Discovery of Lijianmin-Chengkun Complexes and Their Oncological Application in Osseous and Intraarticular Lesions Around the Knee

Objective: This research aims to refresh the limited understanding about the canal and vascular structures within the epiphysis and metaphysis of the tibia and femur and their oncological significance.Methods: This study was started with characterization of a novel structure using radiographs and anatomic dissections, followed by a descriptive clinical study with 55 participants to investigate the effects of tumors on this novel discovery and a retrospective cohort study with 82 participants to investigate whether the structure would be a risk factor for tumor recurrence after the curettage of giant cell tumor of bone.Results: A new anatomical knee structure, the Lijianmin-Chengkun (LC) complex, was discovered in healthy adults, and its clinical implications were examined in this study. This new-found anatomical structure is composed of an epiphyseal and metaphyseal canal which surrounds a blood vessel, foramen, and foramen-covered synovium. All LC complexes showed similar radiographical, anatomical, and histological characteristics and were located within specific tibial and femoral intercondylar regions. These LC complexes seem to facilitate tumor residue and extension and may be a risk factor for tumor recurrence after curettage of femoral and tibial giant cell tumors (P = 0.031).Conclusion: The LC complexes are related to local tumor recurrence and bidirectional tumor dissemination between intraosseous and intraarticular regions. These findings have opened up a new perspective and may provide new targets for intervention in malignant and aggressive tumors around the knee joint.

The Profiling of Circulating Tumor DNA in Pediatric Mature B-Cell Non-Hodgkin Lymphoma（B-NHL）: A Multicenter and Prospective Clinical Study

Background Next-generation sequencing (NGS) based on liquid biopsy has been an emerging technology to identify tumor-specific genetic aberrations in adult lymphoma. However, there were few studies on the genomic profiling of plasma circulating tumor-derived DNA (ctDNA) in pediatric mature B-NHL. Methods Paraffin-embedded tissue (FFPE) and plasma samples from the newly diagnosed patients were collected and sequenced by 475 genes panel before, during and post of treatment. Clinical stage system, risk stratification and treatment of pediatric mature B-NHL followed a the modified BFM-95 protocol. Results A total of 53 pediatric mature B-NHLs were enrolled，including 35 Burkitt lymphoma, 18 diffused large B cell lymphoma/high-grade B cell lymphoma (DLBCL/HGBCL). We collected 38 tissue and 124 plasma samples for somatic mutation testing. The number of somatic mutations and the TOP 5 genes detected in the 38 tissues and 31 baseline plasma samples, were 416 vs 496, and MYC(71%), DDX3X(45%)，ID3 (42%), TP53(40%), SMARCA4(29%) (Fig1. A)vs MYC(52%), DDX3X(45%)，ID3(42%), TP53(36%), GNA13(23%) (Fig1. B), respectively. The median allele frequency of mutations in plasma was 3%(ranged from 0.2% to 96.6%) and MYC, DDX3X, ID3, TP53, SMARCA4,ARID1A shows higher max somatic allele frequency (MSAF), indicated that was the early events in tumor genesis. The sensitivity of plasma ctDNA to detecting tissue mutations was 63.4% in the 19 matched samples (11 samples from BL and 8 samples from DLBCL/HGBCL) and the sensitivity in BL and DLBCL/HGBCL were 64.1% and 62%, respectively. All genomic alteration types, including single nucleotide variants (SNVs), indels, and gene fusions were detected in similar proportions in each sample type and the gene mutation rate of every gene detected in paired tissue and ctDNA samples. Among the 37 mature B-NHL patients, 6 patients were collected plasma samples after resection of tumor, of which 4 patients was not detected the somatic gene mutations in plasma (Fig. 2). The abundance of ctDNA in patients with stage IV (N=10) was significantly higher than that of stage I-II (N=6) (P=0.0002) and stage III patients(N=15)(P<0.0001)(Fig3. A). Similarly the abundance of ctDNA mutations in high risk patients(N =11)was significantly higher than that of low risk patients (N=8)(P<0.0001) and Medium risk patients (N=12) (P<0.0001) (Fig3. B). MSAF of ctDNA mutations was significantly correlated with LDH and the abundance of ctDNA mutations (P<0.0001) (Fig3. C,D). With a median follow-up of 182 Days, 33 patients have completed anti-tumor treatment, 27 patients completed post-treatment PET-CT, and 20 patients have done ctDNA testing synchronously. PET-CT showed tumor residue in 4 patients, of which 2 patients showed no tumor residue in pathology and ctDNA, 1 patient showed tumor residue in pathology but not in ctDNA and with tumor progression 6 months after treatment, 1 patient unable to take biopsy showed no tumor residue in ctDNA and was no tumor reccourence with regular follow-up. At the last follow-up, 1 patient was disease progression, and all of the 53 patients survived. Conclusion Plasma ctDNA testing by NGS was practicable in pediatric mature B-NHL. The abundance of ctDNA is significantly related to tumor burden. CtDNA testing may be more sensitive than PET-CT for residual disease assessment. Nevertheless, sample size expansion is required to verify such conclusions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

ITVT-05. Intraoperative Ultrasound Guidance Improves Resection In Gliomas – Results From A Single Centre Propensity Matched Comparative Cohort Analysis Of 2D Vs Navigated 3D Ultrasound In 500 Gliomas

INTRODUCTION Intraoperative ultrasound (iUS) is a promising tool for glioma surgery. Navigated 3-D (n3D) iUS has many benefits over standard 2-D iUS. METHODS This was a retrospective comparative cohort study using propensity score matching (PSM). 500 consecutive histologically confirmed gliomas were divided into 2 cohorts – 2DiUS - Cohort A; and n3DiUS -Cohort B. PSM was used to account for known confounders (250 in each group; 1:1 matching). Gross total resection rates (based on iUS findings as well as postoperative MR) and perioperative morbidity were analyzed across the groups as were factors influencing these outcomes (using univariate as well as multivariate regression models). RESULTS Overall, the majority of the patients were adults (94%), males (71%) with hemispheric tumors (96%). 35% had tumors close to eloquent regions and 23% had received some prior treatment. The majority were high-grade gliomas (85%). 2D iUS was employed mainly for localization (80%) whereas n3D was used predominantly for resection control (84%) [p < 0.001]. GTR rate was higher in the n3D cohort (55.2% vs 38.4% in 2D; p = 0.001). The odds of having a complete resection in the n3D cohort was twice that of the 2D. Prior treatment, hemispheric location, and use of fluorescence were also significantly associated with higher GTR rates on univariate analysis. On multivariate analysis, all of these remained significant. There was no difference in the morbidity rates in the two cohorts. N3D iUS had a higher specificity and positive likelihood ratio in detecting tumor residue. CONCLUSION For hemispheric gliomas undergoing resective surgery, the use of navigated 3D ultrasound improves GTR rates, with no added morbidity. It is more likely to be used for resection control mode than is 2DUS and this is probably because n3DUS is more specific and likely to pick up tumor residues contributing to its better accuracy.

Radiofrequency ablation combined with transarterial chemoembolization in treatment of hepatocellular carcinoma adjacent to the second hepatic hilus

Purpose To explore the efficacy and safety of using radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) adjacent to the second hepatic hilus. Methods Between February 2011 and June 2013, 17 patients with HCC underwent combination therapy of TACE and RFA under DSA and CT guidance at our institution. The 17 patients had a total of 23 hepatic tumors, 17 of which were adjacent to the second hepatic hilus. Results TACE combined with RFA was performed successfully in all 17 patients with no mortalities or major morbidities. During the 1-month follow-up, tumors of 15 patients (88.2%) were completely ablated after one therapy session and 2 patients had detectable tumor residue. During the follow-up time period (range 6–52 months), local tumor progression developed in 1 patient (1/17, 5.9%) and both local tumor progression and new tumors appeared in 1 patient (1/17, 5.9%). Also, new tumors developed in the untreated portions of the liver in 8 patients (8/17, 47.1%). No distant metastasis was found. Of the 17 patients, 6 (35.3%) died due to tumor progression (3/17, 17.6%), liver failure (2/17, 11.8%), or massive hemorrhage of the gastrointestinal tract (1/17, 5.9%). The overall survival rates were 94.1% (16/17), 82.4% (14/17), and 61.8% (11/17) at 12, 18, and 24 months, respectively, and the median survival time was 25 months (95% CI 18–27). Conclusion Treatment using combination of TACE and RFA is an effective and safe therapeutic strategy for treating HCC with tumor(s) adjacent to the second hepatic hilus.

Is Revision Surgery Necessary for Patients With High Risk of Recurrence After Parotidectomy? A Multicenter Retrospective Study

Objectives: Close margin is a frequent situation after parotidectomy. The need for systematic prophylactic revision surgery is a question that arises regularly for malignant tumors, as it exposes to a high risk of facial palsy, while oncological benefits are unclear. Study Design: retrospective study. Setting: Multicentric. Subjects and Methods: We included all patients operated for systematic revision surgery in case of close margins after parotidectomy for a malignant tumor and analyzed the rate of tumor residue and its risk factors. Results: A tumor residue was identified in 43.5% of 23 cases, but none in case of initial complete excision with supra-millimetric margins. Invaded lymph nodes were identified in 6 cases, but none in case of low-grade tumors. Conclusions: Systematic revision seems mandatory in case of infra-millimetric margins and high-grade tumors or positive lymph node; further studies are needed to confirm whether it can be spared for T1-T2/N0 low-grade tumors, with close margins but complete initial excision.

Successful Pregnancies in an Acromegalic Woman After Non-Radical Pituitary Adenomectomy for Somatoprolactinoma

Background: Pregnancy is unusual in patients with acromegaly due to somatotropinomas or somatoprolactinomas. Fertility is impaired because of hormonal hypersecretion, pituitary damage by tumor compression or both. Managing somatoprolactinomas and fertility issues are often challenging. Clinical Case: A 20-year woman with primary amenorrhea and headache was diagnosed with hypogonadotrophic hypogonadism secondary to hyperprolactinemia (2500 µg/L, n<23 µg/L). No other abnormalities were found on the pituitary function screening tests. MRI revealed an intra and suprasellar adenoma (2.5x1.8x1.8 cm) with optic chiasm compression. The onset of menses occurred after 11 months under dopaminergic treatment, and tumor size diminished (1.9x1.5x1.5 cm), bringing on optic chiasm decompression. She remained under dopamine agonist treatment for 6 years, when she realized extremities enlargement and height increase by 3 cm. Acromegaly was confirmed by blood levels of IGF-1 (3.37xULN), GH (8 µg/L, n<8 µg/L), and GH nadir (4.3 µg/L, n<1 µg/L) during OGTT. Then, octreotide LAR was added to cabergoline treatment while waiting for elective surgical treatment. She underwent to transsphenoidal endonasal neurosurgical microscopy approach guided by neuronavigation, with the removal of a large portion of tumor. However, it was not possible to extract the part of invasive adenoma close to right carotid artery due to the risk of vascular and intracavernous cranial nerves injury. Immunohistochemistry analysis of the adenoma was positive only for GH cells with low Ki67 index (<1%). Due to the poor biochemical control (unsuppressed post-OGTT GH, IGF-1 1.66xULN and PRL 301 µg/L) and the presence of a small stable tumor residue, treatment with cabergoline and somatostatin analogues was maintained (3-year octreotide LAR, transitioned to lanreotide in an attempt to achieve a better biochemical response). After 14 years of the initial diagnosis and 5 years post-surgery, the patient expressed the desire to get pregnant and all medications in use were suspended. In the following 3 years, she had two uneventful gestation without complications or worsen of acromegaly; she only breastfed for few months after her first pregnancy. The second one was a twin pregnancy. After one year, the MRI revealed no increase of tumor mass (1.0x0.3x1.0 cm), and PRL levels withing normal range, IGF-1 slightly elevated, but GH not suppressed by OGTT. Cabergoline was reintroduced and the biochemical control of acromegaly was achieved. Conclusion: We reported the very unusual spontaneous conception and normal course of pregnancies in a woman with acromegaly, who was submitted to successful transsphenoidal neurosurgical microscopy approach in which large part of the tumor was removed and the normal pituitary tissue was preserved, allowing fertility restoration.

Intraoperative Ultrasound-Assisted Extent of Resection Assessment in Pediatric Neurosurgical Oncology

Central nervous system tumors represent the most frequent solid malignancy in the pediatric population. Maximal safe surgical resection is a mainstay of treatment, with significant prognostic impact for the majority of histotypes. Intraoperative ultrasound (ioUS) is a widely available tool in neurosurgery to assist in intracerebral disease resection. Despite technical caveats, preliminary experiences suggest a satisfactory predictive ability, when compared to magnetic resonance imaging (MRI) studies. Most of the available evidence on ioUS applications in brain tumors derive from adult series, a scenario that might not be representative of the pediatric population. We present our preliminary experience comparing ioUS-assisted resection assessment to early post-operative MRI findings in 154 consecutive brain tumor resections at our pediatric neurosurgical unit. A high concordance was observed between ioUS and post-operative MRI. Overall ioUS demonstrated a positive predictive value of 98%, a negative predictive value of 92% in assessing the presence of tumor residue compared to postoperative MRI. Overall, sensibility and specificity were 86% and 99%, respectively. On a multivariate analysis, the only variable significantly associated to unexpected tumor residue on postoperative MRI was histology. Tumor location, patient positioning during surgery, age and initial tumor volume were not significantly associated with ioUS predictive ability. Our data suggest a very good predictive value of ioUS in brain tumor resective procedures in children. Low-grade glioma, high-grade glioma and craniopharyngioma might represent a setting deserving specific endeavours in order to improve intraoperative extent of resection assessment ability.

Suboccipital Retrocondylar Approach for an Anterolateral Foramen Magnum Meningioma

Objectives This study was to demonstrate surgical technique for an anterolateral foramen magnum meningioma. Design Present study is presented through an operative video. Setting This study is conducted at the Department of Neurosurgery, Tîrgu Mureș, Romania. Participants A 62-year-old female is the participant who was diagnosed with a foramen magnum meningioma. Main Outcome Measures Complete surgical resection of the tumor with no postoperative deficits or complications. Results A 62 years-old female was admitted for left hemilingual atrophia, dysphonia, right hemiparesis grade 2 of 5, right hemihypesthesia, and cervical pain. The magnetic resonance imaging (MRI) showed a right foramen magnum meningioma, sized approximately 2 cm in all planes (Fig. 1). This was classified with the Bernard system as an intradural foramen magnum meningioma with anterolateral insertion to the dura mater and below the vertebral artery. A suboccipital, retrocondylar, and c1 right hemilaminectomy approach was performed. Using microsurgical tumoral decompression techniques, ultrasonic aspiration, and following the natural cleavage planes, complete tumor removal was achieved (Fig. 2). The patient presented an uneventful postoperative course with no postoperative new neurological deficits and was discharged at home 7 days following surgery. Control MRI at 6 months (Fig. 1) and 2 years showed no tumor residue or recurrence. Neurologic status at 6 months was excellent, showing complete remission of symptoms. Conclusion Retrocondylar suboccipital approach is a safe and feasible option for anterolateral foramen magnum meningiomas provided that natural corridors and dynamic retraction are used.The link to the video can be found at: https://youtu.be/jpxMcjCpN6E.

Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy

Aims: To investigate the predictive capacity of early post-treatment diffusion-weighted magnetic resonance imaging (MRI) for recurrence or tumor progression in patients with no tumor residue after chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma, and, to assess the predictive capacity of pre-treatment diffusion-weighted MRI for persistent tumor residue post-CRT. Materials and Method: A single center cohort study was performed in one French hospital. All patients with squamous cell carcinoma receiving CRT (no surgical indication) were included. Two diffusion-weighted MRI were performed: one within 8 days before CRT and one 3 months after completing CRT with determination of median tumor apparent diffusion coefficient (ADC). Main outcome: The primary endpoint was progression-free survival. Results: 59 patients were included prior to CRT and 46 (78.0%) completed CRT. A post-CRT tumor residue was found in 19/46 (41.3%) patients. In univariate analysis, initial ADC was significantly lower in patients with residue post CRT (0.56 ± 0.11 versus 0.79 ± 0.13; p < 0.001). When initial ADC was dichotomized at the median, initial ADC lower than 0.7 was significantly more frequent in patients with residue post CRT (73.7% versus 11.1%, p < 0.0001). In multivariate analysis, only initial ADC lower than 0.7 was significantly associated with tumor residue (OR = 22.6; IC [4.9–103.6], p < 0.0001). Among 26 patients without tumor residue after CRT and followed up until 12 months, 6 (23.1%) presented recurrence or progression. Only univariate analysis was performed due to a small number of events. The only factor significantly associated with disease progression or early recurrence was the delta ADC (p = 0.0009). When ADC variation was dichotomized at the median, patients with ADC variation greater than 0.7 had time of disease-free survival significantly longer than patients with ADC variation lower than 0.7 (377.5 [286–402] days versus 253 [198–370], p < 0.0001). Conclusion and relevance: Diffusion-weighted MRI could be a technique that enables differentiation of patients with high potential for early recurrence for whom intensive post-CRT monitoring is mandatory. Prospective studies with more inclusions would be necessary to validate our results.