Tumor Locations Research Articles

Analysis of DNA and RNA Genomic Profiles from Phase-II Clinical Trial NCT03398694 Showed Distinct Transcriptomic Profile for Patients With Local Failure

INTRODUCTION: Stereotactic radiosurgery (SRS) has become a standard of care for brain metastasis (BM). In the setting of lesions needing surgical intervention, it is typically delivered to the resection cavity after surgical resection to strike a balance between adverse effect from the dose of radiation and tumor recurrence. Pre-operative SRS is now being examined because of its ability to deliver radiation to all cells before surgical disruption and dispersion with added advantage of treating larger lesions with radiation. METHODS: We designed a phase II trial for patients with up to 4 BM and at least one resectable lesion. All lesions were treated with SRS and symptomatic lesions were resected. We examined both the clinical and biological outcomes. RESULTS: We performed whole genome DNA and RNA sequencing of the center and periphery of the resected lesion from the first 35 patients. We found that SRS causes significant and biologically observable damage to the tumor. Radiation induced DNA damage is qualitatively different between center and periphery of the tumor. Functionally distinct genetic profiles exist between both center and peripheral tumor locations as well as between different primary tumor types. Center of the tumor has higher functional mutation burden while peripheral samples initiate DNA repair pathways. Peripheral samples may interact more with surrounding environment when compared to central samples. Different radiation delivery modality has differential transcriptomic profile and patients who failed locally also had a distinct transcriptomic profile. CONCLUSIONS: In conclusion, radiation dosing fall-off has differential effect on the genomic landscape of the tumor and cells from the periphery are most likely gaining DNA repair abilities and that might explain tumor recurrence. Also, Gamma knife and LINAC as different genomic signature.

CASE REPORT : A RARE CASE OF CUTANEOUS DESMOID-TYPE FIBROMATOSIS

Desmoid fibromatosis (DF) is a rare, locally aggressive connective tissue malignancy primarily affecting musculoaponeurotic tissues, representing less than 3% of all neoplasms. This case report presents a 30-year-old male with cutaneous desmoid fibromatosis, a rare variant characterized by a painless, firm mass in the left shoulder region. Histopathological, immunohistochemical, and molecular analyses confirmed the diagnosis of desmoid cutaneous fibromatosis, with positive findings for nuclear beta-catenin. Management involved a multidisciplinary approach, with a conservative strategy due to the tumors size and location, emphasizing regular monitoring for recurrence. Differential diagnosis considerations included dermatomyofibroma and scar tissue. Treatment options for DF vary, with a shift towards observation as the primary strategy, particularly in cases where surgery may result in significant functional impairment. Medical treatment or surgery may be considered in symptomatic or progressive cases. Close surveillance and follow-up imaging are crucial for early detection of disease progression. cutaneous desmoid fibromatosis presents diagnostic challenges, highlighting the importance of early identification and biopsy to prevent misdiagnosis.

The Profile of Sinonasal Tumors with Orbital Involvement in Dr. M. Djamil General Hospital, Padang, Indonesia: A 10-Year Overview

Background: Sinonasal tumors are rare tumors, either malignant or benign, that vary greatly based on the origin and primary tumor location in the sinonasal tract. The close anatomical relationship between the sinonasal tract and the orbital cavity makes orbital involvement very common (50%-80%) in sinonasal tumors, and this indicates a negative prognostic factor in sinonasal malignancy. The purpose of this study is to demonstrate the profile of sinonasal tumors with orbital involvement in our center.
 Methods: Retrospective study from oncology subdivision files and medical records from January 2011 – December 2020. Collected data including age, gender, the clinical manifestations of orbital involvement, primary location, histopathology, and management of sinonasal tumors.
 Results: There were 35 patients examined by the oncology subdivision either directly came or consulted from the ENT department, consisting of 18 (51.4%) males and 17 (48.6%) females. The age of patients ranged from 11 to 83 years old. with the most common age groups being 41-50 and 51-60 (25.7% in each age group). The majority of the patients (77.1%) had presented with proptosis. Maxillary sinus was the most common (45.7%) primary site of tumors, and squamous cell carcinoma was the most common (51.4%) histopathology found. Most of the patients (37.1%) were treated with a combination of chemotherapy and radiotherapy.
 Conclusion: Orbital involvement commonly occurs in malignant sinonasal tumors with proptosis as a major clinical presentation. A combination of chemotherapy and radiotherapy was the most common practice management because the tumors were unresectable at the time of presentation.

Ependymomas of the spinal region in adults: Clinical and pathological features and MYCN expression levels in spinal ependymomas and myxopapillary ependymomas

BackgroundEpendymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal ependymoma (Sp-EPN), myxopapillary ependymoma (MPE), and Sp-EPN-MYCN amplified, each with distinct histopathological and molecular features. MethodsThis study investigated the clinical and pathological characteristics and MYCN expression levels of 35 Sp-EPN and MPE cases diagnosed at a tertiary university hospital over a decade-long period. ResultsTwenty-five cases were Sp-EPN and 10 cases were MPE, and were graded as WHO grade 2, except for 1 Sp-EPN case with grade 3 features. The most common symptoms were lower back pain and difficulty in walking. Radiology showed different tumor sizes and locations along the spinal cord, with MPEs exclusively in the lumbosacral region. Surgery was the main treatment, and gross total resection was achieved in all cases except for one. Immunohistochemistry showed low Ki-67 proliferation indices in all cases, and no MYCN expression. During follow-up, 3 (8.6 %) cases recurred and/or metastasized and 5 cases (14.3 %) died. No significant difference was found in disease-free survival or overall survival between Sp-EPN and MPE cases. However, 3 cases with grade 2 histology demonstrated recurrence and/or metastasis, despite the lack of MYCN expression. ConclusionOur results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.

Intraoperative mapping and preservation of executive functions in awake craniotomy: a systematic review.

Awake craniotomy (AC) allows intraoperative brain mapping (ioBM) for maximum lesion resection while monitoring and preserving neurological function. Conventionally, language, visuospatial assessment, and motor functions are mapped, while the assessment of executive functions (EF) is uncommon. Impaired EF may lead to occupational, personal, and social limitations, thus, a compromised quality of life. A comprehensive literature search was conducted through Scopus, Medline, and Cochrane Library using a pre-defined search strategy. Articles were selected after duplicate removal, initial screening, and full-text assessment. The demographic details, ioBM techniques, intraoperative tasks, and their assessments, the extent of resection (EOR), post-op EF and neurocognitive status, and feasibility and potential adverse effects of the procedure were reviewed. The correlations of tumor locations with intraoperative EF deficits were also assessed. A total of 13 studies with intraoperative EF assessment of 351 patients were reviewed. Awake-asleep-awake protocol was most commonly used. Most studies performed ioBM using bipolar stimulation, with a frequency of 60Hz, pulse durations ranging 1-2ms, and intensity ranging 2-6mA. Cognitive function was monitored with the Stroop task, spatial-2-back test, line-bisection test, trail-making-task, and digit-span tests. All studies reported similar or better EOR in patients with ioBM for EF. When comparing the neuropsychological outcomes of patients with ioBM of EF to those without it, all studies reported significantly better EF preservation in ioBM groups. Most authors reported EF mapping as a feasible tool to obtain satisfactory outcomes. Adverse effects included intraoperative seizures which were easily controlled. AC with ioBM of EF is a safe, effective, and feasible technique that allows satisfactory EOR and improved neurocognitive outcomes with minimal adverse effects.

Abstract 2393: Development of a novel implantable drug-eluting product for the local treatment of pancreatic adenocarcinoma

Abstract Background Local control of non-metastatic pancreatic ductal adenocarcinoma (PDAC) remains a major challenge. Therapies with reduced systemic toxicity are needed as intravenous (IV) infusions are limited by patient tolerance with only small amounts reaching the tumor. PanTher created PTM-101, a novel absorbable drug formulation containing paclitaxel, designed to be locally applied via minimally invasive surgery to provide chemotherapy precisely to the peritumoral area in PDAC. Methods A study was conducted using 3 cadaveric abdomens to evaluate surgical feasibility of delivering PTM-101 via laparoscopy. Prior to insertion of PTM-101 into the peritoneum, the surgeons prepared each product by suturing a 3-0 Vicryl SH (Ethicon) at four evenly spaced locations around the edge of the flat circular product. A periumbilical 10mm Hasson port was placed to insufflate the abdomen, followed by placement of 3 additional working ports (5mm). The liver capsule was carefully surveyed to exclude metastatic disease. The surgeons opened a window into the lesser sac through the greater omentum, lifting the stomach up from the transverse colon to expose the pancreas. PTM-101 (a 1mm thick and 6cm diameter film) was rolled into a tubular shape, inserted through the cannula, and affixed to the peri-pancreatic fat with existing vicryl stitches. Results The estimated total operative time from placement of the first trocar to removal of all equipment was 45 minutes, for the 3 procedures. The operations included 25 minutes for entry, port placement, exposure of the simulated pancreatic tumor location and 20 minutes to place and suture PTM-101. PTM-101 was easy to fit through the cannula and was sutured without difficulty to the peri-pancreatic fat that surrounds the capsule of the pancreas. To simulate a tumor with hepatic artery involvement, the implant was sutured towards the hepatoduodenal ligament in one specimen, near the area of the gastroduodenal artery takeoff, proper hepatic artery, and proximal portal vein. PTM-101 covered the entire head/neck area of the simulated tumor locations without requiring disruption of the tumor area or dissection of the tunnel under the pancreatic neck. Conclusion PTM-101 is flexible and conforms easily to the underlying topography, both in a concave (i.e., with the tumor intact) and convex (i.e., after resection) scenario. Although human anatomy does not allow for PTM-101 to completely wrap around the pancreas, the size and flexibility of the product enables it to “drape” over the edges covering areas near the superior mesenteric vein and artery (SMV/SMA). This placement could hypothetically increase the amount of drug reaching the area behind the pancreas to target tumors which abut or encase the mesoportal vasculature. A decrease in the tumor-vessel interface could downsize pancreatic tumors, with the goal of increasing resection rates and post-resection local control. Citation Format: Margaret Lashof-Sullivan, Leslie S. Sloan, Michael P. Kim, Laura Indolfi, Ching-Wei D. Tzeng. Development of a novel implantable drug-eluting product for the local treatment of pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2393.

Abstract 5068: Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study

Abstract Introduction: Clonal Hematopoiesis of indeterminate potential (CHIP) is a clonal expansion of mutations affecting genes involved in hematologic malignancies in patients without a hematological disease per se. It has emerged as a significant risk factor for cardiovascular events via skewing innate immune cells towards a pro-inflammatory state. Recently studies have shown its potential detrimental impact on overall survival in patients treated with chemotherapy. However, its impact on patients treated with immune checkpoint blockers in monotherapy remains unclear. Objective: Our aim is to evaluate CHIP prevalence in a prospective cohort of patients treated with ICB for advanced solid tumors and its impact on patient outcomes. Materials and methods: We performed a Next-Generation Sequencing (NGS) panel of 74-genes dedicated to hematological alterations on DNA extracted from whole blood collected before first administration of an ICB for an advanced solid tumor, within the PREMIS trial (NCT03984318). CHIP prevalence was assessed according to a variant allele frequency (VAF) threshold ≥ 2%. Results: We included 127 pts in the analysis; 88 pts (69%) were male with a median age of 70 years [range 37-100]. Most common tumor locations were skin (29%), genitourinary (25%) and lung (19%). ICB setting was 1°L in 40% of patients; 2°L in 43%; > 3°L in 17%, and the most used ICB was Nivolumab in 39% of patients. At least 1 CHIP mutation was found in 55 pts (43%). The most frequent mutations were found in DNMT3A (40%), TET2 (18%) and PPM1D (13%). Co-mutations were found in 20% of patients. Median PFS was 7.7 months (m) for CHIPm patients compared to 5.7 m in non-CHIPm patients (p=2.2) and median OS was 16.2 m in CHIPm patients compared to 14.9 m in non-CHIPm patients (p= .5). No pts developed hematological disease during the follow up. Conclusion: CHIP is commonly found in pts with solid tumors, with a prevalence in our cohort of 43% with no statistical significance neither in PFS nor in OS in the CHIP-mutated population. Citation Format: Julieta Elena Rodriguez, François Xavier Danlos, Alicia Larive, Aurelien Marabelle, Yohann Loriot, Caroline Robert, Laurence Albiges, Maxime Frelaut, Mihaela Aldea, Benjamin Besse, Michel Ducreux, Caroline Even, Jean Baptiste Micol, Santiago Ponce, Christophe Marzac, Nathalie Chaput, Christophe Massard, Capucine Baldini. Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5068.

Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training. To overcome this limitation, this study explores semi-supervised approaches utilizing unlabeled data, specifically focusing on PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) obtained from two centers. We considered 2-[18F]FDG PET images of 292 patients PMBCL (n = 104) and DLBCL (n = 188) (n = 232 for training and validation, and n = 60 for external testing). We harnessed classical wisdom embedded in traditional segmentation methods, such as the fuzzy clustering loss function (FCM), to tailor the training strategy for a 3D U-Net model, incorporating both supervised and unsupervised learning approaches. Various supervision levels were explored, including fully supervised methods with labeled FCM and unified focal/Dice loss, unsupervised methods with robust FCM (RFCM) and Mumford-Shah (MS) loss, and semi-supervised methods combining FCM with supervised Dice loss (MS + Dice) or labeled FCM (RFCM + FCM). The unified loss function yielded higher Dice scores (0.73 ± 0.11; 95% CI 0.67-0.8) than Dice loss (p value < 0.01). Among the semi-supervised approaches, RFCM + αFCM (α = 0.3) showed the best performance, with Dice score of 0.68 ± 0.10 (95% CI 0.45-0.77), outperforming MS + αDice for any supervision level (any α) (p < 0.01). Another semi-supervised approach with MS + αDice (α = 0.2) achieved Dice score of 0.59 ± 0.09 (95% CI 0.44-0.76) surpassing other supervision levels (p < 0.01). Given the time-consuming nature of manual delineations and the inconsistencies they may introduce, semi-supervised approaches hold promise for automating medical imaging segmentation workflows.

Added value of DCER-features to clinicopathologic model for predicting metachronous metastases in rectal cancer patients.

The study aimed to investigate whether dynamic contrast-enhanced MRI parameters and preoperative radiological features (DCER-Features) add value to the clinicopathologic model for predicting metachronous metastases in rectal cancer patients. From January 2014 to December 2020, 859 patients in the PACS system were retrospectively screened. Of the initial 722 patients with surgically confirmed rectal cancer and no synchronous metastases, 579 patients were excluded for various reasons such as lack of clinicopathological or radiological information. 143 patients were finally included in this study. And 73 Patients of them developed metachronous metastasis within five years. After stepwise multiple regression analyses, we constructed three distinct models. Model 1 was developed solely based on clinicopathological factors, and model 2 incorporated clinicopathological characteristics along with DCE-MRI parameters. Finally, model 3 was built on all available factors, including clinicopathological characteristics, DCE-MRI parameters, and radiological features based on rectal magnetic resonance imaging. The radiological features assessed in this study encompass tumor imaging staging, location, and circumferential resection margin (CRM) for primary tumors, as well as the number of visible lymph nodes and suspected metastatic lymph nodes. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were conducted to evaluate whether the diagnostic efficiency was improved. The performance of model 3 (including clinicopathologic characteristics and DCER-Features) was the best (AUC: 0.856, 95% CI 0.778-0.886), whereas it was 0.796 (95% CI 0.720-0.828) for model 2 and 0.709 (95% CI 0.612-0.778) for model 1 (DeLong test: model 1 vs model 2, p = 0.004; model 2 vs model 3, p = 0.037; model 1 vs model 3, p < 0.001). The decision curves indicated that the net benefit of model 3 was higher than the other two models at each referral threshold. The calibration plot of the three models revealed an excellent predictive accuracy. This study suggests that DCER-Features have added value for the clinicopathological model to predict metachronous metastasis in patients with rectal cancers.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer

BackgroundTo develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and MethodsIn this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. ResultsAxillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. ConclusionNomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Integral neuro-oncological diagnosis As the basis for personalized treatment Of brain tumors (on the example of gliomas In children)

Brain tumors are the most common group of neoplasms in children, which is in the top-3 causes of infant mortality from oncopathology. The aim of the study is to make a literature review of modern approaches to the personalization of treatment of CNS tumors in children based on the study of molecular genetics, immunohistochemical and imagingт characteristics. The article provides a description of the most common types of neoplasms of the nervous system — low grade gliomas (LGG), high grade gliomas (HGG), mixed glioneural tumors, etc. The molecular genetics, immunohistochemical, visualization characteristics of each type of gliomas are described. Modern information on prognosis and treatment of tumors is also given in the publication. The prognosis of the course of LGG/GNT in children depends more often on the patient’s age, histology, and location of the tumor, as well as its molecular profile. Older patients have a more favorable prognosis than younger children. Well-visualized tumors located superficially have a better outcome than diffuse gliomas, as well as deeply located tumors. Detection of BRAF mutations and FGFR rearrangements may indicate a better prognosis than in the presence of SNV. Local mutations of BRAF with concomitant deletion of CDKN2A, as well as mutations with H3.3 pK27 are the most dangerous.

Screening Implications for Distribution of Colorectal Cancer Subsite by Age and Role of Flexible Sigmoidoscopy.

Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000-2020). Tumors from the rectum to the descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors required colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, was assessed using the overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95% CI 2.03-2.16 age < 45, OR 2.20, 95% CI 2.13-2.27 age 45-49 versus age ≥ 50). Male sex (OR 1.54, 95% CI 1.51-1.56) and Asian or Pacific Islander race (OR 1.60, 95% CI 1.56-1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: 58% of CRC arises in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy.

Baseline shift corrections towards the heart: External validation of the impact on survival in early-stage NSCLC patients

PurposeTo externally validate Johnson-Hart et al. findings: the association of tumor baseline shifts towards the heart with overall survival (OS) in SBRT for NSCLC. Further analysis included investigating the presence of interfractional heart baseline shifts and the association of OS with heart dose change during treatment. MethodsData from 416 SBRT early-stage NSCLC patients was collected. Pearson’s correlations (PCCs) between clinical variables and treatment-averaged tumor shifts towards/away from the heart were explored. Validation of published multivariable Cox model was performed. PCCs between heart and tumor baseline shifts were analyzed. Dose accumulation was performed following daily CBCT-to-pCT deformable registration. Maximum heart dose (D0) was computed for planned and accumulated doses. Differences in OS according to shifts towards/away from the heart or D0 increase/decrease were analyzed. Significant D0 differences between patients with D0 increase/decrease and different tumor locations were explored. ResultsTumor shifts towards/away from the heart showed no significant association with OS (p = 0.91). Distance between PTV and heart correlated significantly (PCC = 0.18) with shifts to the heart. Cox model did not validate in our cohort. Heart presented baseline shifts positively correlated with tumor baseline shifts in all three directions (PCC ≥ 0.38; p < 0.001). Counterintuitively, patients experiencing increased D0 during treatment showed significantly better OS (p = 0.0077). Upper-lobe tumor patients with increased D0 had lower D0 than those with decreased D0 (right-upper-lobe p ≤ 0.018). ConclusionsIn our SBRT cohort, the shifts towards the heart were not associated with worse OS. Moderate correlations were found between tumor and heart baseline shifts in each direction. Moreover, the distance between the PTV and the heart showed a significant correlation with shifts to the heart.

Abstract A057: Inter-tumor heterogeneity revealed by multi-site whole genome sequencing of high grade serous ovarian cancer

Abstract A057: Inter-tumor heterogeneity revealed by multi-site whole genome sequencing of high grade serous ovarian cancer

Treatment Planning and Aberration Correction Algorithm for HIFU Ablation of Renal Tumors.

High-intensity focused ultrasound (HIFU) applications for thermal or mechanical ablation of renal tumors often encounter challenges due to significant beam aberration and refraction caused by oblique beam incidence, inhomogeneous tissue layers, and presence of gas and bones within the beam. These losses can be significantly mitigated through sonication geometry planning, patient positioning, and aberration correction using multielement phased arrays. Here, a sonication planning algorithm is introduced, which uses the simulations to select the optimal transducer position and evaluate the effect of aberrations and acoustic field quality at the target region after aberration correction. Optimization of transducer positioning is implemented using a graphical user interface (GUI) to visualize a segmented 3-D computed tomography (CT)-based acoustic model of the body and to select sonication geometry through a combination of manual and automated approaches. An HIFU array (1.5 MHz, 256 elements) and three renal cell carcinoma (RCC) cases with different tumor locations and patient body habitus were considered. After array positioning, the correction of aberrations was performed using a combination of backpropagation from the focus with an ordinary least squares (OLS) optimization of phases at the array elements. The forward propagation was simulated using a combination of the Rayleigh integral and k-space pseudospectral method (k-Wave toolbox). After correction, simulated HIFU fields showed tight focusing and up to threefold higher maximum pressure within the target region. The addition of OLS optimization to the aberration correction method yielded up to 30% higher maximum pressure compared to the conventional backpropagation and up to 250% higher maximum pressure compared to the ray-tracing method, particularly in strongly distorted cases.

Proximal Humerus Reconstruction for Bone Sarcomas: A Critical Analysis.

» The proximal humerus is a common location for primary bone tumors, and the goal of surgical care is to obtain a negative margin resection and subsequent reconstruction of the proximal humerus to allow for shoulder function.» The current evidence supports the use of reverse total shoulder arthroplasty over hemiarthroplasty when reconstructing the proximal humerus after resection of a bone sarcoma if the axillary nerve can be preserved.» There is a lack of high-quality data comparing allograft prosthetic composite (APC) with endoprosthetic reconstruction of the proximal humerus.» Reverse APC should be performed using an allograft with donor rotator cuff to allow for soft-tissue repair of the donor and host rotator cuff, leading to improvements in shoulder motion compared with an endoprosthesis.

Ultrasound principles and instrumentation

Ultrasound (US) is a fundamental and inexpensive tool both for the prompt diagnosis and for the study of diverse medical conditions. Its widespread use is partly due to the availability of US devices in the daily practice of physicians. US can be performed in real-time and is instrumental in the generation of clinical algorithms for the management of situations like trauma. It also constitutes a primary approach for the study of oncological diseases, and a guidance tool for interventions such as percutaneous drainages. In addition, and specifically for HPB surgeons, US is an essential tool in the operating room: intraoperative (either open or laparoscopic) US is necessary for the accurate determination of the stage, location, number, and margins of tumors within the liver, pancreas, or biliary tree. On another note, reading and understanding US images are skills that require time and training, which should be taught during surgical residencies. However, this is not customary in most residencies globally. This chapter offers a concise yet comprehensive elucidation of the basic principles of ultrasonography, the instruments required to perform an ultrasonic assessment of a patient, and the basic ultrasound controls.

Correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in the intermediate- and advanced-stage esophageal cancer.

Radiation therapy plays a pivotal role as the primary adjuvant treatment for esophageal cancer (EPC), emphasizing the critical importance of carefully balancing radiation doses to the target area and organs at risk in the radiotherapeutic management of esophageal cancer. This study aimed to explore the correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in intermediate- and advanced-stage esophagus cancer to provide a reference for clinical treatment. A total of 105 patients with intermediate- and advanced-stage EPC, who received treatment in our hospital from 2019 to 2021, were included. The morphological parameters were calculated by imaging. Intensity-modulated radiation therapy plan was executed at Raystation4.7. The PTV-G stood for the externally expanded planning target volume (PTV) of the gross tumor volume (GTV) and PTV-C for the externally expanded volume of the clinical target volume (CTV). The prescription dose of PTV-G and PTV-C was set as 60Gy/30F and 54Gy/30F, respectively. The linear regression model was used to analyze the correlation between morphologic parameters of EPC and dosimetric parameters of the heart and spinal cord. In 105 cases, the total lung length was correlated with the spinal cord maximum dose (D2 ). The heart mean doses (Dmean ) and heart V40 (the relative volume that receives 40 Gy or more) was correlated with PTV-G volume, PTV-G length; In middle- and upper-segment EPC cases, only the total lung volume was correlated with the spinal cord Dmean , spinal cord D2 , heart Dmean , and heart V40 ; In middle-stage EPC cases, the heart Dmean was correlated with the PTV-G volume, PTV-G length. The total lung length was correlated with the spinal cord D2 ; In middle- and lower-segment EPC, only the PTV-G volume and PTV-G length were correlated with the heart Dmean . All the aforementioned values were statistically significant. Combined with the unsegmented tumor and different locations, the organ at risk dose was comprehensively considered.

Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma.

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM's recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.

Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.