Invasive Biopsy Methods Research Articles

From photonic technologies to microfluidics-A review on the techniques which revolutionize liquid biopsy, opening a new era in cancer therapy.

Cancer therapy is one of the most researched upon medical field in the world. Non invasive technologies such as liquid biopsy are gaining more importance in cancer therapy because of their manifold advantages over traditional invasive biopsy methods. Liquid biopsy is used to analyze nucleic acids such as ctDNA, cfDNA and RNA, cellular and subcellular components such as proteins, extracellular vesicles and circulating tumor cells in various biological fluids such as blood, urine, cerebrospinal fluid, pleural fluid and ascites fluid for diagnosis of cancer. Liquid biopsy has a wide range of applications such as assessment of residual diseases and tumors which cannot be biopsied easily and prediction of CAR-T response and response to immune checkpoint inhibitors. It can also be used to know the efficacy of cancer drugs in a patient by analyzing multiple samples. Liquid biopsy is becoming more popular as it allows biopsy of those samples in which solid tumor biopsies are challenging or impracticable. To achieve comprehensive insight on the status of cancer in a patient, various cutting edge liquid biopsy techniques have been developed. Microfluidics and photonic technologies, along with PCR, next generation sequencing, advanced and innovative molecular and cell biology approaches and imaging techniques have expanded the domain of liquid biopsy and elevated the accuracy of liquid biopsy results. This review discusses about the contributions of some widely used methods along with microfluidics and photonic technologies in detection of cancer biomarkers by liquid biopsy.

Characterizing the accuracy of robotic bronchoscopy in localization & targeting of small pulmonary lesions.

Considering the recent implementation of lung cancer screening guidelines, it is crucial that small pulmonary nodules are accurately diagnosed. There is a significant need for quick, precise, and minimally invasive biopsy methods, especially for patients with small lung lesions in the outer periphery. Robotic bronchoscopy (RB) has recently emerged as a novel solution. The purpose of this study was to evaluate the accuracy of RB compared to the existing standard, electromagnetic navigational bronchoscopy (EM-NB). A prospective, single-blinded, and randomized-controlled study was performed to compare the accuracy of RB to EM-NB in localizing and targeting pulmonary lesions in a porcine lung model. Four operators were tasked with navigating to four pulmonary targets in the outer periphery of a porcine lung, to which they were blinded, using both the RB and EM-NB systems. The dependent variable was accuracy. Accuracy was measured as a rate of success in lesion localization and targeting, the distance from the center of the pulmonary target, and by anatomic location. The independent variable was the navigation system, RB was compared to EM-NB using 1:1 randomization. Of 75 attempts, 72 were successful in lesion localization and 60 were successful in lesion targeting. The success rate for lesion localization was 100% with RB and 91% with EM- NB. The success rate for lesion targeting was 93% with RB and 80% for EM-NB. RB demonstrated superior accuracy in reaching the distance from the center of the lesion, at 0.62mm compared to EM-NB at 1.28mm (p = 0.001). Accuracy was improved using RB compared to EM- NB for lesions in the LLL (p = 0.025), LUL (p < 0.001), and RUL (p < 0.001). Our findings support RB as a more accurate method of navigating and localizing small peripheral pulmonary targets when compared to standard EM-NB in a porcine lung model. This may be attributed to the ability of RB to reduce substantial tissue displacement seen with standard EM-NB navigation. As the development and application of RB advances, so will the ability to accurately diagnose small peripheral lung cancer nodules, providing patients with early-stage lung cancer the best possible outcomes.

Endovascular biopsy in neurointerventional surgery: A systematic review.

Endothelial cells (ECs) continuously line the cerebrovasculature. Molecular aberrations in the ECs are hallmarks and contributory factors to the development of cerebrovascular diseases, including intracranial aneurysms and arteriovenous malformations (AVMs). Endovascular biopsy has been introduced as a method to harvest ECs and obtain relevant biologic information. We aimed to summarize the literature on endovascular biopsy in neurointerventional surgery. We conducted a comprehensive literature search in multiple databases, identifying eligible studies focusing on neurosurgical applications of endovascular biopsy. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The relevant information was collected, including study characteristics, biopsy techniques, and key findings. Nine studies met the inclusion criteria and were included. The studies involved the collection of ECs using various endovascular devices including coils, guide wires, different stents, and forceps. Endothelial-enrichment techniques, such fluorescence-activated cell sorting (FACS), collected ECs and facilitated downstream applications of bulk or single-cell RNA sequencing (scRNAseq). The studies provided insights into gene expression profiles and identified potential biomarkers associated with intracranial aneurysms. However, challenges were observed in obtaining an adequate number of ECs and identifying consistent biomarkers. Endovascular biopsy of endothelial cells (ECs) in cerebrovascular pathologies shows promise for gene expression profiling. However, many studies have been limited in sample size and underpowered to identify "signature genes" for aneurysm growth or rupture. Advancements in minimally invasive biopsy methods have potential to facilitate applications of precision medicine in the treatment of cerebrovascular disorders.

Preparation, Characterization, and Radiolabeling of Anti-HER2 scFv With Technetium Tricarbonyl and Stability Studies.

Breast cancer is the most common diagnosed cancer, and the second cause of cancer death among women, worldwide. HER2 overexpression occurred in approximately 15% to 20% of breast cancers. Invasive biopsy method has been used for detection of HER2 overexpression. HER2-targeted imaging via an appropriate radionuclide is a promising method for sensitive and accurate identification of HER2+ primary and metastatic lesions. 99mTc-anti-HER2 scFv can specifically target malignancies and be used for diagnosis of the cancer type and metastasis as well as treatment of breast cancer. We radiolabeled anti-HER2 scFv that was expressed in Escherichia coli and purified through Ni-NTA resin under native condition with 99mTc-tricarbonyl formed from boranocarbonate. HER2-based ELISA, BCA, TLC, and HPLC were used in this study. In the current study, anti-HER2 scFv was lyophilized before radiolabeling. It was found that freeze-drying did not change the binding activity of anti-HER2 scFv to HER2. Results demonstrated direct anti-HER2 scFv radiolabeling by 99mTc-tricarbonyl to hexahistidine sequence (His-tag) without any changes in biological activity and radiochemical purity of around 98%. Stability analysis revealed that 99mTc-anti-HER2 scFv is stable for at least 24 h in PBS buffer, normal saline, human plasma proteins, and histidine solution.

It’s All in the Details

Cancer is estimated to affects around half of Canadian population in their lifetime. Often a fatal disease, it costs billions to Canadian healthcare system yearly. Cancer diagnosis, and subsequent prognosis and treatment, all require characterization of tumor cell morphology and genotype, which is conventionally done using invasive biopsy methods. However, less invasive modalities exist and include liquid biopsy – sampling of body fluids for cancer cells and cellular material. It is less invasive compared to majority of conventional practices and yields a variety of biomarkers for further laboratory analysis. Analytical techniques including aptamers – a synthetic analogue to antibodies with increased affinity to target, allow for robust analysis of molecular data. This article discusses directions of research and current applications of these innovations and implications to diagnosis in clinical practice.

A novel clinical decision support system for liver fibrosis using evolutionary multi-objective method based numerical association analysis

Chronic liver diseases are among the major health problems in the world. Determining the degree of fibrosis and structural changes and early diagnosis is an important indicator for the course of chronic liver disease, screening of complications and response to treatment. Considering the prevalence of the disease, the use of an invasive biopsy method does not seem practical. At least a preliminary assessment should be able to determine which patients should have a biopsy. In addition, it is not possible to repeat the liver biopsy frequently to follow the course of the patients. Liver biopsy is expensive and it cannot be performed in every hospital. Difficulties in the application for physicians and patients, sampling errors, differences in evaluation, the requirement of a trained physician, difficulties to repeat, and serious complications during the procedure are other disadvantages. The association rule discovery aims to find interesting and valuable associations within the data. Although association analysis is a very useful and popular task in data mining, as far as we know, there is not any study about association analysis of liver fibrosis. We hypothesize at this work that, evolutionary multi-objective methods can be very efficiently modeled and adapted for the automatic miner of comprehensible, accurate, and interesting numerical positive and negative association rules in liver fibrosis clinical decision making. Due to the numerical valued attributes in liver fibrosis data, for the first time, evolutionary intelligent MOPNAR was handled as a rule miner from liver fibrosis without using any discretizing process that requires domain experts. The algorithms modeled for a clinical decision support system in this study modify and adapt themselves for automatic discovery of numerical association rules and do not require modifying or changing the data. Sensitivity analysis of MOPNAR for liver fibrosis was also performed for the first time and a better parameter setting for this task was presented. According to the discovered rules in liver fibrosis data, the MOPNAR outperformed the compared method with respect to average confidence, lift, certainty factor, netconf, yulesQ, number of attributes, and number of covered records.

Fine-needle aspiration biopsy for the diagnosis of bone and soft tissue lesions: a systematic review and meta-analysis

The workup of musculoskeletal (MSK) lesions utilizes a range of diagnostic tests including incisional biopsy, core needle biopsy, and fine-needle aspiration (FNA). FNA is the most cost-effective and least invasive biopsy method, but variation in its reported diagnostic performance has constrained its use for MSK lesions. Herein, we undertake a meta-analysis to clarify the diagnostic performance of FNA for bone and soft tissue lesions. A systematic search was run in MEDLINE, EMBASE, and CINAHL. Included studies were aggregated for pooled estimates of adequacy, accuracy, and sensitivity/specificity for all MSK lesions as well as bone and soft tissue independently. Analysis of heterogeneity and risk of bias were assessed across studies. Covariate subgroup analyses were attempted to investigate potential influences on diagnostic accuracy. Twenty-five articles met inclusion criteria, representing 4604 FNAs. Adequacy was 92.3% (range: 59.2%-98.0%, S = 9.4%), and sensitivity/specificity for the nature (malignant or benign) of the lesion was 95.6% (95% CI: 94.5%-96.5%) and 96.9% (95% CI: 95.9%-97.7%). FNA was 75.8% accurate (range: 42.5%-99.3%, S = 17.3%) for definitive diagnosis. FNA provides higher accuracy for benign versus malignant nature in bone lesions but achieves a definitive diagnosis more frequently in soft tissue lesions. The results of this meta-analysis support the expanded use of FNA in the diagnostic workup of bone and soft tissue lesions, particularly in light of a sensitivity and specificity comparable to incisional and core needle biopsy.

A Safe and Minimally Invasive Method for Thoracoscopic Lung Biopsy in Interstitial Lung Disease.

Background: Interstitial lung disease (ILD) represents a spectrum of lung diseases that may contain different levels of fibrosis and inflammation. Sometimes, the clinical picture and imaging studies are insufficient to determine the diagnosis and lung biopsy becomes crucial, which may be performed in a thoracoscopic or open manner. The aim of this study was to present a new minimally invasive biopsy method that seems to be technically easy, safe, and inexpensive. Herein, we present a minimally invasive method for thoracoscopic lung biopsy using a Vicryl loop. Methods: The charts of patients with suspected ILD who underwent thoracoscopic lung biopsy using a Vicryl loop between 2007 and 2017 were analyzed retrospectively. Results: Nine patients were identified, four were boys and five were girls. The median age was 76 months. The mean weight of the patients was 10.9 kg. The mean chest tube removal time was 3.8 days. The mean surgical time was 37 minutes. There was an air leakage for 13 days in one child postoperatively. Conclusions: Thoracoscopic lung biopsy with a knot and scissors is an easily applicable and minimally invasive method that may be performed in children with suspected ILD.

Teaching and learning FNA biopsy: An update for the modern audience

Teaching and learning FNA biopsy: An update for the modern audience

Prognostic value of some inflammatory markers in patients with lymphoma.

Background: Lymphoma is a group of blood cell tumors which develop from lymphocytes. The main forms of lymphoma are Hodgkin lymphoma (HL) and non-HL (NHL). Cytokines may contribute to lymphoma and they are related to risk NHL and HL. Aim: Assessment of the serum level of certain inflammatory markers as complementary indicators to confirm diagnosis of lymphoma patients that may be subjected to more invasive biopsy methods. Method: The serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), and eotaxin were assessed by Bio-Plex Pro assays in 81 lymphoma patients and 44 NHL and 37 HL patients before and after chemotherapy treatment as well as 20 healthy persons as a control group. Results: Lymphoma patients showed significantly raised marker levels before treatment and significantly reduced levels related to pre-treatment and controls of post-treatment for most of the markers. MCP-1 reported the highest diagnostic accuracy. G-CSF significantly raised pre-treatment and TNF-α. MCP-1 significantly increased in post treated HL compared with NHL. In order to distinguish HL from NHL, G-CSF reported the highest diagnostic accuracy. NHL patients reported complete remission (CR) and those who reported stable disease (SD) and progressive disease (PD) represented 25% and 38% respectively compared with 16% and 27% of HL patients, while partial remission (PR) of HL patients were 56% compared with 36% of NHL patients. Conclusion: Most of the markers were significantly increased in pre-treatment but significantly decreased post-treatment. However, it was not considerably enough to get better prognosis of the disease. Elevated serum levels of inflammatory markers correlate with disease severity and low benefit from treatment.

Electromagnetic navigation transthoracic needle aspiration for the diagnosis of pulmonary nodules: a safety and feasibility pilot study.

Pulmonary nodules remain a diagnostic challenge for physicians. Minimally invasive biopsy methods include bronchoscopy and CT guided transthoracic needle aspiration (TTNA). A novel electromagnetic guidance transthoracic needle aspiration (ETTNA) procedure which can be combined with navigational bronchoscopy (NB) and endobronchial ultrasound (EBUS) in a single setting has become available. A prospective pilot study examining the safety, feasibility and diagnostic yield of ETTNA in a single procedural setting. All patients enrolled underwent EBUS for lung cancer staging followed by NB and ETTNA. Feasibility of performing ETTNA and a safety assessment by recording procedural related complications including pneumothorax or bleeding was performed. Diagnostic yield of ETTNA defined by a definitive pathologic tissue diagnosis was recorded. An additional diagnostic yield analysis was performed using a cohort analysis of combined interventions (EBUS + NB + ETTNA). All non-diagnostic biopsies were either followed with radiographic imaging or a surgical biopsy was performed. Twenty-four subjects were enrolled. ETTNA was feasible in 96% of cases. No bleeding events occurred. There were five pneumothoraces (21%) of which only two (8%) subjects required drainage. The diagnostic yield for ETTNA alone was 83% and increased to 87% (P=0.0016) when ETTNA was combined with NB. When ETTNA and NB were performed with EBUS for complete staging, the diagnostic yield increased further to 92% (P=0.0001). This is the first human pilot study demonstrating an acceptable safety and feasibility profile with a novel ETTNA system. Further studies are needed to investigate the increased diagnostic yield from this pilot study.

Evaluation of minimally invasive muscle biopsy method for genetic analysis in horse

Abstract In horses, muscle biopsy is widely used in veterinary practice for routine diagnosis of various muscle disorders. Development of genetic methods such as gene expression measurements using microarrays, RNA-seq, and real-time PCR leads to searching an alternative, less invasive biopsy method in order to obtain an appropriately representative group of animals for genetic testing. In the present study, we proposed a minimally invasive method of muscle sample biopsy using Pro- MagTM Ultra Automatic Biopsy Instrument (Surgical Specialties Corporation, US, Inc.), which is commonly utilized in human medicine. This approach does not require skin incisions and usage of stitches. The quantity of muscle sample gained in accordance with presented procedure was sufficient to obtain RNA with a good quality. Furthermore, application of the automatic biopsy instrument allows obtaining a sufficient amount of biological material for genetic analysis from a wide variety of tissues. Moreover, samples acquired according to this method could be used in other analyses.

Extracellular microRNAs as Biomarkers in Human Disease.

Dysregulation of microRNA (miRNA) levels is observed in diverse disease states. Early studies showed that by analyzing the expression profile of miRNAs in the tissue sample of a diseased person, it was possible to classify the disease into a specific subtype. To be used for diagnostic purposes more practically, however, a less invasive method than tissue biopsy is required. Surprisingly, it was discovered that a notable amount of extracellular miRNAs circulate throughout the body fluids with high stability. Moreover, the expression profile of miRNAs was shown to differ considerably between healthy and diseased people. In addition, evidence has been accumulating of extracellular miRNAs acting as signaling molecules between distantly located cells. If the expression profile faithfully reflects the disease states, the profiling of extracellular miRNAs will become a useful means of early warning or diagnosis of diverse diseases, replacing more invasive biopsy methods.

Breast biopsy for mammographically detected non-palpable lesions using a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit.

It is planned to start screening mammography throughout Japan in the near future. However, a minimally invasive biopsy procedure for mammographically detected non-palpable breast lesions is not available in almost all Japanese hospitals. It is crucial to develop a useful minimally invasive biopsy method which can be applied without difficulty. Eighty-nine biopsies for 88 mammographically detected non-palpable breast lesions, consisting of 70 lesions with microcalcifications alone, eight masses without calcifications and 10 with both masses and microcalcifications, were performed using the combination of a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit. Microcalcifications were confirmed radiographically in the tissue obtained from 78 biopsies among 81 biopsies for the lesions with microcalcifications (96.3%). All the lesions without calcifications were considered to be biopsied successfully. Five patients complained of nausea or fainted during the localization or biopsy procedure and an additional patient suffered from hyperventilation syndrome. Five cases experienced mild subcutaneous bleeding in the breasts. The biopsy technique using the combination of a vacuum-assisted biopsy device and an upright-type stereotactic mammography unit is a cost-effective, safe and very useful method for mammographically detected non-palpable breast lesions. It is expected to be a standard method of biopsy for such lesions in many developed countries other than the USA. However, it is important to make the patients relaxed during the biopsy to prevent mental strain.

Breast biopsy for benign disease

Summary Each biopsy method has its advantages and disadvantages. For a patient whose clinical presentation, clinical history, physical examination, and mammogram indicate a low risk of malignancy, less invasive biopsy methods should be used. For a high-risk patient. the area of suspicion should be treated as malignant. The Breast Imaging Reporting and Data System is a quality assurance tool devised to standardize mammographic reporting and ascribe the need for biopsy based on mammographic criteria. These standards can be used in conjunction with clinical evidence to develop an algorithm for treatment. Each biopsy technique should be performed with regard tosubsequent therapy that will be required if the lesion is confirmed to be cancer.

Percutaneous transpedicular biopsy of thoracic and lumbar vertebrae—method and diagnostic validity

BACKGROUND Percutaneous transpedicular needle biopsy was performed on thoracic and lumbar vertebral bodies with a thin trocar (2.0 mm outer diameter) under observation with a conventional X-ray image intensifier in order to establish a correct histopathological diagnosis. We also evaluated the clinical validity of this less invasive diagnostic method in terms of the accuracy of the pathological diagnosis. METHODS Twenty-eight thoracic or lumbar vertebrae of 26 patients with abnormalities observed on routine X-ray, CT, or MRI images underwent percutaneous transpedicular needle biopsy under local anesthesia. A threaded trocar with an outer diameter of 2.0 mm was screwed into the intra-vertebral lesion through the pedicle from the posterior side under control of X-P imaging, and a small amount of tissue or fluid was collected. RESULTS For all patients but two, where inadequate specimens were obtained, correct diagnoses were made, which were confirmed by pathological diagnoses of massive tissue obtained during subsequent reconstructive surgery. CONCLUSIONS The accuracy rate of diagnosis with this biopsy method was 92% without significant intra- or postoperative complications. Therefore, it can be concluded that this less invasive biopsy method used in conjunction with conventional X-ray apparatus has good potential to result in correct preoperative diagnosis of thoracic and lumbar lesions so that more effective treatment can be determined.

Ultrasound guided forceps biopsy of the pleura

Between cytology of pleural effusion and thorascopy there is a gap for another non invasive biopsy method to diagnose pleural diseases, especially since Adam's and Ramel's blind pleural biopsy is uncommon. Therefore it is suggestive to test feasibility and usefulness of pleural forceps biopsy. It is possible to take biopsies under ultrasound guidance with the help of a biopsy-forceps from the diaphragmatic pleura or pleural appositions through a 2.5 mm canula with a stop cock and a rubber vent. The specimen can be used for histological or immunohistochemical examinations. The procedure is coducted in a closed system to avoid pneumothorax. The puncture was done in 12 patients with a puncturable pleural effusion. In 11 of 12 patients it was possible to get the final diagnosis. In one of three cases of mesotheliomas a rebiopsy was necessary. In 9 cases a malign tumor was diagnosed, effusion cytology was negative in 4 of 7 tumors. In 5 patients with a history of a former tumor pleural carcinosis was related three times correctly to the former cancer and twice to a secondary cancer. In one case a fibrous plaque was found. There were two patients with pleuritis, in one case a pulmonary tuberculosis was found 8 weeks later. In one patient with a mesothelioma inoculated metastasis were present in the sites of the punctures. In all pleural forceps punctures we got enough biopsy material for histological and immunohistochemical diagnosis. The ultrasound guided forceps biopsy of the pleura is a very promising less invasive method to diagnose pleural tumors. Additional improvements of the equipment are possible. Definitive evaluation of the procedure especially in infectious pleural diseases requires a higher number of cases.

Interphase fluorescence in situ hybridization detection of t(2;13)(q35;q14) in alveolar rhabdomyosarcoma--a diagnostic tool in minimally invasive biopsies.

The identification of t(2;13)(q35;q14) is a useful aid in the accurate diagnosis of rhabdomyosarcoma, distinguishing it from other small round cell tumours and supporting the distinction between alveolar and embryonal forms. Cytogenetic analysis is difficult and with the increased use of minimally invasive biopsy methods and primary chemotherapy, adequate tumour material is not always available. To overcome these difficulties, two-colour interphase fluorescence in situ hybridization (FISH) to detect t(2;13)(q35;q14) was developed and its utility in assessing minimally invasive biopsies was investigated. Two cosmid clones which mapped proximal or distal to the breakpoint region 13q14 and one yeast artificial chromosome clone that mapped distal to the 2q35 breakpoint were identified. In interphase cells containing t(2;13)(q35;q14), the configuration of cosmid and yeast artificial chromosome signals demonstrated the presence of the translocation. Five cases of rhabdomyosarcoma were analysed by interphase FISH. The t(2;13)(q35;q14) was detected in all four alveolar tumours and was confirmed by cytogenetics in two cases, but was absent in one embryonal tumour. This sensitive detection method is applicable to minimal amounts of fresh or frozen tumour.