14 research outputs found
Systemic Sclerosis with Gastrointestinal manifestations: a unique presentation
Systemic sclerosis is a chronic autoimmune disease of unknown etiology. Disease course usually begins with Raynaud’s phenomenon followed by skin sclerosis and internal organ involvement. Diagnosis is made based on the clinical symptoms, presence of antibodies and endoscopy with biopsy. With this background, we present a case of a 60-year female who was followed by GI clinic for treatment resistant dyspepsia, bloating and nausea. Past medical history was significant for fibromyalgia, Raynaud’s disease and transient ischemic attack. For evaluation of dyspepsia, she underwent endoscopy with gastric and esophageal biopsies, which were superficial and showed only non-specific chronic inflammation. Further, 24 hour pH monitoring results were unhelpful in making a definitive diagnosis. Esophageal manometry showed a hypertensive lower esophageal sphincter for which she underwent Heller’s myotomy. Her symptoms, however, persisted and she was scheduled to undergo laparoscopy and open gastric wall biopsy. Stomach biopsy revealed gastric mucosa showing focal vascular ectasia. There was significantly increased fibrosis involving the muscularis mucosae and propria (Figure A), highlighted by trichrome stain (Figure B-D). Following biopsy results, Scl-70 Ab test was performed and it turned out to be positive (42, Nunits). Thus, supporting the diagnosis of systemic sclerosis. Full thickness gastrointestinal tract biopsies of systemic sclerosis cases are rarely seen in routine surgical pathology practice. This case is unique because of the complexity of clinical presentation requiring open gastric wall biopsy but demonstrates the value of pathologic evaluation for diagnosis of rare autoimmune disorders such as systemic sclerosis.https://scholarlycommons.henryford.com/merf2020caserpt/1013/thumbnail.jp
Development of Hepatocellular Carcinoma after Achieving Sustained HCVVirologic Response and Regression of Cirrhosis
Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer mortality. Interferon/ribavirin and direct acting antiviral (DAA) therapy have successfully treated HCV infection and may halt the progression of fibrosis. It is generally believed that HCC primarily occurs in the background of HCV- related cirrhosis; theoretically, achieving sustained viral response (SVR) could decrease the incidence of HCC by slowing down fibrosing process; hence preventing progression of cirrhosis. Here, we present a case of 64-year-old female who was successfully treated for HCV infection with interferon in 1994. Patient achieved sustained viral response (SVR) and has been in remission for 23 years. In June 2017, she presented with abdominal pain and CT scan revealed a liver mass which was subsequently biopsied and proved to be HCC. Patient was treated with partial hepatectomy and histologic examination of the resected liver mass revealed well-differentiated HCC; non-neoplastic liver demonstrated features of regression of cirrhosis/fibrosis with fibrous expansion of few portal tracts and scattered very fine curvilinear fibrous septa; no portal/lobular inflammation was present. The patient developed HCC 23 years after achieving SVR. Significant regression of cirrhosis/fibrosis in the non-neoplastic liver argues against the usual course of HCC development in cirrhotic/advanced fibrotic setting, and suggests the possibility of an alternative phenomenon, e.g., latency of HCV and/or oncologic potential of HCV at the genomic level. This rare event raises certain questions which have not been properly investigated in the course of HCC development, such as: 1) Relationship between regression of cirrhosis/fibrosis and developing HCC; 2) If absence and regression of cirrhosis/fibrosis carries the same value; 3) Necessity of updating the surveillance criteria in patient with SVR lacking cirrhosis; and 4) Oncologic potential of HCV acquired at the genomic level; these questions/issues are currently under investigation.https://scholarlycommons.henryford.com/merf2020caserpt/1084/thumbnail.jp
Clinico-Laboratory Profile and Outcome of COVID-19 in Patients with Chronic Immune Thrombocytopenia
Background/Case Studies: Thrombocytopenia is a well-described complication of COVID-19, with numerous proposed mechanisms among which is immune thrombocytopenia (ITP). There are limited data on the characteristics and impact of COVID-19 on patients with previously diagnosed ITP.
Study Design/Methods: This is a retrospective review of all chronic ITP patients who were diagnosed with COVID-19 between 03/2020 and 01/2022 at a tertiary care center. The study was approved by the IRB. Patients with secondary thrombocytopenia, missing data, and unavailable follow up after COVID-19 diagnosis, were excluded. Demographic data, comorbidities, clinico-laboratory findings before and after COVID-19 diagnosis, management of COVID-19 and outcome were collected. Analyses were performed using SPSS; a p value of \u3c0.05 was considered significant. Results were presented as median plus range, mean +/- standard deviation, or percentages as indicated. Variables were compared using the independent two-sample Student t-test for continuous variables, and the Pearson\u27s Chi-square test or Fisher\u27s exact test for categorical variables. Early mortality was defined as death from any cause within 30 days of admission.
Results/Findings: 45 patients were included. The median age was 66 (32–93) years; 27 (60%) were females. 28(62%) patients were Caucasian. The median time from ITP diagnosis to COVID-19 was 5 (1–35) years. A 27 (60%) patients required treatment for ITP before COVID-19, and only 4 patients were on low-dose prednisone at the time of COVID-19 diagnosis. The most common symptoms of COVID-19 were shortness of breath (53%), fever (31%), and cough (22%). 29 (64%) patients were hospitalized with 12 of them requiring ICU care. Median time of hospitalization was 8 (2–45) days. COVID-19 specific treatments included steroids (42%), remdesivir (24%), chloroquine (9%), azithromycin (9%), and tocilizumab (2%). Three patients had thrombosis (2 DVTs, and 1 DVT and PE), 2 had intracranial bleeding, and 3 had mucosal bleeding. Early mortality rate was 15.6%; death was attributed to respiratory failure in 3 patients, multi-organ failure in 3 patients, and cardiac arrest in 1 patient. None of the analyzed parameters (gender, ethnicity, age, comorbidities, severity of thrombocytopenia, thrombotic or bleeding events) was associated with ICU admission or early mortality. Patients\u27 platelet count before COVID-19 diagnosis did not differ from the platelet count at the time of COVID-19 diagnosis with a mean platelet count of 108.5 (+/- 49.0) and 93.8 (+/- 92.8) (p = 0.299), respectively. In addition, there was no significant difference in the platelet before COVID-19 and after recovery. Conclusion: Thrombocytopenia of chronic ITP patients did not worsen during COVID-19 infection or after recovery. Mortality of chronic ITP patients due to COVID-19 was not different from reported mortality of hospitalized COVID-19 patients. Our findings should be validated in larger cohorts
Correlation of PD-L1 expression, clinicopathologic and molecular characteristics in an array of solid tumors: A large-scale real world study
Background: Programmed death ligand-1 (PD-L1) is a predictive marker of anti-programmed death protein 1 (PD- 1)/PD-L1 therapies for solid tumors. Limited literature exists correlating PD-L1 expression, clinicopathological & molecular profiles. We aimed to 1) correlate PD-L1 immunohistochemistry (IHC) results with these profile across multiple solid tumors & 2) assess clinical outcomes (overall survival (OS) & disease-free survival (DFS)) of PD-L1 status with / without anti-PD-L1 immunotherapy (IT).
Design: All cases tested for PD-L1 IHC over 2 years (Aug 2019-Sep 2020) were retrieved for this study. Clinicopathological variables recorded included age, race, tumor type, type of PD-L1 clone, PD-L1 status (Tumor Proportion Score (TPS): negative:50%), Combined Positive Score (CPS): negative10), clinical stage, anti-PD-L1 IT. Microsatellite instability (MSI) status using IHC & Ploymerase chain reaction (PCR) assays was recorded. High PD-L1 was defined as PD-L1 expression of TPS \u3e50%/CPS\u3e10. Outcome studies included OS and DFS after generating Kaplan-Meier curves & compared using log rank test. Univariate analysis using Cox regression models were also used.
Results: There were 205 cases tested for PD-L1 by IHC. Cohort included non-small cell lung cancers (127), head & neck carcinomas (37), gastric or gastroesophageal carcinoma (20), kidney or urothelial carcinoma (16), cervical carcinomas (5). Median age was 70 years (range 28-90). Most were high stage cancers [stage 1: 5/205, stage 2: 5/205, stage 3: 30/205, stage 4 165/205]. PD-L1 IHC clones included: 22C3 (152/205), 28-8 (21/205) & both (32/205). High PD-L1 expression was observed in 52/205 (25.3%), out of which [37/127 (29.1%) were adenocarcinoma, 13/54 (24%) were squamous cell carcinoma, 2/24 (4.1%) others]. Anti PD-L1 IT was given in 65/205 (31.7%) patients. Anti PD-L1 IT was significantly associated with longer median survival OS (p=0.015) & DFS (p=0.004) (Figure 1). PD-L1 status was significantly associated with OS (p=0. 034) but not DFS (p=0. 076) (Figure 1). High PD-L1 had shorter median survival and higher hazards of death in OS (HR=5.4, CI-1.3-23.1) irrespective of IT. Association between three groups of PD-L1 status when compared with IT was statistically significant (p=0.048, Figure 2). PD-L1 & MSI testing was available in 29 patients & did not show any statistical correlation in this small cohort. No significant difference in survival for those received IT (4/29) vs no IT (25/29) & tested for both PD-L1 & MSI (OS: p= 0.277, DFS: p= 0.107).
Conclusions: This study supports the rational approach for PD-L1 therapy. High PD-L1 expression is more commonly seen in adenocarcinoma. Expression of high PD-L1 is associated with worse OS but not DFS. PD-L1 IT is significantly associated with longer median survival, OS & DFS. Larger, prospective studies are needed to support our findings
Cytological spectrum of granulomatous mastitis: diagnostic and treatment challenges
Background: Granulomatous mastitis (GM) is an inflammatory disease of the breast which clinico- radiologically mimics both inflammatory and malignant lesions. This leads to diagnostic dilemmas and delay in treatment. The aim of the present study was to review the cases diagnosed as granulomatous mastitis on Fine Needle Aspiration Cytology (FNAC) with an objective to co-relate their clinico-radiological findings, histology review where available and follow up treatment received to establish etiology and study the treatment outcome.Methods: Cytologically diagnosed cases of granulomatous mastitis were retrieved and reviewed from August 2015 - July 2017 records. Clinico-radiological co-relation, histology review where available and follow up treatment records were sought for.Results: Around 31.7% (530/1670) cases were reported as malignant, 60.3% (1009/1670) as benign proliferative and 7.9% (131/1670) as inflammatory lesions by breast FNA. 3.1% (51/1670) cases were reported as GM of all breast FNAC and 38% (51/131) of all inflammatory lesions. Follow up was available for 47 cases. Of which 26 (55.3%) cases were diagnosed as Tubercular Granulomatous mastitis (TGM) and 21(44.7%) were idiopathic granulomatous mastitis (IGM).Conclusions: Countries where tuberculosis is endemic, high degree of clinical suspicion and detailed work-up to rule out TGM is essential for all cases of granulomatous mastitis. Authors recommend a multidisciplinary workup with microbiological culture and molecular based tests on FNA material. This retrospective study illustrates that the cause of GM needs to be determined accurately for timely treatment, to avoid unnecessary delays and treatment dilemma in these patients
Legumes from the Paleocene sediments of India and their ecological significance
During the early Paleogene, greenhouse gases created warm global climates. These warm climates redistributed the habitat of marine and terrestrial biota globally. Understanding the ecology of biotas under extremely warm climates is important to decipher their behavior in future climate warming. Here we report two new legume fossils (Leguminocarpum meghalayensis Bhatia, Srivastava et Mehrotra sp. nov., and Parvileguminophyllum damalgiriensis Bhatia, Srivastava et Mehrotra sp. nov.) from the late Paleocene sediments of Tura Formation of Meghalaya, northeast India. Globally, the Paleocene legume fossil records indicate that legumes most likely immigrated to India from Africa via the Ladakh-Kohistan Arc during the early Paleogene. Moreover, previously reconstructed climate data from the Tura Formation indicate that legumes were well adapted to a warm seasonal climate with monsoon rains
An unusual case of external iliac artery thrombosis after renal transplant surgery
The rates of renal transplant for end stage renal disease are increasing worldwide. Vascular complications due to arterial thrombosis is seen only in less that 1% cases. We describe a case of 36 year old male who underwent a live-related renal transplant, whose post-operative period was complicated by juxta-anastomotic distal external iliac artery thrombosis. He was managed by thrombectomy and improved with complete recovery. Attention should be paid to anastomotic technique and prevention of formation of intimal flap. In case of arterial thrombosis, graft salvage can be attempted depending on the clinical scenario
Prognosis and categorization of HER2 fluorescent in-situ hybridization (FISH) results in patients with invasive breast cancer who received HER2 targeted agents: Analysis of 226 patients
Background: In management of invasive breast cancers (IBC), status of HER2 (ERBB2) gene serves as a strong prognostic predictor & predictive marker of response to HER2 Targeted Agents (HTA). There is significant heterogeneity in response to these agents in HER2- positive cases. Our aim was to determine the distribution of the status of HER2 by FISH in IBC along with its predictive implications. Design: IBC cases that were tested for HER2FISH & received HTA from 2006-2017 were identified. HER2FISH was interpreted using the ASCO/CAP guidelines at the time of reporting. Cases were grouped as follows: 1) Monosomy (ratio ≥2.0, mean HER2/cell\u3c4.0) 2) Co- Amplified (ratio\u3c2.0, mean HER2/cell ≥6.0) 3) Low amplified (ratio ≥2.0, mean HER2/cell 4.0-5.9) 4) Amplified (ratio ≥2.0-2.99, mean HER2/cell \u3e6) 5) Excessive Amplification (ratio ≥3.0) 6) 2013 Equivocal (ratio\u3c2.0, mean HER2/cell 4.0-5.9) 7) Negative. Outcomes studied were recurrence, metastasis, second breast primary, disease specific survival (DSS) & overall survival (OS). Results: There were 226 cases, with median age 65 (range 26-98), 58% Caucasians, 24% African Americans, 1.5% others & 16.5% unknown. The median HER2FISH ratio was 2.47 (1.18-21) & HER2 signal/cell 5.71 (2.09-21). Table 1 shows categoric distribution of cases. 60/226-27% patients received neoadjuvant chemotherapy, 139/226-62% hormonal therapy, 187/226-83% adjuvant & 146/226-65% radiotherapy. The median follow up was 207 weeks (4.3-708). Overall, 165/226-73% patients were alive without disease, 17/226-7% alive with disease, 33/226-15% died of IBC & 11/226-5% died due to other causes. 31/226-14% patients developed metastasis, 7/226-3% local recurrence & 4/226-2% second breast primary. The category of HER2FISH status was significantly associated with OS (p\u3c0.05-Figure1), higher HER2 amplification was associated with fewer deaths, possibly reflecting a better response to HTA. Her2FISH status also statistically significantly relates to metastasis (p=0.04-Figure 2) & second primary (p\u3c0.05) but not with recurrence (p=0.09) or DSS (p=0.5) in our cohort. (Table presented) Conclusions: The current HER2FISH interpretation does not stratify as high or low amplification based on FISH results. In our study, we demonstrate that high HER2 amplification is significantly associated with longer OS; these patients seem to benefit more from HTA. We recommend reporting these categories when assessing HER2FISH in IBC. Larger, prospective longitudinal studies are needed to validate our findings
Evaluation of HER2 fluorescent in-situ hybridization (FISH) status in 274 patients with invasive breast cancer: Comparison of the last 3 ASCO/CAP guidelines for fish interpretation and its effect on HER2 status classification
Background: HER2 gene status as a primary predictor of responsiveness to HER2-targeted therapies in invasive breast carcinomas (IBC), is assessed by in situ hybridization (ISH) for HER2 gene amplification or protein overexpression assessed by immunohistochemistry (IHC). We sought to access the influence of changes in HER2 FISH ASCO /CAP reporting guidelines from 2007, 2013 and 2018 on HER2 status. Design: This is a retrospective study of patients with IBC, who underwent HER2FISH testing between 2006 and 2017. At our institution, HER2 status is first determined by HER2IHC staining. All the HER2IHC equivocal (2+) cases are reflexed to HER2FISH. HER2FISH status was assessed by using Vysis dual FISH probe (Abbott Molecular, Inc., FDA Approved PathVysion HER-2 DNA Probe Kit). A comparative analysis was made based on 2007, 2013 and 2018 ASCO/CAP guidelines to assess HER2 status reclassification. Results: Complete data were available on 274 patients with equivocal HER2IHC results, 104 (38%) Caucasians, 52 (19%) African American, 4(1%) other, and 114 (42%) unknown. The results are summarized in tables 1-3 below. (Table presented) Conclusions: We observed 27.2% reclassification rate by using 2013 guidelines compared to 2007, lower threshold for positive (from equivocal, 20.7% of patients re-classified to positive and 6.5% to negative HER2 status). In contrast, the 2018 updates eliminated the FISH equivocal category with concomitant Her2IHC correlation and additional scoring of tumor nuclei. Implementing 2018 CAP guidelines led to 100% reclassification of 2007 equivocal cases into in 81.7% negative cases and 18.3% positive for HER2 status. Prospective data on survival is necessary to evaluate impact of 2018 guidelines on outcomes
Resolution of a modified CDC definition for carbapenem resistant enterobacteriaceae (CRE) using a rapid multiplex, cartridge-based molecular assay for the confirmation of carbapenemase genes
Background: CRE have emerged as a global threat due to their potential to cause invasive infections, often with high mortality rates and are primarily healthcare, associated, with a potential for spread to community settings. The CDC updated its definition of CRE as resistant to a carbapenem: MIC of ≥4 ug/ml for doripenem, meropenem, or imipenem, ≥2 ug/ml for ertapenem, OR documented to produce a carbapenemase. CRE are resistant to carbapenems primarily through the expression of carbapenemase genes (CP-CRE) carried on plasmids, which are easily transferrable hence the CDC recommendation to isolate patients with CP-CRE. However, production of AmpC/ESBL β-lactamases with a decrease of outer membrane proteins (OMP) (non-CP-CRE) can also lead to a higher ertapenem MIC, of which OMPs are not transferable but meet the CDC definition for CRE. The purpose of this study was to develop an algorithm to differentiate CP-CRE from non-CP-CRE using carbapenem MIC and confirmation by a rapid molecular assay. Design: Genetic and phenotypic testing was performed on 61 isolates of Enterobacteriaceae with MICs to ertapenem ranging from \u3c0.25 ug/ml to \u3e64 ug/ml using PCR to detect blaKPC, blaAmpC and blaESBL, and SDS-PAGE to determine OMP production. These data were used to create an algorithm to define CRE in our lab using MIC, the presence of resistance genes and/or OMP production. 40 isolates, including positive and negative controls, with known antibiotic susceptibilities were defined by this algorithm and confirmed by commercially available FDA approved rapid multiplex PCR for carbapenemase genes. Results: Using this algorithm, we observed 5 discordant PCR results giving us 85% concordance. However, we believe that 3 of these were due to loss of plasmids by repeated freeze-thaw cycles and intend to reanalyze MICs to confirm this. On eliminating these 3 isolates, we have 93% concordance.(Table presented) Conclusions: A combination of the CDC definition for CRE and lowered breakpoints to ertapenem led to overcalling non-CP-CRE as CPCRE may have resulted in inappropriate patient isolation, which is known to have negative patient outcomes and increase costs. Implementation of a multiplex PCR to rule out carbapenemases in isolates with elevated ertapenem but susceptible meropenem MICs resulted in a more sensitive and specific identification of CP-CRE