Organ Biopsy Research Articles

Automatic intraluminal scanning with a steerable endoscopic optical coherence tomography catheter for gastroenterology applications

SignificanceEndoscopic optical coherence tomography (OCT) enables real-time optical biopsy of human organs. Endoscopic probes require miniaturization of optics, which in turn limits field of view. When larger imaging areas are needed such as in the gastrointestinal tract, the operator must manually scan the probe over the tissue to extend the field of view, often resulting in an imperfect scanning pattern and increased risk of missing lesions. Automatic scanning has the potential to extend the field of view of OCT, allowing the user to focus on image interpretation during real-time observations.AimThis work proposes an automatic scanning using a steerable OCT catheter integrated with a robotized interventional flexible endoscope. The aim is to extend the field of view of a low-profile OCT probe while improving scanning accuracy and maintaining a stable endoscope’s position during minimally invasive treatment of colorectal lesions.ApproachA geometrical model of the steerable OCT catheter was developed for estimating the volume of the accessible workspace. Experimental validation was done using electromagnetic tracking of the catheter’s positions. An exemplary scanning path was then selected within the available workspace to evaluate motion performance with the robotized steerable OCT catheter. Automatic scanning is compared to a teleoperated one and a manual scanning with a nonrobotized flexible endoscope. Spectral arc length, scanning area, spacing between scan trajectories, and time are metrics used to quantify performance.ResultsThe available scanning workspace was experimentally estimated to be 255 cm3. The automatic scanning mode provided the highest accuracy and smoothness of motion with spectral arc length of −3.18, covered area of 10.11 cm2, 1.54 mm spacing between 15 sweep trajectories, maximum translation of 27.99 mm, and time to finish of 3.11s.ConclusionsAutomatic modality improved the accuracy of scanning within a large workspace. The robotic capability provided better control to the user to define spacing resolution of scanning patterns.

Concordance of Solid Organ Biopsy Diagnoses With Hospital Autopsy and the Contribution of Biopsies to Death.

Biopsies of the liver, lung, and kidney are performed for many indications, including organ dysfunction, mass lesions, and allograft monitoring. The diagnosis depends on the sample, which may or may not be representative of the lesion or pathology in question. Further, biopsies are not without risk of complications. Autopsies are a resource for assessing the accuracy of biopsy diagnoses and evaluating possible complications. Herein, we aimed to compare liver, lung, and kidney biopsy diagnoses with those from autopsies conducted soon after the procedure and to assess the contribution of biopsy to mortality. A 28-year search of our database identified 147 patients who were autopsied after dying within 30 days of a liver, lung, or kidney biopsy. The concordance of the biopsy diagnosis with the autopsy findings was determined. Finally, medical records were reviewed to determine the likelihood that a biopsy contributed to the patient's death. The contribution of the biopsy to death was categorized as "unlikely," "possible," or "probable." Overall concordance between biopsy and autopsy diagnoses was 87% (128/147), including 95% (87/92), 71% (32/45), and 90% (9/10) for liver, lung, and kidney biopsies, respectively. Concordance was lower for biopsies of suspected neoplasms versus non-neoplastic diseases. Lung biopsy concordance was higher for wedge biopsy versus needle or forceps biopsy. A biopsy was determined to at least "possibly" contribute to death in 23 cases (16%). In conclusion, an autopsy is an important tool to validate liver, lung, or kidney biopsy diagnoses. Confirmation of biopsy diagnoses via post-mortem examination may be particularly valuable when patients die soon after the biopsy procedure. Furthermore, an autopsy is especially useful when patients die soon after a biopsy in order to determine what role, if any, the procedure played in their deaths. Though biopsy complications are uncommon, a biopsy may still contribute to or precipitate death in a small number of patients.

All-Body-Cavity (ABC)-scopy-An approach for a feasible method of minimally invasive autopsy to allow for postmortem tissue sampling in cases where a conventional autopsy is denied.

The decreasing autopsy numbers in many western countries have been partially attributed to the invasiveness of the autopsy, which causes relatives to decline postmortem examination. This issue has been addressed by developing methods of minimally or non-invasive autopsy, which could be shown to increase acceptance for autopsies. The aim of this study is to compare the All-Body-Cavity-scopy (ABC-scopy) to conventional autopsies for diagnostic accuracy. The ABC-scopy is an endoscopic approach for minimally invasive autopsy involving laparoscopic and thoracoscopic evaluation of the accessible organs, followed by excision biopsies of relevant organs and conspicuous findings. The method was performed in 10 cases on deceased patients scheduled for autopsy, each followed by a conventional autopsy. The results gathered from ABC-scopy through observation and histopathological evaluation provided an acceptable diagnostic accuracy in 9 out of 10 autopsies when compared to those of the conventional autopsy for diagnostic findings. The ABC-scopy is a feasible approach for minimally invasive autopsy that provides acceptable diagnostic value. Despite its minimally invasive nature, the procedure enables representative histology through providing large size excision biopsies from intraabdominal and thoracic organs, which is especially useful for examining disseminated diseases such as metastasized tumors.

Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment.

Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.

Indian society of organ transplantation: New Era

Dear Esteemed colleagues, I am writing this column after taking over as ISOT president being supported by the proactive executive committee. Former president Prof. Sunil Shroff had provided new initiatives in 2021–2022, which have gone above and beyond in leading by example with regard to team working, cross-specialty collaboration, and raising awareness of how the social determinants of health such as organ donation drive affect and save many lives. I congratulate his leadership for these endless efforts. Prof. Manisha Sahay editor-in-chief of the Indian Journal of Transplantation has commendably published every edition suitably representing the broad spectrum of scientific literature. As she demits editorship, I say a big thank you, as she hands over the reins of the journal to Prof. Narayan Prasad. As we are all aware of the lacunae in transplantation immunology, transplant-related infections, and appropriate transplant-related multiple organ biopsy interpretation, I convened a zoom meeting of Prof. Dolly Daniel (Immunologist), Prof. Priscilla Rupoli (Infectious disease), and Prof. Seethalakshmi (Pathologist) with Prof. Vivek Kute last week to form subcommittees. These three will work 24 × 7 through the website to give timely support to all transplant facilities across India. I express my thanks for their commitment. Having been the organizing chairman for ISOT 1997 and 2015 in Chennai, I understand how pressurized is our transplantation landscape. I request our trainee nephrologists, urologists, Pathologists, infectious disease people, other multi-organ transplant physicians, and surgeons to join the society to strengthen our society and be beneficiaries. The collaborative efforts undertaken by ISOT, the British Transplant Society, and the European Society of Transplantation on a mutually respectable platform will accelerate our efforts in terms of the exchange of knowledge. Short-term and long-term fellowship programs and other exchanges should be utilized to the best of our efforts. Our young members in the executive and membership are exemplary value to the society. They are an absolutely vital part of our commitment to encourage upcoming youngsters to develop an active role in future issues that matter to them in our influencing work. The pandemic greatly disrupted our work. Nevertheless, Prof. Vivek Kute and other colleagues put in extraordinary efforts to show the transplant community across the world of our challenges and solutions through publications. They deserve special appreciation. Although we lost some patients during the first and second waves, we gained much-desired experience in the management of our patients. As the misinformation and paucity of information and unnecessary hype created by some media demoralized our eminent doctors and uncalled punishment action by certain government authorities falling prey to misinformed advice, we have to stand together as a responsible body to take and deal with these challenges effectively. The discussion highlighting legal issues by Prof. Sanjay Agarwal along with ISN and facing the media in a previous incident was highly educative. We require a strong legal cell to protect our doctors. I also look forward to bidding for a future WCT in India. I take this opportunity to congratulate the three Indians Prof. Manikkam Suthanthiran, Dr. Gomathy Narasimhan, and Prof. Vivek Kute for receiving prestigious awards by TTS at the WCT in Buenos Aires, Argentina. They are the face of India. I wish you all a Happy New Year. Figure 1 is the picture of Prof. Krishna Menon, President BTS; Gabriel Oniscu, President ESOT; and myself.Figure 1: Gabriel Oniscu, Georgi Abraham, Krishnan Menon

Amyloidosis: What does pathology offer? The evolving field of tissue biopsy.

Since the mid-nineteenth century pathology has followed the convoluted story of amyloidosis, recognized its morphology in tissues and made identification possible using specific staining. Since then, pathology studies have made a significant contribution and advanced knowledge of the disease, so providing valuable information on the pathophysiology of amyloid aggregation and opening the way to clinical studies and non-invasive diagnostic techniques. As amyloidosis is a heterogeneous disease with various organ and tissue deposition patterns, histology evaluation, far from offering a simple yes/no indication of amyloid presence, can provide a wide spectrum of qualitative and quantitative information related to and changing with the etiology of the disease, the comorbidities and the clinical characteristics of patients. With the exception of cardiac transthyretin related amyloidosis cases, which today can be diagnosed using non-biopsy algorithms when stringent clinical criteria are met, tissue biopsy is still an essential tool for a definitive diagnosis in doubtful cases and also to define etiology by typing amyloid fibrils. This review describes the histologic approach to amyloidosis today and the current role of tissue screening biopsy or targeted organ biopsy protocols in the light of present diagnostic algorithms and various clinical situations, with particular focus on endomyocardial and renal biopsies. Special attention is given to techniques for typing amyloid fibril proteins, necessary for the new therapies available today for cardiac transthyretin related amyloidosis and to avoid patients receiving inappropriate chemotherapy in presence of plasma cell dyscrasia unrelated to amyloidosis. As the disease is still burdened with high mortality, the role of tissue biopsy in early diagnosis to assure prompt treatment is also mentioned.

Nanoparticle-mediated genome editing in single-cell embryos via peptide nucleic acids.

Through preimplantation genetic diagnosis, genetic diseases can be detected during the early stages of embryogenesis, but effective treatments for many of these disorders are lacking. Gene editing could allow for correction of the underlying mutation during embryogenesis to prevent disease pathogenesis or even provide a cure. Here, we demonstrate that administration of peptide nucleic acids and single-stranded donor DNA oligonucleotides encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to single-cell embryos allows for editing of an eGFP-beta globin fusion transgene. Blastocysts from treated embryos exhibit high levels of editing (~94%), normal physiological development, normal morphology, and no detected off-target genomic effects. Treated embryos reimplanted to surrogate moms show normal growth without gross developmental abnormalities and with no identified off-target effects. Mice from reimplanted embryos consistently show editing, characterized by mosaicism across multiple organs with some organ biopsies showing up to 100% editing. This proof-of-concept work demonstrates for the first time the use of peptide nucleic acid (PNA)/DNA nanoparticles as a means to achieve embryonic gene editing.

Diagnostic markers of hepatic steatosis in patients with chronic viral hepatitis C

Objective was to conduct a comparative analysis of routine clinical and laboratory parameters in two groups of patients with chronic viral hepatitis C (CHC) depending on the presence or absence of hepatic steatosis.Methods and materials. The observational retrospective cross-sectional study included 411 patients with CHC, of which 43.80 % were those with hepatic steatosis. The studied parameters were routine clinical and laboratory parameters, the viral genotype, as well as formalized results of a liver biopsy and ultrasound examination of the abdominal organs. To assess the differences between the two groups, the following were calculated: Pearson’s test, two-tailed Fisher’s test, Wilcoxon rank sum test, Spearman’s correlation coefficient, and partial correlation coefficient.Results. It was found that CHC patients with hepatic steatosis were older and had a higher body mass index (BMI) than patients without hepatic steatosis (p<0.01). Among patients with hepatic steatosis, the 3a genotype of the virus (p<0.001) and advanced stages of liver fibrosis (p<0.01) were more often detected, higher concentrations of hepatic transaminase (p£0.001) and iron (p<0 .01) in blood serum were observed, as well as higher liver (p<0.001) and pancreas (p<0.001) sizes on ultrasound than among patients without hepatic steatosis.Conclusion. Age, BMI, viral genotype, stage of liver fibrosis, ALT, AST, GGT, and iron levels, as well as liver and pancreas size are potential predictors of the presence of hepatic steatosis in CHC patients.

Weakly supervised learning for multi-organ adenocarcinoma classification in whole slide images.

The primary screening by automated computational pathology algorithms of the presence or absence of adenocarcinoma in biopsy specimens (e.g., endoscopic biopsy, transbronchial lung biopsy, and needle biopsy) of possible primary organs (e.g., stomach, colon, lung, and breast) and radical lymph node dissection specimen is very useful and should be a powerful tool to assist surgical pathologists in routine histopathological diagnostic workflow. In this paper, we trained multi-organ deep learning models to classify adenocarcinoma in biopsy and radical lymph node dissection specimens whole slide images (WSIs). We evaluated the models on five independent test sets (stomach, colon, lung, breast, lymph nodes) to demonstrate the feasibility in multi-organ and lymph nodes specimens from different medical institutions, achieving receiver operating characteristic areas under the curves (ROC-AUCs) in the range of 0.91 -0.98.

Prevalence of Monoclonal Gammopathy of Clinical Significance (MGCS) Among Patients with Monoclonal Gammopathies: Report from a Referral Center

Monoclonal gammopathies (MG) may be associated with a variety of syndromes due to the properties of the monoclonal protein, ectopic production of cytokines or other mechanisms. These syndromes may involve the kidneys, peripheral nerve, skin, eyes or other non-organ confined systemic syndromes. These disorders are usually associated with a nonmalignant or premalignant B-cell or plasma cell clone that does not fulfill the typical criteria of symptomatic myeloma or Waldenström's macroglobulinemia. These heterogeneous syndromes have attracted increasing attention and have been termed as "Monoclonal Gammopathy of Clinical Significance" (MGCS), however, their diagnosis remains challenging, requiring a high degree of suspicion or invasive target organ biopsies. Because of the difficulties in their recognition, it is not known how common these syndromes are among patients with monoclonal gammopathies. On the other hand, MG is a frequent finding: a recent prospective study in Iceland reported a prevalence of ~5% among subjects over the age of 40. Thus, the prevalence of MGCS may be significantly underestimated due to the heterogeneous phenotype, the difficulties in establishing the diagnosis and low degree of suspicion. In order to provide an estimate of the prevalence of MGCS among patients with known MG, we analyzed the database of a plasma cell dyscrasia referral center, in Athens, Greece. This is a prospectively maintained database which includes all patients with monoclonal gammopathies who are referred to our center for evaluation or treatment. Since AL amyloidosis is associated with a more aggressive clinical phenotype and requires prompt initiation of therapy, we evaluated these patients separately in our analysis. Because of an increasing interest in MGCS after 2010, and subsequent rising awareness and diagnostic sensitivity, we excluded earlier referrals and focused only on patients who were referred after 1/1/2010. The analysis included all patients who were referred for evaluation because of MG with or without concomitant symptoms or laboratory abnormalities. From 1/1/2010 to 31/12/2021, 3138 patients were referred for evaluation. The final diagnosis was MGUS or asymptomatic myeloma or asymptomatic WM in 1437 patients, symptomatic MM in 1145 patients, AL amyloidosis in 320 patients, symptomatic WM in 108 patients and a MGCS-related syndrome was diagnosed in 128 patients (4.1%). Among those with MGCS, the majority had either MGRS (n=51) or IgM-related neuropathy (n=58); other specific diagnoses included POEMS syndrome, Schnitzler's syndrome, necrobiotic xanthogranuloma or scleromyxedema, and other rare syndromes (TEMPI syndrome, IgM retinopathy, Clarkson's syndrome). Peripheral neuropathy with a concomitant MG was the most common co-existing condition among non-AL amyloidosis patients: 73% had IgM and 37% a non-IgM MG. A causal relationship between MG and neuropathy was established for 42% of those with non-IgM neuropathy (mainly due to POEMS syndrome). The median age of the MGCS patients was 64, not significantly different in clinical terms from that of patients with SMM/MGUS, AL amyloidosis, symptomatic MM and symptomatic WM (which was 65, 65, 67 and 70 years respectively). The baseline level of monoclonal immunoglobulin among MGCS patients was low (median 0.4 gr/dl) and significantly lower than in patients with MGUS/SMM/aWM (median 1.04 gr/dl). The median BM infiltration by clonal cells in patients with MGCS was 10%, and was 7% in the MGUS/SMM group, 15% in patients with AL amyloidosis, 50% in patients with symptomatic MM and 40% for patients with symptomatic WM. Most patients with MGCS received anticlonal therapy; other non-clone targeting therapies were used in patients with Schnitzler's syndrome and Clarkson's disease. A significant proportion of patients with IgM-related neuropathy received only supportive therapy. In conclusion, MGCS was found in ~4% of patients with MG in a plasma cell dyscrasia referral center. The establishment of MGCS diagnosis requires high degree of clinical suspicion due to their rarity and highly heterogeneous clinical presentation. Despite the bias associated with the analysis from a referral center, given the frequency of MG in the general population, there is probably a significant number of patients with MGCS who remain underdiagnosed and may suffer from complications associated with an otherwise non-malignant plasma cell dyscrasia.

Sarcoidosis and Its Dermatological Manifestations: A Narrative Review.

Sarcoidosis is an enigma diagnosed by ruling out other etiologies of granulomatous inflammation. The multisystem manifestations of sarcoidosis and the clinical polymorphism pose a diagnostic challenge to all physicians. The skin is the most commonly affected organ after the lungs in sarcoidosis. Dermatological manifestations can appear before, during, or after systemic involvement, and the type of skin lesion can have prognostic significance. Also, a biopsy of skin lesions is less invasive and more accessible to perform than a biopsy of visceral organs. Thus, in certain ways, cutaneous manifestations can aid in the diagnosis and prognosis of systemic disease. This article has focused on the frequently encountered skin lesions of sarcoidosis along with their prevalence, clinical features, and management.

Emergency Vaccination as a Control Strategy against Sheeppox Outbreak in a Highly Susceptible Population.

Simple SummarySheeppox is an emerging disease in different parts of the world with a huge impact on animal health and production. Emergency vaccination might be an effective strategy to overcome this disease. In this study we characterized in detail an outbreak of sheeppox in a susceptible naive sheep population in Egypt. The local and the systemic signs as well as postmortem and the histopathological findings of the disease were confirmed. We also compared the efficacies of two commercial sheeppox vaccines (Romanian strain and RM-65 vaccines). Our results confirmed the superiority of the RM-65 vaccine compared to the Romanian strain vaccine in protecting the animals. Furthermore, we highlighted the validity of emergency vaccination to control a sheeppox outbreak.This study aimed to investigate a sheeppox outbreak in a highly susceptible naive sheep population in Kharsit village, Gharbia Governorate, Egypt. Moreover, to compare commercial sheeppox vaccines, the Romanian strain and RM-65 vaccines, as emergency vaccination against sheeppox under field conditions. In December 2018, a sheeppox outbreak occurred in a flock of 65 sheep upon the purchase of an apparently healthy ewe from outside the village. This ewe showed a systemic disease with cutaneous lesions after a few days, thereafter more cases began to appear. Cutaneous lesions in other sheep in the flock in the form of macules, papules, and scabs were common in wool-less areas of the body, in addition to fever and respiratory disorders. Postmortem findings revealed the congestion of visceral organs with apparent gross pathology of the lung. Biopsies of cutaneous lesions and visceral organs were collected, and sheeppox was identified by histopathology and transmission electron microscopy, which showed the existence of sheeppox cells and intracytoplasmic brick-shape sheeppox virions. The Romanian strain and RM-65 vaccines were used for the emergency vaccination for two different groups of animals and the third group was left as a control group. Serum samples were collected before vaccination as well as 21 days post-vaccination, and serum protein fractionation analysis was performed for all groups. The outbreak ended after 2.5 months, the cumulative incidence was 66.2%, and the overall case fatality was 51.1%. There was significantly higher protection against sheeppox infection and mortalities among RM-65 vaccine immunized group compared to Romanian strain vaccine-immunized animals at p < 0.05. RM-65-vaccinated animals did not show sheeppox cases or mortalities, compared to Romanian strain-vaccinated animals, which had mild pox signs in 78% of animals and case fatality of 35.7%. The serum protein analysis also indicated the superior performance of the RM-65 vaccine; it increased the level of α1-globulin and β-globulin compared to the Romanian strain, which increased the level of β-globulin only. The current study shows a better performance of the tested RM-65 than the Romanian strain vaccine for emergency vaccination against sheeppox under field conditions. These findings point to the validity of emergency vaccination against sheeppox and the importance of the comparative field evaluation of vaccines; however, wide-scale studies are required for further evaluation. Future investigation of whether the Romanian strain itself or vaccine-production-related issues are responsible for these findings is required.

Testicular Germ Cell Tumours-The Role of Conventional Ultrasound.

Simple SummaryTesticular tumours are the most common cancer found in young men, and germ cell tumours account for the majority. This article describes the use of conventional ultrasound in germ cell tumours and how to perform the ultrasound, including how to improve patient position and scanning technique. The classification of germ cell tumours is also provided, and the salient features of different types of tumour are described. Some pitfalls and difficulties of ultrasound are discussed, as well as other uses of ultrasound in this group of patients.Testicular tumours are the most common tumours found in young males and germ cell tumours account for 95% of testicular tumours. Ultrasound is the first-line radiological investigation for imaging of the testis. This article outlines how to undertake an ultrasound examination, including optimal patient position, scanning technique and imaging parameters. Classification of germ cell tumours is provided, and salient imaging features of different tumours are described. Difficulties and pitfalls of ultrasound are described, including tumours found after a trauma presentation, orchitis causing diagnostic difficulties and imaging of small testicular lesions. Other uses of ultrasound are outlined, including looking for a primary testicular tumour following the discovery of retroperitoneal lymph nodes, imaging when tumour-makers increase, local recurrence in the scrotum, and for solid organ biopsy in metastatic disease. Conclusion: Ultrasound remains the first-line of investigation for imaging of the testis, and conventional ultrasound still plays a large role in imaging. On ultrasound alone, accurate morphological characterisation of tumours remains a challenge, despite the imaging features that can be seen in different tumour types. Therefore, histology following orchidectomy of a germ cell tumour remains the gold standard for accurate tumour characterisation.

A Focus on Waldenström Macroglobulinemia and AL Amyloidosis.

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma that is characterized by the overproduction of an IgM monoclonal protein. It may cause adenopathy, hepatomegaly, splenomegaly, as well as other disease-related complications such as cold agglutinin anemia, cryoglobulinemia, hyperviscosity, and neuropathy. While light chain amyloidosis in patients with WM only occurs in about 10% of patients, it is important that advanced practitioners are able to recognize concurrent AL amyloidosis, which will affect the patient's treatment trajectory. Diagnosis of WM with AL amyloidosis is based on bone marrow biopsy and a fat pad biopsy. If AL amyloidosis is suspected, the bone marrow and fat pad biopsy should undergo Congo red staining. If it is negative, and there is a strong suspicion of AL amyloidosis, then an organ biopsy can be considered. Treatment of WM uses rituximab-based therapy in combination with a variety of other agents, including proteasome inhibitors, alkylating agents, and BTK inhibitors. Treatment of light chain amyloidosis uses bortezomib as the backbone of therapy and can be administered with cyclophosphamide, dexamethasone, and now daratumumab, which was recently approved. Waldenström macroglobulinemia and light chain amyloidosis are both rare diseases and can lead to a variety of disease-related complications. Fortunately, many options exist for both diseases. This article will highlight a case of WM with amyloidosis and a case of a patient with relapsing WM with considerations for advanced practitioners managing this patient population.

Abstract 1724: Pancancer evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 in SHIVA-01 trial patients with different biopsy sites and histological types

Abstract Background: Immunologic characterization of tumors and their microenvironments had been proposed based on the combination of PD-L1 expression and the presence of tumor-infiltrating lymphocytes (TILs). This study aims to investigate in metastatic samples from patients with cancer, the distribution of TILs and expression of PD-L1 using Combined Positive Score (CPS), Tumor Proportion Score (TPS), as well as TILs. These variables were further evaluated in paired primary and metastatic samples and correlated with clinical outcome. Patients and methods: 550 pan-cancer patients of SHIVA01 trial (NCT01771458) with available contributive FFPE sample from a metastatic biopsy and 111 paired primary and metastatic samples were evaluated for TILs. The 550 metastatic specimens were biopsies from different anatomical sites subdivided into 7 groups: liver biopsies (n=179; 33%), visceral organ biopsies (n=92; 17%), lung biopsies (n=89; 16%), lymph node biopsies (n= 88; 16%), cutaneous biopsies (n=53; 10%), soft tissue biopsies (n=48; 9%) and brain biopsy (n=1; 0.2%). PD-L1 expression was assessed by Immunohistochemistry using the 22C3 antibody clone (Merck &amp; Co) and quantified using two scores: CPS and TPS, in 494 metastatic tumors and in 77 paired primary and metastatic tumors patients with contributive immunohistochemistry. The correlations of TILs and PD-L1 expression with clinical outcomes are ongoing. Results: In metastatic samples, we found no difference in TILs distribution according to histological subtype, primary system or biopsy site with a median of 10% [range: 0%-70%]. A significant decrease in the median percentage of TILs was found in metastases in comparison to their paired primary lesions (20% [5%-60%] versus 10% [0%-40%], p&amp;lt;0.0001). PD-L1 expression was homogenous in all metastatic tumors independently of primary system or biopsy site (median TPS = 2% ; CPS = 0 n=218, CPS≥1 n=265 ; p=0.056). There was a strong association between TPS count and histological subtypes (p=0.015) that was not observed with CPS (p=0.23). In paired primary/metastatic samples, we did not observe any changes in the CPS and TPS scores (p&amp;gt;0.3 for both). Conclusion: We show that metastatic sites are less infiltrated with lymphocytes as compared to their paired primary lesions independently of the initial primary tumor site, histological type or biopsy site. PD-L1 expression was similar in paired primary and metastatic samples. Citation Format: Zakhia El Beaino, Célia Dupain, Grégoire Marret, Xavier Paoletti, Laëtitia Fuhrmann, Charlotte Martinat, Ivan Bièche, Christophe Le Tourneau, Maud Kamal, Anne Vincent-Salomon. Pancancer evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 in SHIVA-01 trial patients with different biopsy sites and histological types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1724.

ANALYSIS OF OBTAINING AN IMAGE WITH THE TOMOGRAPH

CT scans vary from manufacturer to manufacturer. There are several generations of CT. The concept of CT generation is not so much related to the time of its birth, but to the use in the scanner of the type of motion of the emitter-detector system. The generation number (first, second, third, fourth, etc.) is related to the type of tube-detector system design. Three types of scanners are now available: third, fourth and fifth generation. The life of the first generation of CT was fleeting: the duration of the scan did not suit – about 20 minutes. and the computer reconstruction of the image took too long. Only the brain could be examined on such devices. As for the human body, the image turned out blurry, blurred. But the process of improvement continues. Today, research is being conducted on fourth- and fifth-generation devices. They have not one, but many X-ray emitters, up to 200. It uses a very powerful processor with high-speed information processing – up to 10 million operations per second. As a result, the scan time was reduced to 40-50 milliseconds. It is now possible (here is a scientific idea!) To see on the telemonitor the reduction of certain transverse layers of the heart 1-2 millimeters thick. At spiral CT in the course of research with simultaneous constant rotation of system “tube – detectors” the table constantly moves and thus there is a spiral movement of a fan-shaped beam through a patient’s body. Spiral CT makes it possible to examine the anatomical region in one period of respiratory arrest, and the thickness of the reconstructed layer is not related to the original width of the tomogram. Obtaining thin conjunctival sections, which are tightly arranged in a spiral, allows you to get three-dimensional reconstructions. In combination with intravenous bolus contrast and subtraction data processing, CT angiograms can be obtained, which reproduce images of large vessels. In recent years, multispiral (multislice) CT has been used, which is based on the principles of imaging as in spiral CT, but due to multi-row detectors for full rotation of the system “tube detectors” can display more than one slice (currently from 2 to 16 images). This has made it possible to perform studies of the heart, study a large anatomical area, such as the lungs, thin sections in one breath hold, and significantly improve the quality of multiplanar and three-dimensional reconstructions. In electron beam tomography, the source of X-rays is a large electron gun with several massive parallel anode targets located in semiconductor rings around the patient. The intense anode beam is directed along the tungsten anode rings. The electron beam thus obtained passes through the patient’s body and is received by a fixed array of detectors. This achieves a high tomography rate, which is sufficient for the study of a moving heart: clearly delineated images can be obtained without the use of synchronization with the ECG. With the help of electron-beam tomography it is also possible to perform CT angiography and construction of high-quality three-dimensional reconstructions. Thus, modern medicine is impossible without CT. For example, in neurology, computed tomography, in addition to skull bones, well identifies the ventricles of the brain, venous sinuses, subarachnoid cisterns, interhemispheric fissure, cortex, basal nodes, inner capsule, trunk, cerebellum and other structures. The radiation load does not exceed the level usual for X-ray examination. At the same time, CT scans provide 100 times more information about the brain than conventional skull x-rays. But its importance is not limited to use only for the diagnosis of various diseases. Under the control of CT perform punctures and directed biopsy of various organs and pathological foci. The role of CT in the control of conservative and surgical treatment of patients is extremely important. CT is a valuable method of accurate localization of tumors and directing the radiation source to the focus when planning radiation treatment of malignant tumors.

Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment.

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)." Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5months. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.

Clinical features and diagnosis of neurosarcoidosis – review article

Neurosarcoidosis affects 5–26% of patients with systemic sarcoidosis and can be the first or only manifestation of the disease. Neurosarcoidosis can affect any part of the nervous system with heterogeneous clinical manifestations and imaging appearances that overlap with many infectious, inflammatory, and neoplastic disorders, making its diagnosis challenging. In the absence of a reliable biomarker to confirm neurosarcoidosis, the diagnosis is based on identifying a compatible clinical and imaging profile and identifying pathological evidence of non-caseating granulomas by biopsy of other organs or, if needed, in the nervous system, with the exclusion of other causes of granulomatous disease and possible neuroinfectious and neuroinflammatory disorder mimics. This review focuses on the clinical features of neurosarcoidosis with an emphasis on the recognition of the main presentation phenotypes and the initial diagnostic approach and differential diagnosis of neurosarcoidosis.

Modern concepts of primary systemic AL-amyloidosis: the viewpoint of a gastroenterologist

The purpose of the review is to present an analysis of modern literature data on the pathogenesis, diagnosis and therapy of primary systemic amyloidosis of immunoglobulin light chains (AL-amyloidosis), to reveal the features of gastroenterological manifestations of the disease. AL-amyloidosis is caused by overproduction of immunoglobulin light chains by a clone of plasma cells located in the bone marrow, followed by the formation of amyloid.Deposition of amyloid in target organs (heart, kidneys, liver, gastrointestinal tract, peripheral and autonomic nervous systems, soft tissues) is accompanied by direct and indirect cytotoxic effects on organs and tissues. Gastrointestinal manifestations of AL-amyloidosis include liver damage, gastrointestinal bleeding, pseudo-obstruction of the small intestine and colon, the appearance of polyp-, diverticul-, tumor-like formations, malabsorption, impaired motility of the gastrointestinal tract, protein-losing gastropathy. Liver damage in patients with AL-amyloidosis, as a rule, is accompanied by minimal clinical manifestations, an increase of the level of alkaline phosphatase without any other reasons for this change. A detailed analysis of the Mayo Clinic’s practical guidelines for the diagnosis and treatment of AL-amyloidosis is presented. Diagnosis of gastrointestinal AL-amyloidosis is based on histomicroscopic analysis of biopsies of target organs with Congo red and subsequent examination in polarized light; mass spectrometry is the gold standard of diagnostic. Modern pharmacotherapy of AL-amyloidosis includes a combination of high-dose chemotherapy with monoclonal antibodies, proteasome inhibitors, cytostatics, hormones, as well as performing autologous stem cell transplantation. Correction of gastroenterological manifestations of the disease is based on the symptomatic therapy. Life expectancy of patients with AL-amyloidosis is determined by several prognostic models; the Boston University model, based on the definition of two markers, is most convenient for clinical use.

Variability in personal protective equipment in cross-sectional interventional abdominal radiology practices.

PurposeTo determine institutional practice requirements for personal protective equipment (PPE) in cross-sectional interventional radiology (CSIR) procedures among a variety of radiology practices in the USA and Canada.MethodsMembers of the Society of Abdominal Radiology (SAR) CSIR Emerging Technology Commission (ETC) were sent an eight-question survey about what PPE they were required to use during common CSIR procedures: paracentesis, thoracentesis, thyroid fine needle aspiration (FNA), superficial lymph node biopsy, deep lymph node biopsy, solid organ biopsy, and ablation. Types of PPE evaluated were sterile gloves, surgical masks, gowns, surgical hats, eye shields, foot covers, and scrubs.Results26/38 surveys were completed by respondents at 20/22 (91%) institutions. The most common PPE was sterile gloves, required by 20/20 (100%) institutions for every procedure. The second most common PPE was masks, required by 14/20 (70%) institutions for superficial and deep procedures and 12/12 (100%) institutions for ablation. Scrubs, sterile gowns, eye shields, and surgical hats were required at nearly all institutions for ablation, whereas approximately half of institutions required their use for deep lymph node and solid organ biopsy. Compared with other types of PPE, required mask and eye shield use showed the greatest increase during the SARS-CoV-2 pandemic.ConclusionPPE use during common cross-sectional procedures is widely variable. Given the environmental and financial impact and lack of consensus practice, further studies examining the appropriate level of PPE are needed.Graphical abstract