Tissue Diagnosis Research Articles

The utility of [18F]Fluciclovine PET/CT in Evaluating Nonmetastatic Castrate-Resistant Prostate Cancer Patients (nmCRPCp): diagnostic performance and impact on management.

To evaluate the role of [18F]Fluciclovine PET/CT scan in restaging nmCRPCp and its impact on management. This retrospective study included all patients with nonmetastatic castrate-resistant prostate cancer, who underwent [18F]Fluciclovine PET/CT scans for restaging who had concern for disease progression. Two radiologists independently reviewed the PET/CT studies, assigned an overall impression, and reported the site and number of radiotracer activities in consensus and impact on management was recorded. Available tissue diagnosis and/or six-month clinical and imaging follow-up were used as reference standards. Thirty-five patients were included in this study. At least one lesion was detected in 73% (26/35) of the scans. Management changed in 71% (25/35) of patients, (22 positives and three negative scans). 26.9% (7/26) of patients were found to have an oligometastatic disease. Based on the reference standards, the diagnostic performance of [18F]Fluciclovine PET/CT in detecting recurrence in nmCRCP has 86%, sensitivity, 83% specificity, 96.1% PPV, and 55.5% NPV. There was no relationship between the Gleason score and a positive PET/CT scan in our patient population. Detecting the source of recurrence is challenging in nmCRCP patients when conventional imaging fails. Given the high PPV, sensitivity, and specificity, [18F]Fluciclovine PET/CT can be used instead of conventional imaging as a first-line choice due to its superiority over bone scan and added value of detecting soft tissue metastasis regardless of the initial Gleason score. The study highlights the added value of [18F]Fluciclovine PET/CT in detecting soft tissue metastasis regardless of the initial Gleason score, which is not possible with conventional imaging such as bone scans.The study highlights the potential role of [18F]Fluciclovine PET/CT guiding management change for nonmetastatic castrate-resistant prostate cancer patients, particularly those with oligometastatic disease.

Osseous and Myogenic Tumors of the Choroid

Myogenic and osseous tumors of the choroid are extremely rare clinical manifestations. The most common osseous choroidal tumor is choroidal osteoma, and the most common myogenic choroidal tumor is choroidal leiomyoma. Other common osseous lesions are listed as sclerochoroidal calcification and ossified choroidal hemangioma. It is of great importance to distinguish these lesions from malignant tumors, especially malignant melanoma. Multimodal imaging methods and tissue diagnosis with biopsy and immunohistochemical markers in myogenic tumors have an important place in the diagnosis. Although it is known that these lesions are systemically benign, they can threaten vision as a result of local mass effect and complications. Since some osseous tumors may accompany systemic metabolic disorders, systemic screening should be performed in necessary cases. Although rare, metastatic choroidal leiomyosarcoma cases have been described. In this case, it is important to diagnose the tumor quickly and accurately with a good anamnesis and tissue diagnosis, and to plan the appropriate treatment considering the sensitivity of the primary tumor.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression

Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.

Depigmentation of Melanin-containing Tissues Using Hypochlorous Acid to Enhance Hematoxylin-eosin and Immunohistochemical Staining.

Pathologists diagnose diseases by observing the histologic and cellular morphology microscopically. However, the high pigmentation in melanin-containing tumors can hide the tumor cell structures, making diagnosing challenging. Previously, hydrogen peroxide and potassium permanganate were utilized for melanin bleaching with several limitations. For instance, hydrogen peroxide has a weak bleaching ability, and the process is time-consuming (12 h). Meanwhile, potassium permanganate affects the antigenicity of antigens and is unsuitable for immunohistochemical (IHC) staining. In this study, the hypochlorous acid (HClO) solution was applied to hematoxylin-eosin and IHC staining of melanin tissue sections. The study discovered that 1% HClO could completely bleach melanin particles in tumor tissues in a short period (19.95 ± 2.53 min) without compromising the hematoxylin-eosin staining. In addition, 2% HClO was utilized for bleaching at room temperature for 61.17 ± 4.32 minutes after the tissue was incubated with 3,3'-diaminobenzidine in IHC staining. This treatment effectively removed melanin without negatively impacting 3,3'-diaminobenzidine signal expression, thus ensuring that the sections met the necessary diagnostic requirements. Therefore, this method could facilitate pathologists in disease diagnosis of melanin-containing tissues.

Automated Breast Ultrasound Provides Comparable Diagnostic Performance in Opportunistic Screening and Diagnostic Assessment

The aim of the work described here was to assess the performance of automated breast ultrasound (ABUS) as an adjunct to digital breast tomosynthesis (DBT) in the screening and diagnostic setting. This cross-sectional study of women who underwent DBT and ABUS from December 2019 to March 2022 included opportunistic and targeted screening cases, as well as symptomatic women. Breast density, Breast Imaging Reporting and Data System categories and histopathology reports were collected and compared. The PPV3 (proportion of examinations with abnormal findings that resulted in a tissue diagnosis of cancer), biopsy rate (percentage of biopsies performed) and cancer detection yield (number of malignancies found by the diagnostic test given to the study sample) were calculated. A total of 1089 ABUS examinations were performed (age range: 29-85 y, mean: 51.9 y). Among these were 909 screening (83.5%) and 180 diagnostic (16.5%) examinations. A total of 579 biopsies were performed on 407 patients, with a biopsy rate of 53.2%. There were 100 (9.2%) malignant lesions, 30 (5.2%) atypical/B3 lesions and 414 (71.5%) benign cases. In 9 cases (0.08%), ABUS alone detected malignancies, and in 19 cases (1.7%), DBT alone detected malignancies. The PPV3 in the screening group was 14.6%. ABUS is useful as an adjunct to DBT in the opportunistic screening and diagnostic setting.

Acoustic Radiation Force Impulse (ARFI) Elastography of Focal Splenic Lesions: Feasibility and Diagnostic Potential.

Nontraumatic focal splenic lesions (FSL) are rare, and the need for tissue diagnosis must be weighed against the very high risk of bleeding after a splenic biopsy. The aim of this study was to explore the feasibility and diagnostic potential of acoustic radiation force impulse (ARFI) elastography as a noninvasive method for different benign and malignant FSLs. No human studies on the elastographic characteristics of FSL exist. This was a retrospective analysis of 34 patients with FSLs, who underwent abdominal B-mode ultrasound (B-US), contrast-enhanced ultrasound (CEUS), and standardized ARFI examinations between October 2021 and December 2022 at our university hospital. The inclusion criteria were: (i) FSL size ≥ 1 cm; (ii) 10 valid ARFI measurements of the FSL, as well as of the normal splenic parenchyma (NSP) as an in vivo reference; and (iii) diagnostic confirmation of FSL etiology based on histological examination (8/34; 23.5%) or clinical evaluation, which included a clinical and sonographic follow-up (FU), CEUS morphology, and/or morphology on cross-sectional imaging (26/34; 76.5%). CEUS was performed on all patients and the FSLs were classified according to the current guidelines; cross-sectional imaging was available for 29/34 (85.3%). The mean FU duration was 25.8 ± 30.5 months. The mean ARFI velocity (MAV) of the FSL (MAVL), the NSP (MAVP), and the ratio of the MAVL to the MAVP (MAVL/P) were calculated and compared. Of the 34 FSLs, 13 (38.2%) were malignant (mFSL) and 21 (61.8%) were benign (bFSL). The MAVL of all 34 FSLs (2.74 ± 0.71 m/s) was lower than the MAVP (3.20 ± 0.59 m/s), p = 0.009, with a mean MAVL/P ratio of 0.90 ± 0.34. No significant differences in the MAVL were observed between the mFSL (2.66 ± 0.67 m/s) and bFSL (2.79 ± 0.75 m/s). There were also no significant differences between the MAVP in patients with mFSL (3.24 ± 0.68 m/s) as compared to that in the patients with bFSL (3.18 ± 0.55 m/s). Likewise, the MAV L/P ratio did not differ between the mFSL (0.90 ± 0.41 m/s) and bFSL (0.90 ± 0.30 m/s) groups. ARFI elastography is feasible in evaluating the stiffness of FSLs. The lesions' stiffness was lower than that of the NSP, regardless of the FSL etiology. However, differentiation between benign and malignant FSL with the help of this elastographic method does not appear possible. Larger prospective studies are needed to validate these findings.

Surgical management of craniocervical junction tuberculosis with atlanto-axial dislocation – A case report and review of the literature

Background: There are few guidelines on how to best manage craniovertebral junction (CVJ) tuberculosis (TB). Certainly, timely tissue diagnosis, immobilization of the neck, and decompression of CVJ with appropriate stabilization are the mainstays of treatment for TB at the CVJ. Case Description: Three patients, ages 16–68, presented with CVJ TB with atlanto-axial dislocation responsible for progressive quadriparesis/plegia. Based on X-rays, magnetic resonance, and computed tomography studies, patients underwent timely decompressions and fusions followed by antitubercular drug treatment. Conclusion: Early diagnosis, proper decompression with fusion, treated with anti-TB drug for proper period were keys to managing TB involving the craniocervical junction in these three patients.

SAT487 A Case of Mistaken Identity: A Rare Presentation of Ectopic Thyroid Tissue

Abstract Disclosure: N. Doshi: None. R. Azimzade: None. A. Rajpal: None. Background: Ectopic thyroid tissue (ETT) lateral to the midline is very rare, and its presence at the carotid bifurcation is exceedingly unique. Paraganglioma is the most common primary tumor at the carotid bifurcation, often called a carotid body tumor. We hereby present a case of lateral ETT with radiological features similar to paraganglioma. Case Description: A 72-year-old female with history of GERD was referred to us for evaluation of a well-circumscribed, slightly tender left neck mass. She has had the mass for approximately 15 years with previous evaluation with ultrasound in Yemen, where she was told to undergo surgery to remove it. She did not pursue surgery at that time. She moved to the U.S. one year ago and was re-evaluated for the neck mass. On examination, a firm mass was noted on the left side of the neck, followed by an ultrasound which demonstrated a 4.5 cm mass at the left carotid bifurcation and an enlarged right thyroid lobe of the same echogenicity with no tissue in the left thyroid bed. She had no clinical symptoms suggesting of hypo or hyperthyroidism. Laboratory examination showed suppressed TSH with elevated T3 suggesting thyrotoxicosis. CT neck was obtained for further characterization of the left neck mass which showed a hyper-enhancing, lobular soft tissue mass at the carotid bifurcation extending from the mandible to the level of the thyroid isthmus, concerning for carotid body paraganglioma or schwannoma. An I-123 scan demonstrated 24% (increased) uptake in the right thyroid lobe and minimal uptake in the carotid bifurcation tissue. The patient is currently being treated medically for thyrotoxicosis. Based on its ultrasonographic appearance, mild uptake on the I-123 scan, and no clinical suggestion of paraganglioma, the left neck mass is presumed to be ETT and no surgical intervention is being pursued. It is possible that the right lobe is thyrotoxic, suppressing iodine uptake in the ectopic tissue. Conclusion: This case demonstrates a unique presentation of ETT in the left carotid bifurcation with a thyrotoxic right lobe. It is difficult to distinguish the precise composition of neck masses at the carotid bifurcation, which has important implications for management. Often, an official diagnosis of thyroid tissue is made with histopathology only after the mass is surgically excised. Most ETT is benign in nature, and many times it is the only thyroid tissue available, thus surgery is not indicated. It is especially difficult to distinguish between ETT and paraganglioma on imaging itself. Somatostatin receptor scintigraphy, Ga-68/PET scanning, or iodine uptake scan can be useful to distinguish ETT from paraganglioma. Despite its rarity, lateral ETT must be included in the differential diagnosis of carotid body paraganglioma. Presentation Date: Saturday, June 17, 2023

Spectrum changes of pulsed chirped Generalized Hermite cosh-Gaussian beam through turbulent biological tissues

The main objective of this study is to investigate the development of the spectral intensity profile of a pulsed chirped Generalized Hermite cosh Gaussian (GHCG) beam through turbulent biological tissues. This is achieved using Schmitt's model for the power spectrum refractive index, the extended Huygens-Fresnel integral, and the Fourier Transform method. Graphical representations need to be generated to explore the effects of beam parameters and biological turbulence parameters on the considered beam. Furthermore, a thorough discussion is conducted to examine the influence of both optical parameters and biological tissue characteristics on spectral shifts at various observation positions. The findings hold potential applications in image recognition, medical devices, and the noninvasive optical diagnosis of biological tissue.

Use of artificial intelligence in the diagnosis, treatment and surveillance of patients with kidney cancer

Currently, artificial intelligence (AI) has developed greatly and has become the subject of active discussions. This is because artificial intelligence systems are constantly being improved by expanding their computing capabilities, as well as obtaining massive data. Due to this, AI can help to set a diagnosis and select the most effective treatment. The study aimed to analyse the possibilities of AI in the diagnosis, treatment and monitoring of patients with renal cell carcinoma (RCC). AI shows great prospects in the diagnosis urinary system lesions, in the ability to differentiate benign and malignant neoplasm (due to machine learning systems), as well as in predicting the histological subtype of the tumor. AI can be used at the intraoperative stage (thanks to the integration of virtual 3D models during surgical interventions), which reduces the frequency of thermal ischemia and damage to the kidney cavity system. AI finds its application in histopathological evaluation: the AI model reaches 100.0% sensitivity and 97.1% specificity in the differential diagnosis of normal tissue from RCC. AI model algorithms may be used to identify patients at high risk of relapse requiring long-term follow-up, as well as to develop individual treatment and follow-up strategies. All the above proves the possibility of using AI in all stages of the management of patients with RCC. The implementation of AI in medical practise opens new perspectives for the interpretation and understanding of complex data inaccessible to clinicians.

Impact of Waiting Times on Mortality in Advanced Stage Non-Small Cell Lung Cancer: A 10-Year Retrospective Cohort Study in Thailand.

This study investigated the relationship between mortality and waiting times from diagnosis to first treatment while also considering other important risk factors associated with mortality. This is a cohort study including 497 patients diagnosed with advanced stage non-small cell lung cancer (NSCLC) between 1st January 2012 and 31st December 2021. The risk factors and waiting periods were analysed to determine their association with mortality. The waiting periods were recorded based on the timeline of patient visits, including the time between the 1st visit and imaging, the time between the 1st visit and tissue diagnosis, the time between the procedure and tissue diagnosis, the time between tissue diagnosis and treatment and the time from the 1st visit until treatment. The data were assessed using Cox regression with time-varying covariates. Waiting time for tissue diagnosis had a modest effect on mortality, a waiting time of more than four weeks indicated poor prognosis both in univariate and multivariate analyses [HR 1.48 (95%CI 1.18-1.87), p = < 0.01), adjusted HR 1.007 (95%CI 1.002-1.010), p = 0.02]. Waiting time for other services was not shown to be associated with mortality. The mortality rate was 3 times higher in patients with poor ECOG performance status than good ECOG performance [adjusted HR 3.17(2.04-4.91)]. Patients with EGFR sensitizing mutation who were treated with EGFR TKI therapy had a lower risk of lung cancer death compared to those being treated with chemotherapy [adjusted HR 0.49 (0.33-0.72)]. Molecular testing for EGFR sensitizing mutation and the TKI treatment were fundamental changes that assisted in improving survival rates for patients diagnosed with advanced stage lung cancer over the 10-year period. However, poor ECOG performance status remained a strong risk factor for lung cancer death. Longer waiting time for tissue diagnosis might indicate a poor prognosis.

Extended resections in the treatment of locally advanced lung cancer

Background: This study aims to evaluate surgical outcomes and prognosis in patients who underwent extended lung resection for locally advanced lung cancer. Methods: Between January 2015 and December 2019, a total of 61 patients (60 males, 1 female; mean age: 61.7±12.2 years; range, 32 to 90 years) with locally advanced non-small-cell lung cancer who underwent extended lung resection were retrospectively analyzed. Data including age, sex, comorbid diseases, symptoms, smoking status, pulmonary function test results, tumor location, methods used for preoperative tissue diagnosis, histopathological cell type, type of surgical resection, pathological stage, nodal involvement, postoperative complications, types of adjuvant therapy, and mortality rate were recorded. Survival and the factors affecting survival were examined. Results: Seven (11.4%) patients had Stage IIIB, 40 (65.5%) patients had Stage IIIA, and 14 (22.9%) patients had Stage IB disease. Intrapericardial pneumonectomy accounted for 30 (49.1%) of all extended lung resections. Chemotherapy was administered to 31 (50.8%) patients and chemoradiotherapy to 24 (39.3%) patients in the postoperative period. In the survival analysis, 70-month survival rate was calculated as 63.9% and the median survival was 48 months. There was a statistically significant association between survival with adjuvant chemotherapy and chemoradiotherapy (p=0.003). The mortality rate at 70 months of follow-up was 36.1%. Conclusion: Extended lung resection contributes significantly to the improvement of survival rates in carefully selected locally advanced cases. Particularly with adjuvant chemotherapy, local recurrences can be prevented, and survival rates can be improved.

Immunohistochemical expression of SOX2 in OKC and ameloblastoma: A comparative study.

Odontogenic, non-inflammatory maxillofacial cysts and tumours vary greatly in their ability to grow and cause local tissue destruction. Despite their common embryologic origin, the biologic mechanisms responsible for this diverse array of clinical behaviour are largely unknown. Unfortunately, even with accurate tissue diagnosis and appropriate surgical management, these tumours have relatively high recurrence rates. While this may be related to surgical technique, it may also be due to intrinsic tumour biology. SOX2 is differentially expressed in odontogenic cysts and tumours, which has an impact over patient prognosis. This could be related to their diverse cells of origin or stages of histogenesis. SOX2 is expressed in OKC and ameloblastoma, and in this study, we look forward to find altered levels and intensity of SOX2 in the above-mentioned lesions. To profile the expression of SOX2 in odontogenic keratocyst (OKC) and ameloblastomaTo compare the intensity of these lesions, analyse their intrinsic feature and predict their recurrence. Histopathologically diagnosed cases of OKC and ameloblastoma will be selected (n = 40). Paraffin-embedded, formalin-fixed sections of these lesions will be stained for SOX2 marker using a standard immunohistochemical technique. Positive control will be taken as oral squamous cell carcinoma and negative control will be taken as normal oral mucosa. A comparison between the stained cell types in odontogenic keratocyst and ameloblastoma revealed statistically significant differences. The immunoreactivity scores of SOX2 were analysed in both groups. The results indicated that 45% of OKC cases exhibited strongly positive reactivity, while 65% of ameloblastoma cases were negative. Statistical analysis demonstrated highly significant differences in the frequency of SOX2 expression between the two groups, with a higher frequency of negative expression in ameloblastoma. Stem cell markers have been observed in these lesions, suggesting the acquisition of stem-like properties by tumour cells, which can affect patient prognosis. Specifically, the marker SOX2 shows differential expression in odontogenic cysts and tumours. High expression of SOX2 in OKC indicates the presence of stem cells with significant self-renewal and proliferative properties, potentially signifying neoplastic behaviour. In contrast, weak or absent expression of SOX2 in ameloblastoma suggests different molecular pathways involved in its neoplastic behaviour.

The Role of Esophagography in the Diagnosis of Orthotopic Esophageal Squamous Cell Carcinoma in a Mouse Mode

Animal models play an irreplaceable role in pre-clinical studies of various tumors, mainly including xenogeneic/homograft subcutaneous tumor models. However, the subcutaneous transplanted tumor model is separated from the microenvironment of the primary tissue and fail to accurately simulate the growth of tumor cells in vivo. Therefore, orthotopic tumor models play an increasingly important role. For esophageal squamous cell carcinoma, chemotherapy-induced methods have successfully established mouse models of esophageal squamous cell carcinoma, but past experiments have found that it is still a challenge to confirm the success of the mouse model of esophageal cancer. The pathological diagnosis of the esophageal cancer tissue obtained from the killed mouse model remains the gold standard, but it also represents a lost opportunity to evaluate the efficacy of subsequent treatment. Notedly, esophagography is the primary examination for clinical patients with esophageal cancer. Therefore, the aim of this study is to evaluate whether esophagography can be used to establish a successful in situ mouse model of esophageal cancer. Referring to previous literature, we used the chemical drug 4-Nitroquinoline N-oxide (4-NQO) to induce orthotopic tumor model: A certain amount of 4-NQO was dissolved in propylene glycol to make a 2% stock solution, and then dissolved in 200ml of sterile water for the daily drinking water of mice. The water was kept in the dark and replaced once a week. After 16 weeks of induction, the drinking water was replaced by the same volume of sterile water and continued to be fed for 12 weeks. The mice were subsequently subjected to esophagography: First, the mice were fixed on a plastic plate, and the gavage needle was slowly inserted into the stomach, then slowly withdrawn out and gradually injected with meglumine diphosphate, with a total amount of 0.1-0.2ml. Then the radiolucent film was taken immediately, and three positions were selected, including the plain film, the standing film and the lateral film. After that, the mice were sacrificed and the esophagus of the mice was isolated and embedded in sections for pathological and immunohistochemical diagnosis. Finally, the results were compared with the imaging results. Based on the comparison of imaging and pathological results, we found that most of the esophageal segments with filling defects on esophagography were pathologically diagnosed as esophageal squamous cell carcinoma, and another part were diagnosed as esophageal papilloma. Compared with CT and MRI, esophagography has the advantages of simple operation and less consumable materials. We found that esophagography is a new non-invasive auxiliary diagnostic method for the successful establishment of an orthotopic mouse model of esophageal squamous cell carcinoma.

Automated Urinary Chemokine Assays for Noninvasive Detection of Kidney Transplant Rejection: A Prospective Cohort Study

Prior studies have demonstrated the diagnostic potential of urinary chemokines C-X-C motif ligand 9 (CXCL9) and CXCL10 for kidney transplant rejection. However, their benefit in addition to clinical information has not been demonstrated. We evaluated the diagnostic performance for detecting acute rejection of urinary CXCL9 and CXCL10 when integrated with clinical information. Single-center prospective cohort study. We analyzed 1,559 biopsy-paired urinary samples from 622 kidney transplants performed between April 2013 and July 2019 at a single transplant center in Belgium. External validation was performed in 986 biopsy-paired urinary samples. We quantified urinary CXCL9 (uCXCL9) and CXCL10 (uCXCL10) using an automated immunoassay platform and normalized the values to urinary creatinine. Urinary chemokines were incorporated into a multivariable model with routine clinical markers (estimated glomerular filtration rate, donor-specific antibodies, and polyoma viremia) (integrated model). This model was then compared with the tissue diagnosis according to the Banff classification for acute rejection. Acute rejection detected on kidney biopsy using the Banff classification. Chemokines integrated with routine clinical markers had high diagnostic value for detection of acute rejection (n=150) (receiver operating characteristic area under the curve 81.3% [95% CI, 77.6-85.0]). The integrated model would help avoid 59 protocol biopsies per 100 patients when the risk for rejection is predicted to be below 10%. The performance of the integrated model was similar in the external validation cohort. The cross-sectional nature obviates investigating the evolution over time and prediction of future rejection. The use of an integrated model of urinary chemokines and clinical markers for noninvasive monitoring of rejection could enable a reduction in the number of biopsies. Urinary chemokines may be useful noninvasive biomarkers whose use should be further studied in prospective randomized trials to clarify their role in guiding clinical care and the use of biopsies to detect rejection after kidney transplantation. Urinary chemokines CXCL9 and CXCL10 have been suggested to be good noninvasive biomarkers of kidney transplant rejection. However, defining a context of use and integration with clinical information is necessary before clinical implementation can begin. In this study, we demonstrated that urinary chemokines CXCL9 and CXCL10, together with clinical information, have substantial diagnostic accuracy for the detection of acute kidney transplant rejection. Application of urinary chemokines together with clinical information may guide biopsy practices following kidney transplantation and potentially reduce the need for kidney transplant biopsies.

A Journey from Schizophrenia to Paraneoplastic Limbic Encephalitis

A 58-year female presented with behavioral changes, dementia, and hallucinations for which she was initially treated as a case of schizophrenia. Later she developed hypersomnolence, speech difficulty and urinary incontinence. She also developed seizures later. On investigations cerebrospinal fluid (CSF) cell count was high and chest x-ray revealed homogeneous opacity over the left upper and midzone. Contrast-enhanced computerized tomography (CECT) Thorax revealed apical segment collapse consolidation with air bronchogram and bilateral pleural effusion. Multiple hepatic and bony metastasis s/o primary bronchoalveolar carcinoma. Osteolytic lesions were also found on skull x-ray and on pelvis x-ray. Tissue diagnosis couldn’t be done as the patient’s general condition deteriorated and the patient left against medical advice. From the above clinical picture and investigation findings, it was diagnosed as a case of paraneoplastic limbic encephalitis.

B-199 Performance of the MasSpec Pen for Intraoperative Margin Evaluation During Breast Conserving Surgeries

Abstract Background Breast cancer is the second leading cause of cancer deaths among females worldwide. Surgical resection is the most common treatment option for women diagnosed with breast cancers. Many women with in situ disease or early invasive breast cancer are candidates for breast conserving surgery (BCS), which involves removing the lesion of interest and preserving the rest of the breast. One of the greatest challenges a breast cancer surgeon faces is to achieve negative margins while optimizing aesthetic outcomes. Negative margins are highly desirable as they offer the greatest potential for prolonged disease-free survival. Accurate intraoperative surgical margin evaluation is therefore critical during BSC. Molecular technologies offer the opportunity to incorporate cancer-specific biomarkers into clinical decision-making for improved cancer detection. Our team has reported the development of an innovative handheld mass spectrometry (MS) probe, the MasSpec Pen (MSPen), for rapid and gentle molecular analysis of human tissues, including breast cancer tissues. The MSPen uses water to gently extract molecules from tissues upon contact, which are then analyzed by MS and statistical classifiers to provide a predictive classification within seconds. Here, we evaluate the performance of the MSPen for intraoperative detection of breast cancer. Methods The MSPen coupled to an Orbitrap Exploris 120 (Thermo Scientific) is being used to analyze both normal breast and invasive lobular carcinoma (ILC) banked tissues. Tissue samples are first thawed prior to analysis. After analysis, the region analyzed is demarcated, and the samples snap-frozen, sectioned, H&amp;E stained, following evaluation by a pathologist. We will then apply the least absolute shrinkage and selector operator (lasso) method to build classification models for distinguishing normal breast and ILC using the histologically validated mass spectra. The MSPen system is also implemented in the operating room for testing within surgical workflow. Analyses will be carried out during BCS surgeries for patients with ILC. The ILC classifier generated from banked tissues will be used to predict on data obtained from the intraoperative analyses and validated against final histopathological reports. Results To date, we have analyzed 213 banked human breast tissues using the MSPen, including healthy breast (n = 79), invasive ductal carcinoma (IDC) (n = 64), healthy lymph nodes (n = 26), and lymph nodes with metastatic IDC (n = 44). The rich mass spectral data obtained from breast tissues showed high relative abundance of various metabolites and lipid species that have been previously described as potentially diagnostic of breast cancer. Using this data, we built classifiers that discriminate cancer and normal breast tissues with high accuracy (overall 94%) for primary breast IDC. In a pilot clinical study, we demonstrated feasibility for ex vivo and in vivo tissue analysis using the MSPen platform during 29 breast surgeries. We are currently expanding our study to detect ILC using banked tissues and in patient tissues intraoperatively. Conclusion Our study in breast cancer provides evidence that the MSPen enables molecular-based diagnosis of IDC tissues using excised specimens and in in vivo and ex vivo analysis performed by surgeons intraoperatively. Current effort including ILC is expected to show similar capabilities for patients with ILC.

A retrospective comparative study on the diagnostic efficacy and the complications: between CassiII rotational core biopsy and core needle biopsy.

Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p<.001), 90.77% (kappa, 0.812; p<.001), 69.62% (kappa, 0.482; p<.001), and 86.92% (kappa, 0.552; p<.001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma.

Existence of Classical Solutions for a Class of the Khokhlov-Zabolotskaya-Kuznetsov Type Equations

In medical sciences, during medical exploration and diagnosis of tissues or in medical imaging, we often use mathematical models to answer questions related to these examinations. Among these models, the nonlinear partial differential equation of the Khokhlov--Zabolotskaya--Kuznetsov type (abbreviated as the KZK equation) is of proven interest in ultrasound acoustics problems. This mathematical model describes the nonlinear propagation of a sound pulse of finite amplitude in a thermo-viscous medium. The equation is obtained by combining the conservation of mass equation, the conservation of momentum equation and the equations of state. It should be noted that for this equation little mathematical analysis is reserved. This equation takes into account three combined effects: the diffraction of the wave, the absorption of energy and the nonlinearity of the medium in which the wave propagates. KZK-type equation introduced in this paper is a modified version of the KZK model known in acoustics. We study a class of~the~Khokhlov--Zabolotskaya--Kuznetsov type equations for the existence of global classical solutions. We~give conditions under which the considered equations have at least one and at least two classical solutions. To prove our main results, we propose a new approach based on recent theoretical results.

Impact of Biopsy Attempts, Race, and Access on Time to Initiation of Treatment for Pancreatic Cancer

BackgroundBiopsy of suspected pancreatic cancer (PDAC) in surgical candidates is informative however not always necessary. Biopsies impact treatment options as histological diagnosis are presently required for neo-adjuvant therapy, but not surgical resection. We explored the impact of pursuing tissue diagnosis by endoscopic ultrasound (EUS) biopsy on time to treatment in patients with resectable and borderline resectable PDAC. MethodsA retrospective review of surgical patients with ultimately proven PDAC was performed (2011–2021). Milestone dates (cancer suspected, biopsy(ies), surgical or neo-adjuvant treatment) were collected. Mann–Whitney-Wilcoxon tests, Pearson’s chi-squared tests, Fisher’s exact tests, linear regressions, and Cox proportional hazard models were used for data analysis. ResultsAmong 131 resectable and 58 borderline resectable patients, the borderline resectable group underwent more biopsies (1.2 vs 0.7, p < 0.0001), were more likely to undergo biopsy at tertiary care centers (67.2% vs 30.5%, p < 0.0001), and trended toward longer time to treatment (49 vs 44 days, p = 0.070). Significant increases in days to treatment were seen in patients with Black race (29 days, p = 0.0002) and Medicare insurance (22 days, p = 0.038) and no biopsies at a tertiary care center (10 days, p = 0.039). After adjusting for covariates, additional biopsies significantly delayed treatment (1 biopsy: 21 days, p = 0.0001; 2 biopsies: 44 days, p < 0.0001; 3 biopsies: 68 days, p < 0.0001). ConclusionsEUS biopsy significantly impacts time between suspicion and treatment of PDAC. This may be exacerbated by clinical practices increasingly favoring neo-adjuvant therapy that necessitates biopsy-proven disease. Time to treatment may also be impacted by access to tertiary centers and racial disparities.