 37.5%), and 49% of the patients deteriorated after surgery. Patients with WHO III and IV tumors were treated with combined radiochemotherapy. Median overall survival (OS) was 46.5 months in WHO II, 25.7 months in WHO III, and 7.4 months in WHO IV astrocytomas. Preoperative clinical status and WHO significantly influenced the OS, and the extent of resection did not. CONCLUSION: Infiltrating intramedullary astrocytomas WHO II-IV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.

Comparison between Different Perforator Imaging Modalities for the Anterolateral Thigh Perforator Flap Transfer: A Prospective Study.

BACKGROUND: Perforator imaging is routinely performed before perforator flap harvest. Hand-held Doppler (hhD) and color duplex ultrasonography (CDU) are currently the most popular radiation-free methods for this purpose that can be applied by the surgeon alone. The aim of this study was to compare the accuracy, reliability, and feasibility of hhD and CDU with indocyanine green angiography (ICGA) in the anterolateral thigh perforator flap (ALTPF). METHODS: All consecutive ALTPF procedures between May 2017 and April 2018 were included in this prospective study. The perforators were visualized by three investigators independently and randomized, applying hhD, CDU, and ICGA. The presence and the distance to the identified perforator were registered. Further, body mass index (BMI), American Society of Anesthesiologists-status, and the patient's history regarding smoking, alcohol use, and diabetes mellitus were registered alongside gender and age to analyze possible confounders. RESULTS: A total of 12 patients were enrolled with a median age of 67 (52-87) years. In total, 30 perforators were detected intraoperatively as well as with the ICGA. The latter visualized the perforators significantly more precisely than hhD and CDU (p < 0.001 and p = 0.001). The sensitivity and positive predictive value were 67 and 62% for hhD, 73 and 64% for CDU, and 100 and 100% for ICGA, respectively. CONCLUSION: According to this study, ICGA visualized perforators more accurately than the standard methods hhD and CDU. Further, it was associated with the highest sensitivity and positive predictive value. ICGA consistently delivered excellent results, whereas hhD and CDU showed variability.

Milk cloud appearance-a characteristic sign of fibrous dysplasia on contrast-enhanced MR imaging.

OBJECTIVE: To evaluate contrast-enhanced T1-weighted magnetic resonance (MR) images in histologically proven fibrous dysplasia (FD) for the prevalence of "milk cloud appearance" and its association with ground-glass appearance (GGA) on radiography or computed tomography (CT). METHODS: For this retrospective cohort study, 37 patients with histologically proven FD imaged preoperatively with contrast-enhanced MR imaging and radiography or CT were identified at our institution. Three radiologists independently evaluated MR images for the presence of milk cloud appearance on T1-weighted contrast-enhanced images, sites of skeletal involvement, type of bone involved, uni- vs. multifocality, mono- vs. polyostotic disease, maximum diameter, proportion of bone involved, expansile remodeling, and T2 homogeneity. The presence or absence of GGA on radiography or CT was determined in consensus. Inter-reader agreement was evaluated for milk cloud appearance using Cohen's kappa, and associations between milk cloud appearance and other imaging parameters were tested using Spearman's rho. RESULTS: Among the 37 histologically proven FD lesions, GGA was identified in 70% of the lesions, while milk cloud appearance was found in 82% of the lesions. Inter-reader agreement for milk cloud appearance on MR imaging was good to excellent (κ 0.65, 0.82, and 0.8). A significant correlation was found between milk cloud appearance and GGA (ρ = 0.31, p < 0.001). CONCLUSION: Milk cloud appearance is a characteristic sign of FD on contrast-enhanced T1-weighted MR images. Recognition of this feature may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of FD. KEY POINTS: • Fibrous dysplasia displays a characteristic feature on contrast-enhanced T1-weighted MR imaging: milk cloud appearance. • Milk cloud appearance correlates well with the radiographic or CT finding of ground-glass appearance. • Recognition of milk cloud appearance on contrast-enhanced MR imaging may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of fibrous dysplasia.

Circulating cKIT and PDGFRA DNA indicates disease activity in Gastrointestinal Stromal Tumor (GIST).

This prospective trial aimed to investigate whether tumor-specific cKIT and PDGFRA mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active GIST, and whether detection indicates disease activity. We included 25 patients with active disease and cKIT or PDGFRA mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele-specific ligation (L-)PCR and droplet digital (d)PCR. CtDNA harboring tumor-specific cKIT or PDGFRA mutations was detected at least once in 16 out of 25 patients using L-PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies/ml) and the mutant allele frequency (MAF; in percent of wild-type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (ρ = 0.3719 and 0.408, respectively, p < 0.0001) and response status (ρ = 0.3939 and 0.392, respectively, p < 0.0001 and p < 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L-PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with GIST and should be incorporated as companion biomarker in future prospective trials.