Successful Biopsy Research Articles

Repeat Sentinel Lymph Node Surgery in Recurrent Breast Cancer: Peritumoral vs. Periareolar Injections

BackgroundIn the setting of recurrent cancer, there is no standard methodology regarding the technical aspects of repeat sentinel lymph node (rSLN) surgery. We analyzed our institutional experience with attempted rSLN surgery to determine the optimal injection technique. Materials and MethodsSingle site, retrospective review of patients with prior lumpectomy for breast cancer who presented with recurrent or new ipsilateral breast cancer and underwent attempt at rSLN surgery from 2008 to 2017. Patients with prior mastectomy or no prior ipsilateral axillary operation were excluded. ResultsA total of 141 patients were included; 103 (73%) underwent successful rSLN biopsy procedure. Lymphoscintigraphy showed aberrant drainage in 32 (26%). Periareolar (PA) injection resulted in failed mapping in 23/99 (23%) and aberrant drainage in 25/85 (29%). By comparison, peritumoral (PT) injection had a 14/38 (37%) incidence of failed mapping and 7/37 (19%) aberrant drainage (P = .11 and .23, respectively). Of the patients with successful sentinel lymph node (SLN) biopsy procedure via PA injection, 11/76 (14%) were positive for metastatic disease as compared with 2/24 (8%) in PT injection. Sixteen patients had lymph node metastases; 13 (81%) were SLNs, including 3 positive aberrant SLNs. Five-year regional recurrence rates were 11.4% (95% confidence interval, 0%-21.5%) and 0% for PA and PT injection techniques, respectively. ConclusionPA and PT injections had a similar incidence of SLN identification and aberrant drainage. Preoperative lymphoscintigraphy is beneficial in patients with recurrent breast cancer given the higher incidence of aberrant drainage in this population. Patients who underwent PA injections had a higher incidence of regional recurrences but this difference was not statistically significant.

Abstract PS5-37: The feasibility of obtaining oncotype DX breast recurrence score® results from metastatic sites of patients with hormone receptor positive metastatic breast cancer

Abstract Background: Identifying when to start CDK4/6 inhibitors or use chemotherapy in hormone receptor positive (HR+) metastatic breast cancer (MBC) remains challenging. The 21-gene Oncotype DX Breast Recurrence Score® test is validated to predict chemotherapy benefit in early stage HR+ breast cancer but has not been studied for use in the MBC setting.Objective: To assess the feasibility of obtaining Recurrence Scores from metastatic sites after standard of care biopsy in HR+, HER2 negative patients and correlate Recurrence Score results from matched primary breast cancer when available. Methods: A total of 48 metastatic biopsies were retrieved retrospectively from the residual tissue of patients with primary HR+, HER2 negative breast cancer. This included 36 from bone and 12 from other sites [liver (7), lung (1), rectum (1), brain (1), skin (2)]. Slides were sent to Genomic Health Inc. for RNA isolation and Recurrence Score result determination using standardized protocols. Recurrence Score results were available for 18 matched primary and metastatic biopsy samples. The percent success rate for Recurrence Score result was determined for the various metastatic sites and results compared between matched primary and metastatic site. Results: Recurrence Score results were obtained in 48% of metastatic biopsies (23 of 48 samples) including bone (17), liver (4), lung (1), and skin (1). Reasons for Recurrence Score failure included insufficient RNA (17), poor quality RNA (1), failed QC (4), and other (3). The mean Recurrence Score from the 23 metastatic sites was 35 (range: 1–66). Notably, 70% (16/23) of successful metastatic biopsies yielded Recurrence Scores in the high-risk range (>25). None of the 23 metastatic biopsies gained HER2 by RT-PCR. Among the 18 paired samples, higher recurrence score results were observed in all but three of the metastatic biopsy samples with mean Recurrence Score results of 20 (range 7 to 41) for the primary and 35 (range 1-66) for the metastatic site. For paired samples, 72% of metastatic biopsies yielded Recurrence Scores >25 compared to 17% of primary sample. Primary Recurrence Scores were not predictive of metastatic scores (r2=0.052). Estrogen receptor (ER) expression status was conserved in 87% whereas progesterone receptor (PR) was lost in 69% of the metastatic lesion. Among the pairs, 5 had de novo metastatic disease. In these, the Recurrence Score was higher in the metastatic biopsy in each case compared to the matched primary (mean 36 versus 23, respectively). Among de novo cases, there was 100% concordance in ER positive and HER2 negative expression and only 60% concordance in PR expression between primary and metastatic sites. Conclusion: Using standard of care metastatic biopsy samples, a Recurrence Score result was successfully generated in 48% of samples including bone. This small series demonstrates wide variability in Recurrence Score results in metastatic disease with overall higher scores, common loss of PR, and minimal correlation to matched primary disease. Further examination of the potential significance of the Recurrence Score for treatment decisions in the metastatic setting requires additional tissue sampling during biopsy as insufficient RNA was the primary reason for failure. Citation Format: Julie Anne L Gemmill, Patricia Thompson, Rebecca Batiste, Caterina Vacchi-Suzzi, Christina Preece, Jules Cohen, Lea Baer, Carolyn Mies, Michelle Turner, Christy A Russell, Alison Stopeck. The feasibility of obtaining oncotype DX breast recurrence score® results from metastatic sites of patients with hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-37.

Percutaneous Spine Biopsy: A Review of the Current Literature.

Spine lesions are often the result of pathologic processes elsewhere in the body; prompt and accurate diagnosis are crucial to optimize treatment. Despite modern advances in imaging modalities, definitive diagnosis ultimately requires biopsy and histologic analysis. Although open surgical biopsy has traditionally been considered the benchmark, percutaneous image-guided needle biopsy of the spine has proven to be a safe and highly effective method in making a diagnosis. Choosing the optimal biopsy approach, instrumentation and modality of image guidance may depend on a number of factors including lesion type, location, and level within the spine. Knowledge of relevant anatomy, indications, contraindications, and potential complications are critical to a successful biopsy procedure.

Safety and Efficacy of Ultrasound-Guided Percutaneous Core Needle Biopsy of Pancreatic and Peripancreatic Lesions Adjacent to Critical Vessels.

PurposeTo evaluate the safety and efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of pancreatic and peripancreatic lesions adjacent to critical vessels.Materials and MethodsData were collected retrospectively from 162 patients who underwent USPCB of the pancreas (n = 98), the peripancreatic area adjacent to the portal vein, the paraaortic area adjacent to pancreatic uncinate (n = 34), and lesions on the third duodenal portion (n = 30) during a 10-year period. An automated biopsy gun with an 18-gauge needle was used for biopsies under US guidance. The USPCB results were compared with those of the final follow- up imaging performed postoperatively. The diagnostic accuracy and major complication rate of the USPCB were calculated. Multiple factors were evaluated for the prediction of successful biopsies using univariate and multivariate analyses.ResultsThe histopathologic diagnosis from USPCB was correct in 149 (92%) patients. The major complication rate was 3%. Four cases of mesenteric hematomas and one intramural hematoma of the duodenum occurred during the study period. The following factors were significantly associated with successful biopsies: a transmesenteric biopsy route rather than a transgastric or transenteric route; good visualization of targets; and evaluation of the entire US pathway. In addition, the number of biopsies required was less when the biopsy was successful.ConclusionUSPCB demonstrated high diagnostic accuracy and a low complication rate for the histopathologic diagnosis of pancreatic and peripancreatic lesions adjacent to critical vessels.

Prior PSMA PET-CT Imaging and Hounsfield Unit Impact on Tumor Yield and Success of Molecular Analyses from Bone Biopsies in Metastatic Prostate Cancer.

Simple SummaryProstate cancer is currently the fifth leading cause of death in men worldwide. To personalize and guide treatment in prostate cancer, identification of druggable genomic alterations is of major importance. Prostate cancer often metastasizes solely or predominantly to the bones, with molecular analyses on bone biopsies challenging due to technical difficulties to identify and obtain biopsies from high tumor cell containing locations. In our retrospective analysis, we showed a significantly higher success rate in patients where biopsy location was selected by a prior PSMA PET-CT compared to solely CT or MRI. CT-guided biopsies in locations with low Hounsfield units (HUs) and deviation of HUs were associated with a higher proportion of successful histological and molecular biopsies. Based on these results, we designed a simple prediction model for daily clinical practice to increase the success rate of bone biopsies for molecular analyses in prostate cancer to guide precision medicine.Developing and optimizing targeted therapies in metastatic castration-resistant prostate cancer (mCRPC) necessitates molecular characterization. Obtaining sufficient tumor material for molecular characterization has been challenging. We aimed to identify clinical and imaging variables of imaging-guided bone biopsies in metastatic prostate cancer patients that associate with tumor yield and success in obtaining molecular results, and to design a predictive model: Clinical and imaging data were collected retrospectively from patients with prostate cancer who underwent a bone biopsy for histological and molecular characterization. Clinical characteristics, imaging modalities and imaging variables, were associated with successful biopsy results. In our study, we included a total of 110 bone biopsies. Histological conformation was possible in 84 of all biopsies, of which, in 73 of the 84, successful molecular characterization was performed. Prior use of PSMA PET-CT resulted in higher success rates in histological and molecular successful biopsies compared to CT or MRI. Evaluation of spine biopsies showed more often successful results compared to other locations for both histological and molecular biopsies (p = 0.027 and p = 0.012, respectively). Low Hounsfield units (HUs) and deviation (Dev), taken at CT-guidance, were associated with histological successful biopsies (p = 0.025 and p = 0.023, respectively) and with molecular successful biopsies (p = 0.010 and p = 0.006, respectively). A prediction tool combining low HUs and low Dev resulted in significantly more successful biopsies, histological and molecular (p = 0.023 and p = 0.007, respectively). Based on these results, we concluded that site selection for metastatic tissue biopsies with prior PSMA PET-CT imaging improves the chance of a successful biopsy. Further optimization can be achieved at CT-guidance, by selection of low HU and low Dev lesions. A prediction tool is provided to increase the success rate of bone biopsies in mCRPC patients, which can easily be implemented in daily practice.

Use of fluorescein sodium to obtain histological diagnosis of primary Central nervous system lymphoma ghost tumour despite disappearance on intraoperative magnetic resonance imaging: technical note and review of the literature

Background and importance Corticosteroid pre-treatment in patients with primary central nervous system lymphoma (PCNSL) can lead to the phenomenon of ghost tumours (GhT). This affects the diagnostic yield of biopsies and potentially causes misdiagnosis of the condition. The usual strategy of neuronavigation using preoperative magnetic resonance imaging (MRI) or localisation using intraoperative MRI (iMRI) can be rendered ineffective in this situation. Clinical presentation A middle-aged Chinese male with newly diagnosed human immunodeficiency virus infection was found to have an intracranial lesion suggestive of PCNSL. Preoperatively corticosteroid led to an attenuation of the contrast enhancing lesion on iMRI. However, intraoperative use of FS allowed the successful identification, biopsy and diagnosis of the condition. Conclusion FS is useful in the biopsy of PCNSL GhT even when the lesion is not seen in subsequent MRI imaging.

Response to the letter to the editor

We thank the authors of the letter to the editor regarding our article “Digital Breast Tomosynthesis (DBT)-Guided Biopsy of Calcifications: Pearls and Pitfalls.” We appreciate their comments and their further inquiry about DBT-guided biopsies. We would like to reiterate that our article serves as an overview of DBT-guided biopsies of calcifications using only our experience with our own biopsy devices as stated in the paper. There are several devices available in the market, and there are various methods for performing successful biopsies under DBT guidance which may differ from our approach.

This Month in Adult Urology

This Month in Adult Urology

EPID-27. THE VANISHING TUMOR PHENOMENON IN THE DIAGNOSIS OF PRIMARY CNS LYMPHOMA

Abstract INTRODUCTION Steroid is commonly initiated for newly recognized brain tumors. For primary CNS lymphoma (PCNSL), however, its lympholytic effect can partially treat the tumor and obfuscate the surgical-pathological diagnosis needed to initiate chemotherapy. Evidence for this remains controversial. In this study we investigated the incidence of the vanishing tumor phenomenon and its association with steroid use. METHODS Patients > age 18 with PCNSL were identified from January 1, 2000 to April 30, 2020 within the University of Michigan Health System. Clinic and operative notes, pathology, imaging, and lumbar puncture results were reviewed. Inclusion required histopathologic diagnosis from brain tissue, cerebrospinal fluid, or autopsy, including diagnosis on repeat biopsy. Patients with prior/concurrent systemic lymphoma, HIV, organ transplant, or diagnosis established from primary ocular disease were excluded. Date(s) of biopsy, steroid initiation, and recurrence (by imaging) were abstracted. We defined vanishing tumor as a lesion whose radiographic improvement or disappearance resulted in deferred or nondiagnostic biopsy, with later confirmation of PCNSL. Steroid use and vanishing tumor were modeled using univariable logistic regression. RESULTS We identified 162 cases of PCNSL, of which 103 patients (63.6%) received steroids prior to biopsy. Twenty-three had vanishing tumor: 11 with deferred biopsies, 12 with non-diagnostic biopsies. Twenty-two of the 23 received steroid. Mean cumulative dose, in dexamethasone equivalents, was 555 + 704 mg prior to nondiagnostic/deferred biopsy (N=17) compared to 186 + 376 mg prior to successful biopsy (N=76) (Wilcoxon p< .001). Median time to recurrence after deferred or non-diagnostic biopsy (N=21) was 53 days (range: 8–648); two cases never recurred. Steroid use increased the risk of vanishing tumor by 14% per 100 mg dexamethasone equivalent (95% CI of odds ratio [1.03–1.29], p=0.02). CONCLUSION Vanishing tumor phenomenon is common in PCNSL, delays diagnosis, and is driven by steroid use.

Cholangioscopy- versus fluoroscopy-guided transpapillary mapping biopsy for preoperative evaluation of extrahepatic cholangiocarcinoma: a prospective randomized crossover study.

To evaluate the lateral extent of extrahepatic cholangiocarcinoma, the value of cholangioscopy-guided mapping biopsy (CMB) compared with that of fluoroscopy-guided mapping biopsy (FMB) remains unknown. The aim of this study was to compare these two techniques. In this prospective, randomized, crossover study, both CMB and FMB techniques were performed for all patients in a randomized order. Target sites for the mapping biopsy were determined based on resection lines of possible surgical procedures. At least two biopsy strokes were attempted at each target site. The primary outcome was the rate of site-based successful biopsies, which was defined as acquisition of epithelium-containing material appropriate for diagnosing benignancy/malignancy from each site, regardless of amount of materials obtained from the same site. Between September 2016 and October 2018, 28 patients (16 distal bile duct cancer and 12 perihilar bile duct cancer) were enrolled and divided into two groups of 14 patients: CMB first and FMB first. Although all 118 target sites could be approached using CMB, FMB forceps reached only 71% of them with significantly poor accessibility to the B2/3 confluence. Since several materials were too small and did not contain epithelium, the overall rates of site-based successful biopsies were 78% (92/118) using CMB and 64% (76/118) using FMB (P = 0.031). The rate of site-based successful biopsies using CMB was significantly higher than that using FMB when evaluated using specimens obtained from several biopsy strokes.

Severe Conjunctival Papilloma in a Six year old female - Case report

Conjunctival papilloma is a benign growth arising from the stratified squamous epithelium of the conjunctiva. It is mostly a self-limiting growth. Conjunctival papilloma occurs commonly in male adults especially in their third and fourth decades of life. It rarely occurs in children. This is a case report of a six (6) year-old female patient who was seen at the Solwezi General Hospital Eye Clinic (SGHEC) with complaints of difficulties in seeing, sandy sensation and tearing of the right eye. The patient had a twelve-month history of multiple fleshy growths on the conjunctival surface of the right eye, referred from a rural health centre in the District. A clinical diagnosis of conjunctival papilloma was made at SGHEC and the child was referred to Kitwe Teaching Eye Hospitals (KTEH) for furthermanagement. At Kitwe Teaching Eye Hospital, a successful excisional biopsy of the conjunctival papilloma lesions on the right eye was conducted with adjunctive therapy of Mitomycin-C intraoperatively, and topical chemotherapy of 5- fluorouracil (5-FU) after surgery. A definitive diagnosis of Benign Conjunctival Papilloma was confirmed for the patient's condition, based on the results from the histopathology samples that were sent to the Cancer Disease Hospital in Lusaka.

CT-guided blood tattoo for thoracoscopic excision of lung lesions in pediatric patients

BackgroundTo describe a single-institutional experience with an innovative technique using CT-guided injection of autologous blood for localization of nonpleural-based pulmonary nodules prior to thoracoscopic excisional biopsy in pediatric patients.MethodsA retrospective review of all patients under the age of 18 with lung lesions suspected to be malignant that were not pleural-based lesions and were not of adequate size to visualize at thoracoscopy, who underwent CT-guided blood tattoo (CGBT) localization between 2006–2019. CGBT was performed under general anesthesia by injecting 0.5–10 mL of autologous blood into the area of the lesions. The patients were then immediately transferred from interventional radiology to the operating room for thoracoscopic excision of the lesion. Demographics, location of lesions, indication for biopsy, and pathology were reviewed.ResultsIn eleven pediatric patients (ages ranging from 4–18 years), preoperative CGBT localization of pulmonary nodules resulted in successful thoracoscopic excisional biopsy. All resections were diagnostic and 82% (9/11 cases) represented a metastatic malignancy as confirmed by pathology. Malignant nodules ranged from 2 to 14 mm in size, while a 13 mm nodule in a patient with history of AML was determined to be an organizing pneumonia and a 12 mm nodule in a second patient revealed a caseating granuloma consistent with Crohn’s disease. One patient with a failed attempt at excisional biopsy without preoperative localization then underwent CGBT one week later with successful thoracoscopic excision of the nodule.ConclusionsCT-guided blood tattoo is a safe option for localization of nonpleural-based lung nodules prior to thoracoscopic excision in pediatric patients.

Comparison of pain levels in fusion prostate biopsy and standard TRUS-Guided biopsy.

ABSTRACTObjectives Fusion prostate biopsy (FPB) has recently emerged as a popular and successful biopsy technique on diagnosis of prostate cancer. The aim of this study was to compare the pain levels in TRUS-guided standard 12-core prostate biopsy (SPB) and MpMRI-guided FPB.Materials and Methods Patients detected with a PI-RADS (Prostate Imaging Reporting and Data System) ≥3 lesion on MpMRI underwent MpMRI-guided FPB (Group I) and the patients who had no suspected lesions or had a PI-RADS <3 lesion on MpMRI underwent TRUS-guided SPB (Group II). Pain assessment was performed using Visual Analog Scale (VAS) five minutes after the procedure. Following the procedure, the patients were asked to indicate the most painful biopsy step among the three steps.Results 252 patients were included in this study (Group I=159, Group II=93). The mean number of cores and the malignancy detection rate were significantly higher in Group I compared to Group II (p <0.001, p=0.043, respectively). No significant difference was found between the two groups with regard to VAS scores (p=0.070). The most painful part of the whole procedure was revealed to be the insertion of the probe into the rectum. However, no significant difference was found between the two groups with regard to the most painful biopsy step (p=0.140).Conclusion FPB, with a relatively higher cancer detection rate, leads to the same pain level as SPB although it increases the number of biopsy cores and involves a more complex procedure compared to SPB. Further prospective studies with larger patient series are needed to substantiate our findings.

A prospective multicenter international single-arm observational study on the oncological safety of the sentinel lymph node algorithm in stage I intermediate-risk endometrial cancer (SELECT, SEntinel Lymph node Endometrial Cancer Trial)

BackgroundIn the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node...

An effective method for trophectoderm biopsy using mechanical blunt dissection: a step-by-step demonstration

To present an effective approach to trophectoderm biopsy for blastocysts of different stages and characteristics by mechanical blunt dissection (MBD). Stepwise demonstration with still pictures and operational video clips to explain tips and tricks for trophectoderm biopsy. (This demonstration was approved by the Reproductive Study Ethics Committee at Shengjing Hospital of China Medical University.) SETTING: Invitro fertilization laboratory. Patients who underwent preimplantation genetic testing. The illustrated techniques of blastocyst trophectoderm biopsy using micromanipulation methods include artificial shrinkage, zona pellucida drilling, injecting media from the drilling, aspiration of trophectoderm cells into the biopsy pipette (outer diameter 27 μm for fully expanded blastocysts and peanut-shaped hatching blastocysts; outer diameter 20 μm for 8-shaped hatching and hatched blastocysts), detachment of the trophectoderm cells by laser pulse combined with MBD (performed using the rims of the biopsy and holding pipettes), and release of the biopsy fragment. Successful biopsy rate and survival after warming. Our biopsy strategy does not involve assisted hatching on day-3 or day-4 embryos, which can leave the embryo undisturbed in culture up to the expanded blastocyst stage. Notably, this approach demonstrates several noteworthy advantages for sampling blastocysts of different stages and characteristics, and it maintains a desirable successful biopsy rate (95.4%, n = 1,872) and survival rate after warming (100%, n = 440). The MBD method may reduce thermal damage because fewer laser pulses are used, compared with the traditional laser-only biopsy techniques. For noncollapsed blastocysts after artificial shrinkage, the strategy of injecting medium from the zona pellucida drilling helps to separate the trophectoderm cells from the zona pellucida, thus facilitating the biopsy procedure. For peanut-shaped hatching blastocysts, this approach could provide better control over the aspiration of trophectoderm cells into the biopsy pipette. Especially if the inner cell mass is herniating from the zona pellucida, the trophectoderm biopsy can be performed away from the inner cell mass to avoid damaging it. In addition, the MBD approach combined with the biopsy pipette (outer diameter 20 μm) can effectively control the target number of trophectoderm cells, thus simplifying the process of obtaining a biopsy from a hatched blastocyst. Our biopsy approach demonstrates several noteworthy advantages. Considering its benefits and the simplicity of its execution, this systematic biopsy method for blastocysts of different stages and characteristic can be widely applied.

MRI-targeted prostate biopsy: key considerations for pathologists.

We discuss the role of the pathologist for MRI-targeted prostate biopsy with a focus on specimen processing, reporting of pathological findings and quality assurance in establishing a successful MRI-targeted biopsy programme. The authors discuss the current issues relevant to pathologists regarding MRI-targeted prostate biopsy. In addition, a brief review of the recently published literature was performed using an English literature search on PubMed with a focus on original investigations related to MRI-targeted prostate biopsy. Our search terms included the following: 'prostate cancer', 'pathology', 'histology', 'reporting', 'cores', 'imaging', 'MRI' and 'mpMRI'. Prostate multiparametric magnetic resonance imaging (mp-MRI) and MRI-targeted biopsy has been shown to improve the diagnosis of clinically significant prostatic adenocarcinoma and can affect the management of patients with prostate cancer. The current active surveillance guidelines were based on data from TRUS biopsies and not MRI-targeted biopsies. MRI-targeted biopsy acquires multiple cores of tissue from one or more suspicious lesions found on mp-MRI. The way in which multiple targeted core biopsies obtained from a single image-directed region of interest are analysed and reported can potentially alter the Gleason score and tumour burden as reported on biopsy, which could undoubtedly alter patient management. Pathologists play an important role in the reporting of MRI-targeted prostate biopsies. How we report prostate cancer grade and extent on these biopsies can influence patient management. In addition, the pathologist should be involved in the quality assurance for patients undergoing MRI-targeted prostate biopsy.

Tips to start an MR-US fusion biopsy program.

There is growing evidence that MRI-ultrasound (MR-US)-targeted biopsy (TB) has high detection rates of clinically significant prostate cancer (PCa) compared to standard transrectal ultrasound (TRUS)-guided biopsy. A radiologist plays a significant role in MR-US fusion biopsy planning. Here, we discuss six simple steps that can help set up a successful MR-US fusion biopsy program in collaboration with the urologist.

Plasma-Derived Extracellular Vesicle Phosphoproteomics through Chemical Affinity Purification.

The invasive nature and the pain caused to patients inhibit the routine use of tissue biopsy-based procedures for cancer diagnosis and surveillance. The analysis of extracellular vesicles (EVs) from biofluids has recently gained significant traction in the liquid biopsy field. EVs offer an essential "snapshot" of their precursor cells in real time and contain an information-rich collection of nucleic acids, proteins, lipids, and so on. The analysis of protein phosphorylation, as a direct marker of cellular signaling and disease progression could be an important stepping stone to successful liquid biopsy applications. Here we introduce a rapid EV isolation method based on chemical affinity called EVtrap (extracellular vesicle total recovery and purification) for the EV phosphoproteomics analysis of human plasma. By incorporating EVtrap with high-performance mass spectrometry (MS), we were able to identify over 16 000 unique peptides representing 2238 unique EV proteins from just 5 μL of plasma sample, including most known EV markers, with substantially higher recovery levels compared with ultracentrifugation. Most importantly, more than 5500 unique phosphopeptides representing almost 1600 phosphoproteins in EVs were identified using only 1 mL of plasma. Finally, we carried out a quantitative EV phosphoproteomics analysis of plasma samples from patients diagnosed with chronic kidney disease or kidney cancer, identifying dozens of phosphoproteins capable of distinguishing disease states from healthy controls. The study demonstrates the potential feasibility of our robust analytical pipeline for cancer signaling monitoring by tracking plasma EV phosphorylation.

Cauda equina biopsy as a tool in the diagnosis of malignant tumors

The prevalence of malignant lymphoma is increasing. With the advent of novel therapeutic approaches, the distinct pathology of each type of malignant lymphoma is used to tailor its treatment for the most effective outcome. Therefore, analysis of the malignant cell pathophysiology within the cauda equina is important to devising a treatment strategy. In some cases, the tumor only invades the cauda equina. Composed of an uninterrupted bundle of nerve fibers, the cauda equina is more complex than the brain parenchyma; hence, the method for performing a biopsy of the cauda equina is relatively more challenging and requires improvement. The appropriate surgical procedure to confirm the posterior ramus, which consists of sensory roots, is mandatory. In the lumbar region, the denticulate ligaments that distinguish between the motor and sensory nerve roots do not exist. Microsurgical techniques and neurophysiological monitoring can aid with removal of posterior roots and allow for the reliable performance of a cauda equina biopsy. First, we determined where the spinal root pierces the dura mater, and then we performed electromyography. We performed cauda equina biopsy with this method for patients with malignant lymphoma and reviewed the efficacy of this procedure. This strategy prevented postoperative neurological impairments and provided detailed information to ensure optimal adjuvant therapy. Based on advances in personalized therapies for malignant tumors, opportunities for cauda equina biopsy are increasing. Our method using both morphological feature observation and neurophysiological monitoring may contribute to successful biopsy of the cauda equina.

Intraindividual comparison between 68Ga-PSMA-PET/CT and mpMRI for intraprostatic tumor delineation in patients with primary prostate cancer: a retrospective analysis in 101 patients

PurposeAccurate delineation of intraprostatic gross tumor volume (GTV) is mandatory for successful fusion biopsy guidance and focal therapy planning of prostate cancer (PCa). Multiparametric magnetic resonance imaging (mpMRI) is the current gold standard for GTV delineation; however, prostate-specific membrane antigen positron emission tomography (PSMA-PET) is emerging as a promising alternative. This study compares GTV delineation between mpMRI and 68Ga-PSMA-PET in a large number of patients using validated contouring approaches.MethodsOne hundred one patients with biopsy-proven primary PCa who underwent mpMRI and 68Ga-PSMA-PET within 3 months before primary treatment were retrospectively enrolled. Clinical parameters (age, PSA, Gleason score in biopsy) were documented. GTV based on MRI and PET images were delineated; volumes measured and laterality determined. Additionally, biopsy data from 77 patients was analyzed. Univariate and multivariate binary logistic regression analyses were performed using concordance in laterality as the endpoint.ResultsIn total mpMRI and 68Ga-PSMA-PET detected 151 and 159 lesions, respectively. Median GTV-MRI (2.8 ml, 95% CI 2.31–3.38 ml) was significantly (p < 0.0001) smaller than median GTV-PET (4.9 ml, 95% CI 3.9–6.6 ml). 68Ga-PSMA-PET detected significantly more bilateral lesions than mpMRI (71 vs 57, p = 0.03). Analysis of patients with bilateral lesions in biopsy showed a significant higher concordance of laterality in 68Ga-PSMA-PET (p = 0.03). In univariate analysis, PSA level and volume of GTV-MRI had an impact on concordance in laterality (p = 0.02 and p = 0.01), whereas in multivariate analysis, only GTV-MRI volume remained significant (p = 0.04).ConclusionMpMRI and 68Ga-PSMA-PET detect a similar amount of PCa lesions. However, GTV-PET had approximately twice the volume (median 4.9 ml vs 2.8 ml) and detected significantly more bilateral lesions than mpMRI. Thus, 68Ga-PSMA-PET gives highly important complementary information. Since we could not find any strong evidence for parameters to guide when 68Ga-PSMA-PET is dispensable, it should be performed additionally to MRI in patients with intermediate and high-risk PCa according to D’Amico classification to improve GTV delineation.