Endoscopic ultrasound-guided deep and large biopsy for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies

AIM: To assess the diagnostic yield and safety of adeep and large biopsy technique under the guidance of endoscopic ultrasound(EUS) for diagnosis of gastric infiltrating tumors with negative malignant endoscopy biopsies.METHODS: From January 2009 to March 2014, 36 patients in whom gastric infiltrating tumors had been diagnosed by EUS received negative results for malignancy after endoscopic biopsies. The deep and large biopsy technique combined bite-on-bite technique with or without endoscopic mucosal resection(EMR) to obtain submucosal tissue from lesions. EUS was used to select the appropriate biopsy sites. If the lesion protruded into the cavity, EMR was performed for removal of the overlying mucosa and then bite-onbite technique was conducted in the resected area to obtain submucosal tissue. If the lesion appeared to be flat or was difficult to lift by injection, the bite-on-bite technique was directly used.RESULTS: Twenty-eight of the 36 patients were treated by EMR followed by bite-on-bite technique, while 8 patients only underwent bite-on-bite technique. Histological results showed 23 of the 36 lesions were poorly differentiated adenocarcinomas, 2 diffuse large B cell lymphomas, 4 mucosa-associated lymphoid tissue-type lymphomas, and 7 undiagnosed. The deep and large biopsy technique provided a definitive and conclusive diagnosis in 29(80.6%) of the 36 patients. The 12 gastric linitis plastica and 6 lymphoma patients received chemotherapy and avoided surgery. Minor oozing of blood in 2 mucosal resection wounds was managed by argon plasma coagulation and in 5 cases after deep biopsies by epinephrine(0.001%). Neither severe hemorrhage nor perforation occurred in any patient.CONCLUSION: The deep and large biopsy technique is superior to ordinary endoscopic biopsy for achieving an accurate diagnosis of gastric infiltrating tumors.This procedure guided by EUS is an effective and safe diagnostic method for gastric infiltrating tumors in which endoscopic biopsy results were negative for malignancy.

Wilson disease:Histopathological correlations with treatment on follow-up liver biopsies

AIM:To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease(WD)patients.METHODS:We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies.Demographic,clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy.RESULTS:Time to repeat biopsy ranged from 2 to 12 years.Six patients(non-progressors)showed stable hepatic histology or improvement.In one case,we observed improvement of fibrosis from stage 2 to 0.Six patients(progressors)had worsening of fibrosis.There was no significant correlation between the histological findings and serum aminotransferases or copper me-tabolism parameters.The hepatic copper concentration reached normal levels in only two patients:one from the non-progressors and one from the progressors group.The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy(4 years),and 0.25 between the second and the third(3 years).In the progressors group,the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and,0.6 fibrosis units between the second and third biopsy.CONCLUSION:The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.

Cytopathologic diagnosis of fine needle aspiration biopsies of thyroid nodules

Fine-needle aspiration(FNA) cytology is an important diagnostic tool in patients with thyroid lesions.Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules.However cases with indeterminate cytological findings still remain a matter of debate.In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules.A review of the English literature was conducted,and data were analyzed and summarized and integrated from the authors' perspective.The main purpose of thyroid FNA is to identify patients with higher risk for malignancy,and to prevent unnecessary surgeries for benign conditions.The Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA specimens.This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases.In conclusion,patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%.

Pancreatic cancer: Are 'liquid biopsies' ready for prime-time?

Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells(CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA(ct DNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ct DNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.

Pathological,immunohistochemical and microbiologicalal analysis of lacrimal sac biopsies in patients with chronic dacrocystitis

AIM:To analyze cases of obstruction of the nasolacrimal duct which creates a fertile environment for secondary bacterial Infection and can result in dacryocystitis,which is a constant threat to cornea and orbital soft tissue and a potential source of endophthalmitis following intraocular surgery.The majority of obstructions of the lacrimal excretory outflow system are acquired ones occurring in adulthood and involving the distal parts of the system.Acquired obstruction may be primary/idiopathic or secondary to a wide variety of infectious,inflammatory,traumatic,mechanical,toxic or neoplastic causes mimicking idiopathic inflammation.These cases are treated by dacryocystorhinostomy(DCR).METHODS:The present study was conducted to determine the histopathologic,immunohistochemical and current microbiologic characteristics of lacrimal sac specimens in patients undergoing external dacryocystorhinostomy.RESULTS:Non-specific lacrimal sac pathology was present in all 33 cases and 81.8%of the cases showed moderate chronic inflammation with a chronic inflammatory score(CIS)ranging between 4 and 6,whereas 12.12%showed severe inflammatory changes with a CIS of 7.Mild degree of inflammation was seen in6.06%with a CIS of 3.The total prevalence of grampositive,gram-negative,and culture-negative samples were 59.4%,37.5%,and 3%respectively.CONCLUSION:Non-specific chronic inflammation withfibrosis is indeed the most commonly reported histopathological finding in lacrimal sac wall biopsy specimens.

A mini-review on factors and countermeasures associated with false-negative sentinel lymph node biopsies in breast cancer

Sentinel lymph node biopsy （SLNB） is a new surgical technique for local axillary lymph nodes （ALNs） of breast cancer. Large-scale clinical trials have confirmed that undergoing SLNB and ALN dissection （ALND） showed no significant difference for sentinel lymph node （SLN）-negative patients in terms of disease-free survival, overall survival and recurrence-free survival. However, false-negative results are still the main concern of physicians as well as patients who undergo SLNB instead of ALND. The American Society of Breast Surgeons established a task force to suggest acceptable standards for SLNB. In 2000, the task force recommended that the identification rate for SLNB be 85% or higher and the false-negative rate be 5% or lower. This review focuses on clinical factors （tumor volume, multifocal/multi-center cancers, neoadjuvant chemotherapy and skip metastasis）, tracer techniques and pathological factors affecting SLNB and explores methods for reducing the false-negative rate.

Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.

Computer-aided morphometry of liver inflammation in needle biopsies

AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation.METHODS: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation,and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent.RESULTS: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%.CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.

Evaluation of routine biopsies in endoscopic screening for esophagogastric junction cancer

AIM: To explore whether routine biopsies at the high incidence spot of esophagogastric junction (EGJ) cancer are justified in endoscopic screening.

The Use of PCA3 Can Reduce the Number of Prostate Biopsies Performed in a Community-Based Urologic Practice

Purpose: It is now generally accepted that PSA screening identifies many prostate cancers that are low-risk and may not need treatment. PCA3 is a prostate cancer-specific marker with improved diagnostic accuracy when compared with PSA in research studies. It remains unknown whether PCA3 testing can reduce the unnecessary diagnosis and treatment of prostate cancer in routine practice. We evaluated whether the use of PCA3 in clinical practice decreases the number of biopsies being performed in response to PSA testing. Methods: 64 consecutive patients undergoing PCA3 measurement in a single community-based urology practice were analyzed for rates of biopsy performance and prostate cancer detection. Results: Median PSA was 5.0 (range: 0.4 - 38.6) and 50% had undergone prior biopsy without evidence of cancer. Median PCA3 score was 13.6 (range: 1.6 - 133.0) with 14 patients having an elevated PCA3 (>35). Prostate biopsy was avoided in 50 of 64 patients (78%). Of the 11 patients undergoing biopsy for abnormal PCA3, 7 had prostate cancer (64%). At >2-year median follow-up, 39 of the remaining 50 patients (78%) avoided subsequent biopsy. Only 5 prostate cancers were diagnosed during follow-up. Conclusions: When used in routine clinical practice, PCA3 appears to reduce the number of biopsies being performed in response to elevated PSA. Given the increasing interest in strategies to reduce unnecessary prostate cancer diagnosis and treatment, this FDA-approved and widely-available molecular test appears to achieve these goals. Further testing will clarify the role of PCA3 in initial and subsequent prostate cancer screening paradigms.

Electronic Synoptic Reporting of Thyroid Nodules: Potential for Reduction in Number of Patients Undergoing Thyroid Nodule Biopsies

Purpose: The objective of the study was to design and implement an electronic synoptic report for thyroid sonography that incorporates the thyroid imaging reporting and data system (TIRADS) and assess potential for reducing unnecessary fine needle aspiration biopsies (FNAB) of thyroid nodules. Methods: The electronic synoptic report was developed using a relational database based on elements from TIRADS and a multidisciplinary consensus statement for thyroid reporting. A retrospective analysis of 138 patients with previously reported thyroid sonographic exams was evaluated for the presence of these elements. The electronic synoptic report calculates the TIRADS score and generates a formal report. Using the TIRADS score the potential decrease in unnecessary FNAB was estimated. Results: Key TIRADS elements were variously reported ranging from 43% for the thyroid nodule’s architecture as solid or cystic. Thyroid nodule echogenicity and calcification was commented in 27% and 23%, respectively. Other features of the TIRADS score were commented in 0% to 8% of the official reports. Estimated reduction for potentially reduced need for FNAB was 34.5%. Conclusions: This study is the first implementation of synoptic reporting using a relational database for sonography of thyroid nodules. Implementation of an electronic standardized synoptic reporting system may facilitate more accurate, and more comprehensive reporting for thyroid ultrasound scanning of thyroid nodules. The use of TIRADS was estimated to be able to potentially reduce the need for FNAB which was significant.

Obtaining research biopsies during pediatric colonoscopy: Safety and adverse events

AIM: To investigate the safety profile of acquiring additional intestinal biopsies for research purposes in children undergoing a medically indicated colonoscopy. METHODS: A retrospective review of 122 pediatric patients who underwent colonoscopy over a 9 mo time period was completed. 38/122 participants consented to a research study in which 4 additional biopsies were obtained, in addition to routine biopsies. The outcomes after colonoscopy were measured in the research participants, and compared to 84 control participants who did not consent for the study. Groups were compared with regard to number of biopsies obtained, underlying diagnosis, and both serious and minor adverse outcomes. Data was collected including: age, gender, race, indication, diagnosis, number of biopsies obtained per case and post procedure adverse events. Medical records were reviewed and a questionnaire was completed by each of the ten gastroenterologists who performed procedures during the study. Physicians were asked about individual patient outcomes to ensure that all adverse events, such as perforation, excessive bleeding, infection, and minor gastrointestinal outcomes, were captured and included.RESULTS: The research group had more biopsies obtained(mean = 13.58 ± 4.21) compared to controls(mean = 9.33 ± 4.40), P ≤ 0.0001, however there was no difference in adverse events. Serious outcomes, defined as perforation, bleeding and infection, did not occur, in either group. As such, the relationship between serious adverse events and number of biopsies obtained was not determined. Minor gastrointestinal outcomes, such as abdominal pain, diarrhea or vomiting, were reported in 21 patients(8 research participants and 13 control participants) however the incidence of minor gastrointestinal outcomes between the two groups did not vary significantly, P = 0.45. Additionally, the meannumber of biopsies obtained in patients who had a minor outcome(mean = 12.1 ± 0.77), compared to those with no adverse outcome(mean = 10.34 ± 0.5), revealed no statistical difference between the groups(P = 0.12), suggesting that number of biopsies is not associated with incidence of minor adverse events.CONCLUSION: Patients participating in research requiring acquisition of additional biopsies for research purposes alone, are not at an increased risk of adverse outcomes.

Value of macrobiopsies and transanal endoscopic microsurgery in the histological work-up of rectal neoplasms:A retrospective study

To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODSPatients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm. RESULTSOne hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100. CONCLUSIONThe step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%.

Accuracy between clinical and radiological diagnoses compared to surgical orbital biopsies

AIM:To assess the concordance between diagnosing orbital lesions by clinical examination,orbital imaging,and histological evaluation,in order to help guide future research and clinical practice.METHODS:A retrospective analysis was undertaken at a large regional tertiary referral centre of all surgical orbital biopsies performed over a 5-year period,from 1st January 2015 until 31st December 2019.Accuracy and concordance between clinical,radiological and histological diagnoses are reported as percentage sensitivity and positive predictive value.RESULTS:A total of 128 operations involving 111 patients were identified.Overall,sensitivities of 47.7%for clinical and 37.3%for radiological diagnoses were found when compared to the histological gold standard.Vascular lesions that have characteristic clinical and radiological features had the highest sensitivity at 71.4%and 57.1%,respectively.Inflammatory conditions showed the lowest sensitivity in both clinical(30.3%)and radiological(18.2%)diagnoses.The PPV for inflammatory conditions were 47.6%for clinical and 30.0%for radiological diagnoses.CONCLUSION:Accurate diagnoses are difficult to reach by relying on clinical examination and imaging alone.Surgical orbital biopsy with histological diagnosis should remain the gold standard approach for definitively identifying orbital lesions.Although larger scale prospective studies would help further refine concordance and guide future research avenues.

Immunofluorescence on paraffin embedded renal biopsies:Experience of a tertiary care center with review of literature

AIMTo describe the technique of immunofluorescence on paraffin embedded tissue sections and discuss the po-tential pitfalls with an in depth review of literature.METHODSImmunofluorescence is integral to diagnostic renal pa-thology. Immunofluorescence on paraffin embedded renal biopsies （IF-P） after enzyme treatment has been described in literature, however has not found widespread use in renal pathology laboratories. In our laboratory proteinase K digestion of paraffn embedded renal biopsy material was standardized and applied prospectively in cases where immunofuorescence on fresh frozen tissue was non contributory or not possible. Diagnostic utility was assessed and in a cohort of cases comparison of intensity of staining with routine immunofuorescence was performed.RESULTSOver the 5-year study period, of the 3141 renal biopsies received IF-P was performed on 246 cases （7.7%） and was interpretable with optimal digestion in 214 cases （6.8%）. It was of diagnostic utility in the majority of cases, which predominantly included glomerular disease. Non-diagnostic IF-P was found in membranous nephropathy （2 of 11 cases）, membranoproliferative glomerulonephritis （2 of 32 cases）, lupus nephritis （1 of 25 cases）, post infectious glomerulonephritis （1 of 11 cases） and chronic glomerulonephritis （3 of 8 cases）. Comparing cases with both routine IF and IF-P, 35 of 37 showed either equal intensity or a minor difference in intensity of staining（1＋） for the diagnostic immunoglobulin/complement. Technically assessment of immunofluorescence on the paraffin embedded tissue was found to be easier with clearly observed morphology, however a false positive staining pattern was observed in under-digested tissue. CONCLUSIONAs a “salvage” technique, immunofuorescence on paraffn embedded renal biopsies is of great diagnostic utility, however not without pitfalls.

Gastric pseudolipomatosis, usual or unusual? Re-evaluation of 909 endoscopic gastric biopsies

Microvesicular pneumatosis intestinalis, also called 'pseudolipomatosis' for resembling fatty infiltration, is characterized by the presence of small gas voids in the gastrointestinal wall, especially in mucosa. These voids are not lined with epithelia. There are few reported cases about colon, duodenum and skin. Because there is only one case report about pseudolipomatosis in the stomach, we reevaluated 909 endoscopic biopsies taken from gastric corpus to check the presence of pseudolipomatosis. We determined pseudolipomatosis foci in 3 percent (n=27) of biopsies. In two cases there were pseudolipomatosis foci in endoscopic biopsies having otherwise normal histologic findings, while there were pseudolipomatosis foci in endoscopic biopsies of 25 patients with gastritis. H pylori was found in 85 % of biopsies having pseudolipomatosis foci. In this study, we presented some histopathologic characteristics of pseudolipomatosis seen in gastric mucosa.

Appropriate number of biliary biopsies and endoscopic retrograde cholangiopancreatography sessions for diagnosing biliary tract cancer

BACKGROUND Biliary ductal cancer(BDC) is a lethal disease; however, diagnosing BDC is challenging. Biliary biopsies are performed to pathologically diagnose BDC, but the appropriate parameters for biliary biopsy [number of biliary biopsies, number of endoscopic retrograde cholangiopancreatography(ERCP) sessions, etc.] are unknown.AIM To clarify what constitutes an adequate method for biliary biopsy.METHODS In total, 95 patients who underwent endoscopic biliary biopsy without choledochoscopy and who were pathologically diagnosed with BDC were enrolled in this study. The patients were divided into two groups. Seventy-six patients who were diagnosed by biliary biopsy were defined as the positive group(P group), and nineteen patients who were not diagnosed by biliary biopsy were defined as the negative group(N group). The patient characteristics and ERCP-related procedures were compared between the P and N groups.RESULTS The numbers of ERCP sessions and biliary biopsies were significantly different between the two groups [ERCP sessions(one/two), P group 72/4 vs N group15/4, P value = 0.048; number of biliary biopsies, P group 2(1-6) vs N group 2(1-7), P value = 0.039]. In a multivariate analysis, fewer than 2 ERCP sessions was an independent factor influencing the positivity of the biliary biopsies.CONCLUSION This study clarified that ERCP and biliary ductal biopsy should only be performed once. If biliary cancer is not pathologically diagnosed after the first ERCP session, other methods(Endoscopic ultrasonography-guided fine needle aspiration or choledochoscopy-guided biliary ductal biopsy) should be employed.

Liquid biopsies in cancer

Liquid biopsy,the detection of biomarkers from body fluids,has been widely used on circulating tumor cells(CTCs),circulating tumor DNA(ctD NA),circulating tumor microRNA,exosomes and other kinds of molecular characterization.Cancer,a series of comprehensive mechanisms,presents in different molecular forms that could be used in clinic for diagnosis,treatment,drug monitoring and prognosis judgement via liquid biopsies.Liquid biopsies are available to tumor heterogeneity,resistance,progression and metastases in clinic.Technologies for detection and analysis was improving for the obvious limitation of liquid biopsies,that leads the future directions.In this review,we provided critical views of liquid biopsies on cancer,including different methods of liquid biopsies and applications of liquid biopsies in current clinical trials and practice.

Incidental seminal vesicle amyloidosis observed in diagnostic prostate biopsies--are routine investigations for systemic amyloidosis warranted？

Seminal vesicle （SV） amyloidosis is a well-documented histological entity, but it is observed infrequently. Its incidence is on the rise, which is probably related to the increasing use of prostate biopsies to investigate patients with elevated serum prostate-specific antigen levels. Here, we report seven cases of incidental SV amyloidosis over a 3-year period and consider their relationship to the previously suggested aetiological factors. Based on our series, we conclude that incidental localized SV amyloidosis observed in diagnostic prostate biopsies does not warrant formal investigations for systemic amyloidosis.

THE CHANGES OF BONE VOLUME AND TURNOVER IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS：A REPORT OF 293 BONE BIOPSIES

bone biopsies of ooteoporosis in postmenopausal women were analyzed. The results showed that the mean ttabecular bone volume was(10.6 ± 5. 47)%, which is 29'3% less than the low value of normal range(15%).There were 186 (63. 5%)cases in normal turnover,75(25.6 %)cases in high turnover,and 32 (10.9%)tases in low turnover.In comparison with the normal turnover group ,the osteoid volume and surface,mineralization surface, corrected mineralization rate,osteoclast number, and bone formation rate were elevated (P<0.01), but mineralization lag time was reduced (P< 0' 01) in the high turnover group,and all the above parameters in the low turnover group were opposite (P <0.05 0. 01).In comparison with the 3 agegroups (51￣60, 60￣70,>70),the bone volume and osteoid volume dropped as the age increased. Both high and low turnover situations appeared in the 51￣60 age group,waied had the highest ratio in the 61￣70 age group and the lowest ratio in the >70 age group. All these changes of bone volume and turnover reflect the heterogeneity of etiology and complicacy of pathogenesis in this disease.Bone biopsy is not only to distinguish osteoPOrosis from ostcomalacla, but also to determine the turnover type and direct clinical treatment.