Novel computational biology modeling system can accurately forecast response to neoadjuvant therapy in early breast cancer.

BACKGROUND: Generalizable population-based studies are unable to account for individual tumor heterogeneity that contributes to variability in a patient's response to physician-chosen therapy. Although molecular characterization of tumors has advanced precision medicine, in early-stage and locally advanced breast cancer patients, predicting a patient's response to neoadjuvant therapy (NAT) remains a gap in current clinical practice. Here, we perform a study in an independent cohort of early-stage and locally advanced breast cancer patients to forecast tumor response to NAT and assess the stability of a previously validated biophysical simulation platform. METHODS: A single-blinded study was performed using a retrospective database from a single institution (9/2014-12/2020). Patients included: ≥ 18 years with breast cancer who completed NAT, with pre-treatment dynamic contrast enhanced magnetic resonance imaging. Demographics, chemotherapy, baseline (pre-treatment) MRI and pathologic data were input into the TumorScope Predict (TS) biophysical simulation platform to generate predictions. Primary outcomes included predictions of pathological complete response (pCR) versus residual disease (RD) and final volume for each tumor. For validation, post-NAT predicted pCR and tumor volumes were compared to actual pathological assessment and MRI-assessed volumes. Predicted pCR was pre-defined as residual tumor volume ≤ 0.01 cm3 (≥ 99.9% reduction). RESULTS: The cohort consisted of eighty patients; 36 Caucasian and 40 African American. Most tumors were high-grade (54.4% grade 3) invasive ductal carcinomas (90.0%). Receptor subtypes included hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+, 30%), HR+/HER2- (35%), HR-/HER2+ (12.5%) and triple negative breast cancer (TNBC, 22.5%). Simulated tumor volume was significantly correlated with post-treatment radiographic MRI calculated volumes (r = 0.53, p = 1.3 × 10-7, mean absolute error of 6.57%). TS prediction of pCR compared favorably to pathological assessment (pCR: TS n = 28; Path n = 27; RD: TS n = 52; Path n = 53), for an overall accuracy of 91.2% (95% CI: 82.8% - 96.4%; Clopper-Pearson interval). Five-year risk of recurrence demonstrated similar prognostic performance between TS predictions (Hazard ratio (HR): - 1.99; 95% CI [- 3.96, - 0.02]; p = 0.043) and clinically assessed pCR (HR: - 1.76; 95% CI [- 3.75, 0.23]; p = 0.054). CONCLUSION: We demonstrated TS ability to simulate and model tumor in vivo conditions in silico and forecast volume response to NAT across breast tumor subtypes.

Lymphoreticular malignancies in serous effusions: Cytomorphologic, flow cytometric and immunocytochemical analysis.

INTRODUCTION: Involvement of body fluids by lymphoreticular malignancies (LRM) is rare and often associated with poor prognosis and decreased overall survival. The present study was conducted to analyze the characteristic cytomorphologic, flow cytometric and immunocytochemical features of LRMs in serous effusions. MATERIALS AND METHODS: This was a three-year retrospective study. A total of 218 effusion samples, reported as involved by lymphoreticular malignancies, on cytology, were reviewed. All the cases wherein the cytological diagnosis was confirmed by flow cytometric (FCM) and/or immunocytochemical (ICC) studies were retrieved and studied in detail. FCM and/or ICC were performed in a total of 51/218(23.4%) samples, including 30 pleural (58.8%), 18 peritoneal (35.3%), and 3 pericardial fluid (5.9%) samples. RESULTS: The cytomorphologic diagnoses included infiltration by non-Hodgkin lymphoma (NHL;n = 27), infiltration by LRM (n = 19), infiltration by chronic lymphocytic leukemia (CLL;n = 2), Hodgkin's lymphoma (HL;n = 1) and suggestive of infiltration by LRM (n = 2). FCM and/or ICC confirmed the diagnoses as infiltration by T-cell lymphoblastic lymphoma in 18; mature B-cell NHL in 10; Burkitt lymphoma in 7; diffuse large B-cell lymphoma in 4; follicular lymphoma, T- cell NHL and CLL in 2 samples each and hairy cell leukemia, plasmablastic lymphoma and HL in 1 sample each. 94.1% concordance was noted between the initial and final cytologic diagnosis. CONCLUSIONS: Involvement of body fluids and effusions by LRMs, though rare, carries an immense prognostic significance and hence the prompt detection is crucial. Detection of these malignancies by cytologic examination of effusions is challenging yet potentially useful and the least invasive method available to establish an early diagnosis.

Utility of trans-vaginal ultrasound in diagnosis and follow-up of non-pregnant sexually active females with lower ureteric calculi.

OBJECTIVE: To assess the utility of trans-vaginal ultrasonography in evaluation of non-pregnant sexually active female patients with lower ureteric calculi. METHODS: A prospective study was done from January 2015 to December 2017 including non-pregnant sexually active females with suspected ureteric calculus. Trans-abdominal ultrasound was initially done in all patients. In those patients in whom trans-abdominal ultrasound was inconclusive or there was indirect evidence of lower ureteric calculus in form of ureteral dilation but no calculus was evident, trans-vaginal ultrasound was done. The patients with ureteric calculi detected on trans-vaginal ultrasound and kept on conservative management were also followed up with trans-vaginal ultrasound. Non-contrast computed tomography was done in patients with inconclusive trans-vaginal ultrasound. RESULTS: As per the study protocol, 156 out of the total 468 patients evaluated by trans-abdominal ultrasound were eligible for trans-vaginal ultrasound. Trans-vaginal ultrasound was done in 149 patients, as seven patients did not give consent. Seventy-nine patients were detected with a lower ureteric calculus on trans-vaginal ultrasound and 27 patients had gynecologic or other cause for their symptoms. Forty-three patients had an inconclusive trans-vaginal ultrasound of which 36 underwent non-contrast computed tomography, among them only one patient had a lower ureteric calculus. Stone free status could be easily demonstrated on follow-up trans-vaginal ultrasound. CONCLUSION: Trans-vaginal ultrasound in addition to trans-abdominal ultrasound is a very useful tool in evaluation of sexually active females with suspected lower ureteric calculus.

Upper Urinary Tract Adenocarcinoma Arising in Tubular Adenoma-A Rare Entity: Report of 2 Cases and Review of Literature.

Tubular adenoma of the urinary tract is a recently recognized entity, and there is a paucity of clinicopathological information. We describe 2 rare cases of adenocarcinoma of upper urinary tract arising in the background of tubular adenoma with high-grade dysplasia. The first case was an extremely uncommon combination of multifocal tubular adenomas involving ureter and renal pelvis and adenocarcinoma of kidney in a patient with renal calculi. The second case was of adenocarcinoma of kidney arising from tubular adenoma of renal pelvis in the right moiety of horseshoe kidney. There was no microsatellite instability. These findings indicate, probably, an adenoma-carcinoma pathway is also followed in the urinary tract similar to the gastrointestinal tract. To the best of our knowledge, no such observations are reported in the English literature previously.

Quick Sequential (Sepsis Related) Organ Failure Assessment: A high performance rapid prognostication tool in patients having acute pyelonephritis with upper urinary tract calculi.

Purpose: To analyze the utility of quick Sequential Organ Failure Assessment (qSOFA) in patients with uro-sepsis due to acute pyelonephritis (APN) with upper urinary tract calculi, we conducted this study. The role of qSOFA as a tool for rapid prognostication in patients with sepsis is emerging. But there has been a great debate on its utility. Literature regarding utility of qSOFA in uro-sepsis is scarce. Materials and Methods: Ours was a retrospective study including 162 consecutive patients who were admitted for APN with upper urinary tract calculi over a 3 and half years (total 42 months) period. We evaluated the accuracy of qSOFA in predicting inhospital mortality and intensive care unit (ICU) admissions and compared this with the predictive accuracy of systemic inflammatory response syndrome (SIRS). We used the Area Under Curve (AUC) of the Receiver Operator Characteristic curve to calculate it and also calculated the optimum cut off for qSOFA score. Results: The overall mortality and ICU admission rates were 7.4% and 12.9%, respectively. qSOFA had a higher predictive accuracy for in-hospital mortality (AUC, 0.981; 95% confidence interval [CI], 0.962-1.000) and ICU admissions (AUC, 0.977; 95% CI, 0.955-0.999) than SIRS. A qSOFA score of ≥2 was an optimum cut off for predicting prognosis. In a multivariate model qSOFA ≥2 was a highly significant predictor of in-hospital mortality and ICU admissions (p<0.001). Conclusions: qSOFA is a reliable and rapid bedside tool in patients with sepsis with accuracy more than SIRS in predicting inhospital mortality and ICU admissions.

Liquid biopsy: A new avenue in pathology.

Liquid biopsy is a relatively new entity. This non-invasive technique provides real-time information about a tumour. The liquid biopsy contains circulating tumour cells, cell-free DNA and exosomes. The main indications for liquid biopsy include early diagnosis, screening, detection of minimal residual disease, designing personalised treatment and predicting biological behaviour of the tumour. In this review, we discuss various aspects of liquid biopsy and compare it with conventional biopsy.

Facial Phaeohyphomycosis in an Immunocompetent Individual: A Rare Presentation of a Rare Fungus.

Phaeohyphomycosis is a rare mycotic infection caused by heterogenous groups of dematiaceous fungi involving the skin and subcutaneous tissue. Here, we report a case of cutaneous phaeohyphomycosis presenting as cauliflower-like verrucous lesion over the face in an immunocompetent individual. Histopathology showed suppurative granulomatous inflammation replete with pigmented broad fungal hyphae which is stained with periodic acid-Schiff stain, Grocott's methanamine silver stain, Schmorl's stain, and Masson-Fontana stain. Culture showed black-colored colonies identified as Exophiala spinifera.

Transcriptome and Metabolite analysis reveal candidate genes of the cardiac glycoside biosynthetic pathway from Calotropis procera.

Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG's were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair. Around 66.6% of unigenes were annotated by using various public databases and 5324 unigenes showed significant match in the KEGG database involved in 133 different pathways of plant metabolism. Further KEGG analysis resulted in identification of 336 unigenes involved in cardenolide biosynthesis. Tissue specific expression analysis of 30 putative transcripts involved in terpenoid, steroid and cardenolide pathways showed a positive correlation between metabolite and transcript accumulation. Wound stress elevated CG levels as well the levels of the putative transcripts involved in its biosynthetic pathways. This result further validated the involvement of identified transcripts in CGs biosynthesis. The identified transcripts will lay a substantial foundation for further research on metabolic engineering and regulation of cardiac glycosides biosynthesis pathway genes.