Biopsy Evidence Research Articles

Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management.

Multiple myeloma accounts for approximately 10% of hematologic malignancies. The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L and urine monoclonal protein is ≥200 mg/24 h), or >1 focal lesion on magnetic resonance imaging. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma. In patients who are candidates for autologous stem cell transplantation, induction therapy consists of anti-CD38 monoclonal antibody plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT). Selected standard risk patients can delay transplant until first relapse. Frail patients who not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression. Standard risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma. A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse. Chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies are additional options.

Pattern of Clinical Presentation in Patients With Lymphoma.

Introduction Lymphomas take place when cells of the lymphatic system divide and re-divide in an uncontrolled fashion, and lymphomas have been termed as a "diverse group" of cancer, playing a major role in the area of oncology. The clinical behavior and manifestations of lymphomas in the head and neck region usually lack specific characteristics that would enable attribution to a specific lymphoma entity without biopsy and histological evidence. This study aimed to determine the frequency of common clinical features among patients with lymphoma. Methods This descriptive cross-sectional study was conducted at the Department of General Medicine, Lady Reading Hospital, Peshawar, from October 28, 2021 to April 28, 2022. The inclusion criteria consisted of individuals who were recently diagnosed with lymphoma and were between the ages of 10 and 50, regardless of their gender. This study enrolled a total of 186 patients diagnosed with lymphoma and assessed for common signs and symptoms. The data-gathering process included in-depth interviews, evaluations of medical history, physical exams, and initial investigations. The data analysis was done using IBMSPSSStatistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Results The mean age of the patients was 34.5±9.6 years. Out of the total, 115 (61.8%) were men and 71 (38.2%) were women. With regard to symptoms, 134 (72%) had a fever, 80 (43%) had abdominal pain, 102 (54.8%) had vomiting, 49 (26.3%) had a headache, 111 (59.7%) had weight loss, and 17 (9.1%) had a cough. With regardto signs, 33 (17.7%) had painless lymphadenopathy, 58 (31.2%) had jaundice, 157 (84.4%) had anemia, 147 (79%) had hepatomegaly, 160 (86%) had splenomegaly, 24 (12.9%) had ascites, and 16 (8.6%) had abdominal tenderness. Conclusion The varied clinical appearance of lymphoma makes treatment difficult. In severe cases of lymphoma, early and timely diagnosis is crucial for proper and prompt treatment. The signs and symptoms, along with demographic information of patients, thorough medical history, imaging testing, andclinical examination,may indicate lymphoma.

Chinese guidelines on the management of endometrial hyperplasia

• Endometrial hyperplasia can be classified as either hyperplasia without atypia or atypical hyperplasia.• Abnormal uterine bleeding is the most common symptom of endometrial hyperplasia. Transvaginal ultrasound is recommended for initial imaging to evaluate endometrial hyperplasia (evidence level 2+), while transrectal ultrasound is recommended for virgo patients (evidence level 3).• Endometrial biopsy should be used to confirm diagnosis in patients where endometrial lesions are suspected. Effective histological approaches to make definite diagnoses include diagnostic curettage (evidence level 2++), hysteroscopic-guided biopsy (evidence level 2+) and endometrial aspiration biopsy (evidence level 2-).• Progesterone is the preferred medication for the treatment of endometrial hyperplasia without atypia. Compared to oral progestins, placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with higher regression rates, lower recurrence rates and fewer adverse events which can be the initial treatment method. (Meta evidence level 1-, RCT evidence level 2+). Ultrasound and endometrial biopsies should be performed every 6 months during treatment to evaluate its effect and treatment should continue until no pathological changes are observed in two consecutive endometrial biopsies. Hysterectomy is not the preferred choice of treatment for patients with endometrial hyperplasia without atypia.• Minimally invasive hysterectomy is indicated for patients with endometrial atypical hyperplasia (evidence level 1+), bilateral fallopian tubes should also be removed (evidence level 2+). In cases where surgery cannot be tolerated, fertility is desired or the patient is younger than 45 years old, medical therapy is recommended (evidence level 3). LNG-IUS is the preferred medical therapy method (evidence level 2+). Endometrial pathologic evaluation should be performed every 3 months during conservative treatments, with adjustments made to dosages or approaches based on observed response to medication. Treatment should continue until no pathological changes are detected in two consecutive endometrial biopsies (evidence level 2++). There is no indication of sentinel lymph nodes biopsy and/or lymphadenectomy for hyperplasia with or without atypia.• Total hysterectomy is recommended to treat patients with recurrent endometrial atypical hyperplasia (evidence level 3); however, medical conservative therapy may be considered for patients hoping to become pregnant in the future.• Patients with fully regressed disease who would like to become pregnant should be advised to seek assistance through assisted reproductive technologies (evidence level 3).• Long-term follow-up is suggested for patients after endometrial hyperplasia treatment (evidence level 2+). Patient education is imperative for improving medication adherence, increasing regression rates and lowering recurrence rates (evidence level 3).

A291 ANA-NEGATIVE AUTOIMMUNE HEPATITIS IN A 30-YEAR-OLD FEMALE: A DIAGNOSTIC CHALLENGE

Abstract Background Autoimmune Hepatitis (AIH) is a chronic liver condition arising from the immune system's attack on liver cells. Its diagnosis is typically supported by the presence of autoantibodies, notably ANA. However, cases have been identified where AIH occurs in the absence of these conventional serologic markers. Prior studies have reported that ANA-negative AIH patients showed more acute presentations and higher frequencies of histologic acute hepatitis compared to those with positive autoimmune serology. As such, ANA-negative subset of patients presents a diagnostic challenge but highlights the evolving understanding of autoimmune processes in liver diseases. Aims To detail the clinical presentation, investigative measures, and treatment approach in a an otherwise healthy 30-year-old female diagnosed with ANA-negative autoimmune hepatitis. Methods The diagnostic approach included clinical symptomatology, biochemical tests, imaging via abdominal ultrasound, and histopathological evidence from an ultrasound-guided liver biopsy Results The patient presented initially with epigastric pain, jaundice, and pruritus over two weeks. Blood tests revealed acute hepatitis: ALT at 2723 U/L[JA1] , AST at 1428 U/L, and hyperbilirubinemia at 503 μmol/L, with GGT and ALP remaining normal. An abdominal ultrasound presented a typical liver morphology and biliary system. Initial autoimmune liver disease panels, including ANA, and viral hepatitis screenings, returned negative results. Furthermore, the patient's medication and drug history provided no additional clues for drug-induced aetiologies. For more conclusive diagnostics, an US-guided liver biopsy was performed during the admission revealing moderate acute hepatitis characterized by both interface hepatitis and lobular inflammation, prompting the suspicion for ANA-negative AIH. Initiating prednisone treatment (40 mg daily) based on clinical and biopsy evidence led to a significant reduction in liver enzymes and bilirubin. By the time of her discharge, her primary residual symptoms were mildly controlled jaundice and pruritus. She was transitioned to a tapering dose of prednisone, and Azathioprine was later added to her regimen. Subsequent close follow up revealed complete resolution of her symptoms. Notably, a 7-month follow-up unveiled a previously undetected AIH marker: ASMA with a titre of 1:80. Conclusions ANA-negative AIH, as showcased in this case, emphasizes the importance of a thorough and iterative diagnostic approach. Traditional serological markers may not always be present, necessitating reliance on a combination of clinical presentations and histopathology. Regular follow-ups and periodic re-evaluations are essential. This approach is crucial for pinpointing the diagnosis, guiding effective therapeutic interventions, and ultimately ensuring positive outcomes for patients navigating complex autoimmune liver conditions. Funding Agencies None

Sensory Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Neglected Immunotherapy-Responsive Sensory Neuropathy.

To report an improvement with immunotherapy in 34 (85%)/40 patients who required an immunotherapy among 56 patients with sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired, chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy that had progressed for >2 months; and 2) definite electrophysiological and/or biopsy evidence of demyelinating neuropathy. Fifty-six patients with sensory CIDP were identified. Evidence of demyelination was obtained from by the routine motor nerve conduction study (NCS) in 39 (70%) patients, from a nerve biopsy in 10, and from a near-nerve needle sensory NCS in 7 patients. The most prominent laboratory abnormality was a high protein level in the cerebrospinal fluid in 21 (49%) of 43 tested patients. Immunotherapy was required in 41 (79%) of the 52 followed-up patients. An improvement with immunotherapy was observed in 36 (88%)/41 patients. In three patients, motor weakness developed in 5-8 years' follow-up period and so, their diagnosis was changed to CIDP. Sensory CIDP is responded to an immunotherapy in 88% of the treated patients. Sensory CIDP was diagnosed by the routine motor NCS in 70% of patients and by a sural nerve biopsy in 18% of patients. Thus, sensory CIDP should be recognized as a treatable CIDP variant among the different types of "idiopathic sensory neuropathy."

Systemic AL Amyloidosis in Patients Younger Than 40 Years of Age: Clinical Presentation and Outcomes

Background: The median age at diagnosis for systemic AL amyloidosis is reported to be 64 years. A small number of patients are diagnosed at a much younger age, i.e., before 40 years. The characteristics and prognosis of these patients are not well known, and perhaps they require unique considerations due to the earlier onset of disease. A closer understanding of this patient population could help guide management approach and improve long term outcomes. Aim: In this study, we aimed to describe the presenting clinical features, hematologic profiles and outcomes of young patients with AL amyloidosis. Methods: Patients with systemic AL amyloidosis and age ≤ 40 years at diagnosis who presented to the Boston University Amyloidosis Center between 2000 and 2023 were identified from our prospectively maintained database of consented patients (ClinicalTrials.gov Identifier: NCT00898235). All patients had clinicopathological evidence of systemic AL amyloidosis, with positive Congo red staining of a biopsy specimen and evidence of a plasma cell dyscrasia. We collected clinical data both from the database and medical records of these patients. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and hazard ratios (HR) computed from multivariable Cox proportional hazard models for OS. Results: Of 1,722 patients with AL amyloidosis evaluated during the study period, we identified 45 (2.6%) patients who were diagnosed at ≤ 40 years of age. The median age was 37 years (range 21-40) and only 4 patients were ≤ 30 years of age. Presenting characteristics are shown in Table 1. Notably, this cohort had a median B-type natriuretic peptide of 87 pg/mL (range 0-2,346), troponin-I of 0.012 ng/mL (range 0-3.192), interventricular septum of 11 mm (range 5-18), and 6-minute walking distance (6MWD) of 396 meters (range 183-731). The median time from symptom onset to diagnosis was 8 months (range 1-72). The majority (n = 32, 71%) were treated with high-dose melphalan and stem cell transplantation (HDM/SCT) as frontline therapy. Meanwhile, 11 patients received non-SCT treatments, including melphalan/dexamethasone (7%), daratumumab-CyBorD (4%), CyBorD (2%), bortezomib/dexamethasone (2%), and dexamethasone alone (2%). Of the evaluable patients (n = 31), 39% achieved hematologic complete response to any regimen at 6-12 months following treatment. With a medianfollow-up of surviving patients of 9.0 years, the median OS was 16.7 years (95% CI 11.6-16.9). Of the cohort, a total of 20 patients (44%) died. Patients treated with HDM/SCT had median OS of 16.9 years; meanwhile, those treated with non-SCT therapies had a median OS of 1.3 years. On multivariate analysis, time from symptom onset to diagnosis of >6 months (HR 2.21, p = 0.21) and 6MWD < 400 meters (HR 1.37, p = 0.66) were independently associated with increased risk of mortality. Conclusions: Young patients with AL amyloidosis who are diagnosed before 40 years of age have a prolonged survival if treated with intensive treatment with HDM/SCT if eligible. Longer time to diagnosis from symptom onset and 6-minute walk distance are important prognostic factors in this patient population.

Association of Implantation Biopsy Findings in Living Donor Kidneys With Donor and Recipient Outcomes

Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes. Retrospective cohort study. Single center, living donor kidney transplants from January 2010 to July2022. Chronic histological changes, glomerular disease in donor kidney implantation biopsies. For donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss,≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m2 at 6 months after donation; for recipients, death-censored allograft survival. Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes. Among 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m2. There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities. Retrospective, absence of measured GFR. Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival. Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients.

Testing and Management of Iron Overload After Genetic Screening–Identified Hemochromatosis

HFE gene-associated hereditary hemochromatosis type 1 (HH1) is underdiagnosed, resulting in missed opportunities for preventing morbidity and mortality. To assess whether screening for p.Cys282Tyr homozygosity is associated with recognition and management of asymptomatic iron overload. This cross-sectional study obtained data from the Geisinger MyCode Community Health Initiative, a biobank of biological samples and linked electronic health record data from a rural, integrated health care system. Participants included those who received a p.Cys282Tyr homozygous result via genomic screening (MyCode identified), had previously diagnosed HH1 (clinically identified), and those negative for p.Cys282Tyr homozygosity between 2017 and 2018. Data were analyzed from April 2020 to August 2023. Disclosure of a p.Cys282Tyr homozygous result. Postdisclosure management and HFE-associated phenotypes in MyCode-identified participants were analyzed. Rates of HFE-associated phenotypes in MyCode-identified participants were compared with those of clinically identified participants. Relevant laboratory values and rates of laboratory iron overload among participants negative for p.Cys282Tyr homozygosity were compared with those of MyCode-identified participants. A total of 86 601 participants had available exome sequences at the time of analysis, of whom 52 994 (61.4%) were assigned female at birth, and the median (IQR) age was 62.0 (47.0-73.0) years. HFE p.Cys282Tyr homozygosity was disclosed to 201 participants, of whom 57 (28.4%) had a prior clinical HH1 diagnosis, leaving 144 participants who learned of their status through screening. There were 86 300 individuals negative for p.Cys282Tyr homozygosity. After result disclosure, among MyCode-identified participants, 99 (68.8%) had a recommended laboratory test and 36 (69.2%) with laboratory or liver biopsy evidence of iron overload began phlebotomy or chelation. Fifty-three (36.8%) had iron overload; rates of laboratory iron overload were higher in MyCode-identified participants than participants negative for p.Cys282Tyr homozygosity (females: 34.1% vs 2.1%, P < .001; males: 39.0% vs 2.9%, P < .001). Iron overload (females: 34.1% vs 79.3%, P < .001; males: 40.7% vs 67.9%, P = .02) and some liver-associated phenotypes were observed at lower frequencies in MyCode-identified participants compared with clinically identified individuals. Results of this cross-sectional study showed the ability of genomic screening to identify undiagnosed iron overload and encourage relevant management, suggesting the potential benefit of population screening for HFE p.Cys282Tyr homozygosity. Further studies are needed to examine the implications of genomic screening for health outcomes and cost-effectiveness.

Imaging spectrum in rhino-orbito-cerebral mucormycosis: a cross-sectional study.

Rhino-orbital-cerebral mucormycosis (ROCM) is a life-threatening condition caused by a saprophytic fungus that predominately affecting immune-compromised patients. Early diagnosis of ROCM is of utmost importance to start the treatment as early as possible to prevent early and horrible complications of the disease. This retrospective study evaluated the imaging findings of 21 patients with biopsy and KOH mount-based evidence of invasive ROCM. The imaging was obtained from a Siemens Magnetom Amira 1.5T system with a strength of 1.5T or more. The spectrum of findings was evaluated for the sites of involvement, signal intensity, contrast characteristics, necrotic component as well as orbital, infratemporal, and intracranial extensions, especially cavernous sinuses, Meckel's cave, and the brain parenchyma. The mean age of the patients was 55.8±10.9 years and included 71% male. All the patients were positive for COVID-19 and the majority were diabetic. MRI showed predominant involvement of the maxillary sinus (17, 81%) and the ethmoidal sinus (15, 71.4%). The orbital extension was present in 18 cases (86%). T1-weighted imaging showed iso to low signal intensity in involved sinuses in the majority of the patients (9, 42.9%). Heterogeneously high signal intensity was observed in T2-weighted and short tau inversion recovery images in all the patients. Heterogenous contrast enhancement was present in 20 (95.2%) patients. The imaging spectrum of ROCM is variable. Multiplanar MRI with postcontrast images is a very useful complementary tool to the clinical evaluation to assess the extent of disease and its complications, which has a high mortality. Clinicians and radiologists should be aware of the imaging spectrums of ROCM.

Validation of an ICD-10 case-finding algorithm for endometrial cancer in US insurance claims.

To evaluate the positive predictive value (PPV) of an endometrial cancer case finding algorithm using International Classification of Disease 10th revision Clinical Modification (ICD-10-CM) diagnosis codes from US insurance claims for implementation in a planned post-marketing safety study. Two algorithm variants were evaluated. Provisional incident endometrial cancer cases were identified from 2016 through 2020 among women aged ≥50 years. One algorithm variant used diagnosis codes for malignant neoplasms of uterine sites (C54.x), excluding C54.2 (malignant neoplasm of myometrium); the other used only C54.1 (malignant neoplasm of endometrium). A random sample of medical records of recent incident provisional cases (2018-2020) was requested for adjudication. Confirmed cases showed biopsy evidence of endometrial cancer, documentation of cancer staging, or hysterectomy following diagnosis. We estimated the PPV of the variants with 95% confidence intervals (CI) excluding cases that had insufficient information. Of 294 provisional cases adjudicated, 85% were from outpatient settings (n = 249). Mean age at diagnosis was 69.3 years. Among the 294 adjudicated cases (identified with the broader algorithm variant), the same 223 were confirmed endometrial cancer cases by both algorithm variants. The PPV (95% CI) for the broader algorithm variant was 84.2% (79.2% and 88.3%), and for the variant using only C54.1 was 85.8% (80.9% and 89.8%). We developed and validated an algorithm using ICD-10-CM diagnosis codes to identify endometrial cancer cases in health insurance claims with a sufficiently high PPV to use in a planned post-marketing safety study.

Analytical correlation of Laboratory tests with clinical findings in cases of Paraproteinemia

Multiple myeloma is a malignant plasma cell disorder identified with M spikeon serum protein electrophoresis (SPE) during routine laboratory work up. This study aimed to analyze the utility of laboratory tests suchas SPE, immunofixation electrophoresis (IFE), CBC, RFT, LFT, calcium, phosphorus, beta 2 microglobulins, LDH, serum-free light chain assay (SFLC), Bence Jones Proteinuria (BJP), BM biopsy, BM smear and radiological evidence for lytic lesionsin cases of paraproteinemia. Data for the above parameters from 2017 January to 2021 March were obtained from the data management system of the central lab. Biochemical parameters were correlated with M spike value using Karl Pearson’s correlation coefficient (P-value &lt;0.05 will be significant).7.7% SPE reports had M spike with a mean age of 64 years in males and 63 years in females (male/female ratio, 1: 0.76). M spike showed a significant positive association with total protein, globulin, uric acid and negative association with albumin. IgG kappa type (51%) predominant in IFE reports. The common presentation from hematological data was normocytic normochromic anemia with occasional rouleaux formation. Osteolytic lesion was present in 86% of reported cases. Associated biochemical, hematological, and radiological correlates of the positive cases could be documented in only less than 20% of the positive cases. Ours is a tertiary care hospital and the associated lab is also a reference lab where samples from in and around the city are tested. After the preliminary SPE, it could be possible that the patients were further evaluated and continued treatment at some other facility.

RWD122 The Application of Artificial Intelligence for Enhanced Diagnosis of Prostate Cancer Using Biopsy Evidence That Are Substantiated By Genetic Markers

Although the most prevalent approach for the detection and diagnosis of prostate cancer is by examining the biopsy images, the presence of substantial variability in biopsy analysis often leads to delays in optimized treatment. The recent advancements in the genomic domain, with coding and non-coding genes as biomarkers along with sequencing data using artificial intelligence (AI), have led to improved decision making and better clinical management. In this study, we propose a hybrid approach that combines the state-of-the-art technologies for image processing and genomic features for an effective detection of Gleason score in the field of prostate carcinogenesis.

Clinicopathological features and treatment profile of patients referred to a sarcoma medical oncology centre in India: Challenges and insights from the developing world.

e23533 Background: Sarcomas are rare cancers that warrant expert pathologic diagnosis (dx) and multidisciplinary treatment (MDT). We analysed details of patients (pts) diagnosed with soft tissue sarcomas (STS) and bone sarcomas (BS) referred to our centre. Methods: This is a retrospective study of pts diagnosed with STS or BS referred to All India Institute of Medical Sciences, Delhi between January 2021 and December 2022. Histopathological discrepancies were noted as change of primary dx or differences in grading or sarcoma subtyping on pathology review. Surgical and/or medical deviations from standard practise were identified. SPSS 26.0 was used for statistical analysis. Results: 268 pts with median age of 35 years (range 8 months-85 years) and male predominance (n = 140, 52.2%) were included. 121 (45%) pts belonged to adolescent and young age (AYA) group. 163 (61%) pts came from urban/semi-urban background and from a median distance of 90 miles (range 6.2-1587). Median symptom duration prior to referral was 9 months (range 6 months-12 years). Based on biopsy or cytopathological evidence, referred pts included 186 (69.4%) with STS, 73 (27.2%) with BS, 7 with undifferentiated sarcoma (2.6%) and 2 with carcinoma (0.7%). The most common STS (n = 186) were leiomyosarcoma (14%), synovial sarcoma (12%) and liposarcoma (8.3%); BS (n = 73) included osteosarcoma (44%), Ewing sarcoma (44%), chondrosarcoma (9.5%). Molecular and/or germline mutation tests were performed only in 9 of 131 (6.8%) indicated cases before referral. Localized/locally advanced and metastatic stages were found in 94 (35.6%) and 116 (43.2%) resp; rest (21.2%) did not undergo staging work-up outside. Common primary sites were extremity (n = 127, 44.4%), abdomen (n = 71, 24.8%), thorax (n = 24, 8.3%). 125 (43.7%) and 91 (31.8%) pts had undergone surgery and chemotherapy resp outside. 1st line chemotherapy (n = 85) was anthracycline-based (n = 65, 76.4%), ifosfamide-based (n = 6, 7%), gemcitabine-docetaxel (n = 5, 5.8%). 2nd line (n = 29) was gemcitabine +/- docetaxel (n = 7, 24.1%), anthracycline (n = 6, 20.6%), ifosfamide-based (n = 6, 20.6%), pazopanib (n = 6, 20.6%). Pathologic discrepancies found in 87 (30.4%) pts included change of primary diagnosis in 44 (15%), sarcoma subtype variation in 35 (12.2%) and benign disorder misclassified as malignancy in 5 (1.7%) pts. Deviations in chemotherapy (n = 43, 47.2%) included inadequate dose/cycles in 18 (42%), no chemotherapy despite indication in 8 (18.6%), non-standard regimens in 10 (23%) pts. Distance/rural residence did not correlate with pathology/treatment deviations. Conclusions: In this era of precision medicine and targeted oncology, our findings reflect the need for well-equipped diagnostic and treatment facilities. The lack of expert centres catering to pts with sarcomas remains a challenge in developing countries.

MP06-11 IMPLEMENTATION OF A PAY-FOR-PERFORMANCE MODEL TO ENHANCE THE UPTAKE OF CONSERVATIVE MANAGEMENT FOR LOW-RISK PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP06-11 IMPLEMENTATION OF A PAY-FOR-PERFORMANCE MODEL TO ENHANCE THE UPTAKE OF CONSERVATIVE MANAGEMENT FOR LOW-RISK PROSTATE CANCER Franklin Gaylis, Paul Dato, William Catalona, Matthew Cooperberg, Rose Prime, Julie Cramer, David Prock, Katayune Golshan, Sonia Romo, Steven Hu, and Edward Cohen Franklin GaylisFranklin Gaylis More articles by this author , Paul DatoPaul Dato More articles by this author , William CatalonaWilliam Catalona More articles by this author , Matthew CooperbergMatthew Cooperberg More articles by this author , Rose PrimeRose Prime More articles by this author , Julie CramerJulie Cramer More articles by this author , David ProckDavid Prock More articles by this author , Katayune GolshanKatayune Golshan More articles by this author , Sonia RomoSonia Romo More articles by this author , Steven HuSteven Hu More articles by this author , and Edward CohenEdward Cohen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003217.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Genesis Healthcare Partners (GHP), a large urology group in Southern California, together with the Prostate Cancer Active Surveillance Project (PCASP) and UnitedHealthcare (UHC) developed a Pay-for-Performance (P4P) demonstration project to enhance the uptake of conservative management (active surveillance [AS], watchful waiting [WW]) for men with low-risk prostate cancer (LRPCa) and leverage the Electronic Medical Record (EMR) to obtain granular, high fidelity data. METHODS: Four evidence-based quality measures and their respective thresholds were developed: 1. completion of an EMR embedded template documenting both risk and management (90% threshold), 2. adoption of AS/WW for LRPCa (75% threshold), 3. 2 PSA tests/year for AS (75% threshold), 4. confirmatory biopsy within 18 months of the diagnostic biopsy (75% threshold). Structured templates were embedded into the Allscripts EMR. Data were electronically queried from the structured templates using Microsoft Access and analyzed and reported in Microsoft Excel. Biannual PSA data and evidence of a confirmatory biopsy will be reported on an annual basis. Data are presented from inception of the project on January 1st, 2022 through September 30th, 2022. RESULTS: For the first three quarters of the study, January through September 2022, there was a progressive increasing trend in template completion; Q1 71/107 (67%), Q2 97/137 (73%), Q3 67/80 (86%). Table 1 includes PCa risk levels and management selection for men with newly diagnosed PCa during the period of study. CONCLUSIONS: This P4P project is a novel approach to enhancing the uptake of AS for men with LRPCa. Implementation of the P4P intervention via EMR embedded templates demonstrates the potential to leverage the EMR and obtain granular data including patient risk stratification and management selection. Early results indicate excellent physician participation and improved AS uptake (76%) for patients with LRPCa compared to national trends. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e57 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Franklin Gaylis More articles by this author Paul Dato More articles by this author William Catalona More articles by this author Matthew Cooperberg More articles by this author Rose Prime More articles by this author Julie Cramer More articles by this author David Prock More articles by this author Katayune Golshan More articles by this author Sonia Romo More articles by this author Steven Hu More articles by this author Edward Cohen More articles by this author Expand All Advertisement PDF downloadLoading ...

Head and Neck Lymphomas in Jos University Teaching Hospital Nigeria: A Five Year Review

<i>Introduction</i>: Lymphomas are heterogeneous group of lymphoid tissues traditionally categorized as either Hodgkin’s Lymphoma (HL) or Non-Hodgkin’s Lymphoma (NHL). The head and neck region is rich in lymphoid tissues, thus a fertile anatomic site for the development of lymphoid proliferative diseases like lymphomas. In the head and neck, malignant lymphomas account for 5% of all malignant neoplasm; Non-Hodgkin’s Lymphoma (NHL) is the most common accounting for 75%. The clinical behaviour and manifestations of Lymphomas in the head and neck lack specific characteristics that would enable attribution to a specific lymphoma entity without biopsy and histological evidence. <i>Materials and Methods</i>: It is a 5 year retrospective study of confirmed histopathological analysis of head and neck lymphomas from 1^st January 2017 to31^st December 2021. Case notes of all histopathologically confirmed head and neck lymphomas were retrieved from the medical records department and also theatre records as supportive data were analysed for age, sex, histological diagnosis, tumour site, duration of symptoms before presentation and treatment modality; and then discussed. <i>Results</i>:-The total number of patients seen during the period under review was 1678, 16 patients had histopathologically confirmed lymphomas out of 388 patients with head and neck tumours, thus prevalence of 0.1% and 4.1% of all head and neck tumours. Male to Female ratio of 5:1, age range of 4 to 62 years, mean age of 29 years. Most common tumour site is the cervical region-315; the most frequently seen histological type is the Non Hodgkin’s lymphoma (NHL) and the most common duration of symptom before presentation is over 1 year-50%. All patients had chemotherapy as a treatment modality. <i>Conclusion</i>: This study reveals the management challenges of the head and neck lymphomas are due to late presentation, financial constraints and ignorance. Health awareness and adequate Health Insurance Policy are needed to cope or mitigate these problems.

Data-independent acquisition mass spectrometry reveals comprehensive plasma protein profiles in the natural history of patients with hereditary transthyretin amyloidosis (ATTRv)

ABSTRACT Objectives Hereditary transthyretin amyloidosis (ATTRv) is a rare, fatal, autosomal dominant disease with more than 140 mutations discovered. Three phenotypes of amyloid infiltration are neuropathy (ATTRv-PN), cardiopathy (ATTRv-CM), and neuropathy + cardiopathy (ATTRv-MIX). The lack of ATTR-specific biomarkers, difficulties in biopsy evidence, and limited known pathogenic mechanisms have made diagnosis difficult. Newly emerging noninvasive measures for monitoring progression and disease-modifying therapies have improved early diagnosis and patient management. Methods Our research applies the latest technology, Data-Independent Acquisition-Based Quantitative Proteomics (DIA), to reveal comprehensive plasma protein profiles in the natural history of Chinese patients with hereditary transthyretin amyloidosis (ATTRv). We analyzed differentially expressed proteins (DEPs) in three phenotypes (ATTRv-PN, ATTRv-CM, and ATTRv-MIX). Results Serum samples were collected from a total of 18 patients (6 ATTRv-PN, 5 ATTRv-CM, and 7 ATTRv-MIX patients) and 20 healthy participants as a control group. Combined with the results of the proteomic and bioinformatic analyses, we found 30 DEPs and protein interaction networks clustered in KRT family proteins and DSC3 between ATTRv-PN and the control, which were rich in the estrogen signaling pathway and the cell adhesion molecule (CAM) pathway. Conclusion This study demonstrates a global and significant proteomic profile in different stages of ATTRv.

Endobronchial ultrasound: Indispensable or Dispensable- Our experience through Case Series

Abstract EBUS has been an important interventional Pulmonology (IP) tool in respiratory medicine practice. We enlist our observations after including EBUS in our services. A total of 35 cases referred for EBUS were assessed. Of these, 33 underwent linear EBUS and 2 VBN. EBUS could be done in 21/33 (63.6%) cases. In 12/33 (36.4%), EBUS was not done as it was unindicated or due to contraindications. Of the 21 cases wherein EBUS was performed, FNA/FNB could be done in 17 (81%) but could not be done on 4 (19%). Of these 17 cases, FNA/FNB was conclusive in 9 (53%), inconclusive with alternate site biopsy yielding diagnosis in 6 (35%), and inconclusive with no other biopsy evidence in 2(12%). The final etiology in the 35 cases was TB, malignancy, sarcoidosis, and others in 19 (54%), 9(26%), 3 (9%), and 4 (11%) cases, respectively. Of the 12/19 cases of TB wherein EBUS FNA/FNB was feasible, 8 were diagnostic (all cases of IMHL), 3 yielded diagnosis on other EP site biopsies, and in one case, no biopsy could be done. EBUS, while optional, proves indispensable in situations like IMHL (Isolated Mediastinal and Hilar Lymphadenopathy). The utility of TB was important to achieving biopsy evidence.

The Role of NOTCH1, GATA3, and c-MYC in T Cell Non-Hodgkin Lymphomas.

Simple SummaryPeripheral T cell lymphomas (PTCLs) comprise 10–15% of all non-Hodgkin lymphomas, and are more aggressive with worse prognosis. Due to their rarity and significant molecular abnormalities, the pathogenesis of PTCLs is not well understood. The expressions of NOTCH1, GATA3, and c-MYC have been linked to a poorer prognosis in PTCL, and are implicated in downstream processes. The aims of this review are to elucidate the role of NOTCH1, GATA3, and c-MYC in patients with PTCLs to provide additional information about the disease’s pathogenesis and to investigate the master regulator between these genes that will provide a basis for new therapeutic strategies and improve PTCL patients’ survival rates. NOTCH1 greatly influences the progression, pathogenicity, and development of PTCLs. Because NOTCH signalling does not rely on enzymatic signal amplification, and all Notch ligands and receptors include extracellular domains that are essential for receptor binding and activation, making them accessible to circulating therapies and targeting for different therapeutic strategies.Lymphomas are heterogeneous malignant tumours of white blood cells characterised by the aberrant proliferation of mature lymphoid cells or their precursors. Lymphomas are classified into main types depending on the histopathologic evidence of biopsy taken from an enlarged lymph node, progress stages, treatment strategies, and outcomes: Hodgkin and non-Hodgkin lymphoma (NHL). Moreover, lymphomas can be further divided into subtypes depending on the cell origin, and immunophenotypic and genetic aberrations. Many factors play vital roles in the progression, pathogenicity, incidence, and mortality rate of lymphomas. Among NHLs, peripheral T cell lymphomas (PTCLs) are rare lymphoid malignancies, that have various cellular morphology and genetic mutations. The clinical presentations are usually observed at the advanced stage of the disease. Many recent studies have reported that the expressions of NOTCH1, GATA3, and c-MYC are associated with poorer prognosis in PTCL and are involved in downstream activities. However, questions have been raised about the pathological relationship between these factors in PTCLs. Therefore, in this review, we investigate the role and relationship of the NOTCH1 pathway, transcriptional factor GATA3 and proto-oncogene c-MYC in normal T cell development and malignant PTCL subtypes.

Machine learning application to find patients with lower-risk myelodysplastic syndrome from real-world data.

1555 Background: It is a challenge to identify patients with myelodysplastic syndrome (MDS) using structured data from electronic health records (EHRs). Current claims-based algorithms incorporating diagnosis codes, clinical labs, and procedures have not been validated against an expert reference standard. A machine learning-based approach was investigated to identify erythropoietin-stimulating agent (ESA)-treated, lower-risk (LR)-MDS patients from structured EHR data. Methods: A sample of 1,549 patients from the Syapse Learning Health Network (SLHN) was identified as potential ESA-treated LR-MDS patients by a team of clinicians and epidemiologists based on diagnosis and medication data from multiple health systems’ EHRs and cancer registries. Of these, 404 (25%) were confirmed as ESA-treated LR-MDS patients through a review of patient records by certified cancer registrars (CTRs). The sample was divided into training and validation sets at a ratio of 80/20, stratified by the outcome. Age, sex, diagnosis codes corresponding to MDS and chronic kidney disease, medication (ESA, luspatercept, lenalidomide), clinical lab tests (hemoglobin, absolute neutrophils, platelet, blast percentage), and evidence of bone marrow biopsy were included as the predictive variables for the models. Gradient boosting machines with a nested cross-validation scheme were adopted to build the optimal model on the training set. Model acceptance was evaluated based on precision and recall on the validation set. The optimal model was then applied to the remaining unscreened SLHN patient population. Results: The optimal model identified an additional cohort of 157 patients based on the predicted likelihood. Among these, 69 (44%) were CTR-confirmed ESA-treated LR-MDS patients, all of whom were previously missed by the initial expert-determined selection criteria, as shown in the table. Conclusions: The application of machine learning methods increased the rate of ESA-treated MDS patient identification even after the expertly-determined population was depleted. This suggests the application of machine learning models using EHR data may improve the efficiency of MDS patient identification and screening efforts for research, quality improvement, and clinical care. [Table: see text]

Metagenomic identification of gut microbiota distribution on the colonic mucosal biopsy samples in patients with non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is known to be the most common liver disease in the world, and there are currently no approved pharmacological treatments to prevent or treat this condition. In addition to being associated with an increased risk of hepatocellular carcinoma and cirrhosis, NAFLD has now become the leading cause of liver failure-associated transplantation. The 16S rRNA gene which conserved regions can serve as universal primer binding sites for PCR amplification of gene fragments, while hypervariable regions contain significant sequence diversity useful for prokaryotic identification purposes. 16S rRNA gene sequences can be use by researchers to identify prokaryotic taxonomy found in clinical samples. As a result of increasing microbiota studies with developing technological developments, the role of intestinal microbiota in the pathogenesis of NAFLD is revealed in an important way. In this study, it was aimed to determine the clinical prognostic importance of gut microbiota in the pathogenesis of NAFLD and to determine the microbial composition with intestinal mucosal biopsy samples in NAFLD patients. Material and methodWe included 20 patients diagnosed with NAFLD as a result of liver function tests, histological, ultrasonographic, biopsy evidence and 20 normal control groups created under exclusion criteria in this study. The healthy control group of the same age and gender as the patients were determined to be equal, and the age, gender, BMI, insulin resistance, AST, ALT levels of the individuals were recorded for analysis. İntestinal mucosal biopsy samples were taken from the individuals included in the study under sterile conditions. Microbial results were obtained as a result of 16S rRNA amplicon metagenomic processes. The region of approximately 1500 bp covering the V1-V9 region of the 16S rRNA gene was targeted to detect microbial diversity. The amplified regions were sequenced using next-generation sequencing. Operational Taxonomic Unit (OTU) value was obtained with bioinformatics software with the obtained sequence data. The analysis of the recorded parameters was done with the SPSS.19 statistical program. ResultsIn the designed study, 16 phyla, 28 class, 56 order, 128 family, 415 genera, 1041 species microorganisms were analyzed taxonomically in a total of 40 individuals. In our study, Intestinal microbial diversity is lower in NAFLD patients compared to control group individuals. In addition, gram-negative bacteria were found to be more dominant in NAFLD patients. As a phylum, Proteobacteria increased in NAFLD group, Bacteroidetes and Actinobacteria in control group, while Firmicutes had equal distribution in both groups. BMI OR = 6.37, 95 %CI (0.39–0.40) p value was 0.001 in laboratory data, whereas Proteobacteria OR = 1.754, 95% CI (0.901–3.416), p value 0.05 in microbial profile. ConclusionThe 16S rRNA metagenomic study of intestinal microbiota using colonic mucosal biopsy samples in NAFLD disease was the first study in the Turkish population, and important data were obtained for other studies. In the data obtained, we think Proteobacteria, Ruminococcaceae, Escherichia coli and Bacilli are very important in both diagnostic and treatment options as a microbial profile in NAFLD.