Reproducibility assessment of WHO reporting system for pancreaticobiliary cytopathology: A single institution experience.

BACKGROUND: The World Health Organization (WHO) reporting system for pancreaticobiliary cytopathology was released to internationalize the reporting, assisting in correct diagnosis and patient treatment with significant revisions from the previous Papanicolaou Society of Cytopathology (PSC) system. The "neoplastic: benign" and "neoplastic: other" categories have mostly been superseded by two new ones: "pancreatic neoplasia-low-grade" (PaN-low) and "pancreatic neoplasia-high-grade" (PaN-high), which classify intermediate neoplastic lesions based on cytological atypia. We aim to assess the reproducibility and risk of malignancy (ROM) for reporting pancreaticobiliary cytopathology by the WHO system in comparison with the PSC system. MATERIALS AND METHODS: A retrospective study by reviewing archival slides sent for pancreaticobiliary cytological evaluation from June 2021 to June 2023, by two pathologists blinded to each other's findings. Absolute ROM was determined by histopathology/cell block study/clinical follow-up (minimum 6 months)/overtly malignant imaging/metastasis. RESULTS: A total of 332 cases from 329 patients met the inclusion criteria, comprising pancreatic, gallbladder, and biliary lesions. The median patient age was 54 years (range, 14-86 years). The overall sensitivity of the test is 74.9% specificity is 93.2%, positive predictive value of 96.8%, negative predictive value of 57.6%, and a diagnostic accuracy of 81.8%. The absolute ROM for each site in all categories was comparable with that of the published data from the WHO system. CONCLUSION: Our study highlights the reliability of the WHO system for guiding clinical decision-making and patient management in the context of pancreaticobiliary. However, continual efforts among pathologists are essential to maintain consistent accuracy in cytological interpretations.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

Reliability of Emergency Department Diagnosis in Identifying the Etiology of Nontraumatic Undifferentiated Hypotension.

INTRODUCTION: Nontraumatic undifferentiated hypotension is one of the common and challenging critical presentations in the emergency department (ED) due to the difficulty in diagnosing the etiology of shock. In the present study, an attempt was made to test point-of-care ultrasound (PoCUS) as an early approach to improve the accuracy of diagnosis and to narrow the differentials in cases of nontraumatic undifferentiated hypotension. MATERIALS AND METHODS: This is a prospective explorative study conducted in the ED of a tertiary care hospital over a period of 18 months. A total of 100 patients were included in the study. All patients >18 years of age with systolic blood pressure <90 mm Hg with at least one sign or symptom of hypoperfusion were included in the study. Patients referred from another hospital as shock, history of trauma, and history suggestive of orthostatic hypotension and presented with symptomatic postural hypotension as the only chief complaint were excluded. All the patients who met the inclusion/exclusion criteria underwent detailed clinical and multi-organ PoCUS evaluation by two different observers. Assessment of the lungs, cardia, abdomen, aorta, inferior vena cava (IVC), and leg veins during the PoCUS examination was done. A third observer combined the clinical evaluation and the PoCUS findings. All patients were followed through for their final diagnosis at the time of discharge. First, the diagnosis after clinical evaluation alone was compared to the final diagnosis. Then the diagnoses based on the findings of PoCUS alone were compared with the final diagnosis. Last, the diagnosis obtained on combining the data of clinical evaluation with that of PoCUS was compared to the final diagnosis. The data were analyzed based on their reliability indices, accuracy, and the Cohen's kappa coefficient. RESULTS: Diagnoses based on clinical evaluation alone and POCUS alone were found to be accurate in 45% and 47% of patients, respectively. But on combining the findings of clinical evaluation with PoCUS, the accuracy increased to 89%. The most common etiology of shock was found to be distributive shock present in 38% of patients with sepsis being the most common subtype. In patients with obstructive shock, combined clinical evaluation with PoCUS was in perfect agreement with Cohen's kappa coefficient (κ) = 1 and those with distributive shock were in substantial agreement with Cohen's kappa coefficient (κ) = 0717. The overall kappa correlation of the combined evaluation with PoCUS was 0.89, which shows an almost perfect agreement with the final diagnosis. CONCLUSION: This study demonstrates the accuracy and reliability of PoCUS as an easy and valuable bedside tool when added to the clinical evaluation. It helps in narrowing the differentials and thereby guiding early goal-directed therapy in nontraumatic, undifferentiated hypotension patients presenting to the ED. HOW TO CITE THIS ARTICLE: Javali RH, Loganathan A, Srinivasarangan M, Akkamahadevi P, Ganesha BS, Nisarg S, et al. Reliability of Emergency Department Diagnosis in Identifying the Etiology of Nontraumatic Undifferentiated Hypotension. Indian J Crit Care Med 2020;24(5):313-320.

Fine-Needle Aspiration Cytology of Salivary Gland Lesions: A Revised Classification Based on "Milan System"-4years Experience of Tertiary Care Cancer Center of South India.

BACKGROUND: Fine-needle aspiration cytology plays role in preoperative diagnosis of any salivary gland mass lesions. Because of heterogeneity of salivary gland lesions and cytomorphology overlap, a uniform 6-tier Milan classification proposed which could be helpful in better communication of reports for patient's management. METHODS: Study included 4 years (2011-2015) retrospective data retrieval from cytology department of our Institute, which is a tertiary care cancer center of South India. Histopathology correlation was done wherever possible. RESULT: Total 253 cases were studied. Histopathological follow-up was available in 115 cases. Cases were categorized as nondiagnostic (1.58%), nonneoplastic (13.43%), benign (30%), atypia (0.8%), and suspicious for malignancy and malignant cytology (51.8%). The risk for malignancy was high for suspicious for malignancy and malignant cytological categories ranged from 96-100%. The sensitivity, specificity, and accuracy for diagnosing malignancy varied from 86.76%, 93.75%, and 89%, respectively. CONCLUSION: Risk stratification approach in classifying salivary gland cytology aspirate as per Milan system provides a standardized reporting and better communication to clinician.

Multifocal Osteosarcoma: Multiple Primaries or Metastases? A Report of Rare Case and Review of Literature.

INTRODUCTION: Multifocal osteosarcoma (MFOS) is characterized by multicentricity of osseous osteosarcomas, either synchronous or metachronous, without visceral involvement. They account for about 1.5% of all osteosarcomas. Most synchronous MFOS has one dominant lesion with one to four and very rarely five or more secondary lesions. The distal femur followed by the proximal tibia is the most common site of dominant lesions. Its prognosis remains extremely poor even with combined chemotherapy and surgery. CASE REPORT: We describe a rare case of MFOS in a 10-year-old boy who presented with a short history of severe aching pain in the right lower limb following a trivial fall. Initial workup and relevant investigations revealed a synchronous multicentric osteosarcoma with extensive involvement of appendicular and axial skeletal system. The dominant lesion was at the lower end of the right femur with multiple secondary lesions in the right tibia, left femur, bilateral humeri, pelvis, cervical and dorsolumbar spine, ribs, and sternum. The patient received one cycle of doxorubicin and cisplatin-based chemotherapy but unfortunately succumbed to progressive disease, a month after initiation of chemotherapy. CONCLUSION: MFOS is a very rare presentation of osseous osteosarcoma. The non-specific clinical manifestation, despite the presence of generalized skeletal involvement, presents a diagnostic difficulty for both the clinician and the radiologist. Only biopsy and histopathological examination can confirm the diagnosis of this highly malignant disease and help in proper management.

E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial- mesenchymal transition in bladder carcinoma.

BACKGROUND: Transcription factors are commonly deregulated in various cancers. Here, we evaluated role of ELF3 in pathogenesis of bladder carcinoma (BCa). MATERIALS AND METHODS: We confirmed ELF3 expression pattern in BCa cell lines using western blot; and in different grades of tumors using Immunohistochemistry. Cell invasion assay was employed to demonstrate potential role of ELF3 in EMT. RESULTS AND CONCLUSION: ELF3 showed selective expression in low-grade cell lines and tumor tissues. Overexpression of ELF3 in mesenchymal cell line UMUC3 resulted in reduced invasion and decreased expression of mesenchymal markers. We observed association of low ELF3 expression with increased risk and overall poor survival using publicly available data. ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer.

Comparison of Injury Severity Score, New Injury Severity Score, Revised Trauma Score and Trauma and Injury Severity Score for Mortality Prediction in Elderly Trauma Patients.

OBJECTIVES: This study tests the accuracy of the Injury Severity Score (ISS), New Injury Severity Score (NISS), Revised Trauma Score (RTS) and Trauma and Injury Severity Score (TRISS) in prediction of mortality in cases of geriatric trauma. DESIGN: Prospective observational study. MATERIALS AND METHODS: This was a prospective observational study on two hundred elderly trauma patients who were admitted to JSS Hospital, Mysuru over a consecutive period of 18 months between December 2016 to May 2018. On the day of admission, data were collected from each patient to compute the ISS, NISS, RTS, and TRISS. RESULTS: Mean age of patients was 66.35 years. Most common mechanism of injury was road traffic accident (94.0%) with mortality of 17.0%. The predictive accuracies of the ISS, NISS, RTS and the TRISS were compared using receiver operator characteristic (ROC) curves for the prediction of mortality. Best cutoff points for predicting mortality in elderly trauma patient using TRISS system was a score of 91.6 (sensitivity 97%, specificity of 88%, area under ROC curve 0.972), similarly cutoff point under the NISS was score of 17(91%, 93%, 0.970); for ISS best cutoff point was at 15(91%, 89%, 0.963) and for RTS it was 7.108(97%,80%,0.947). There were statistical differences among ISS, NISS, RTS and TRISS in terms of area under the ROC curve (p <0.0001). CONCLUSION: TRISS was the strongest predictor of mortality in elderly trauma patients when compared to the ISS, NISS and RTS. HOW TO CITE THIS ARTICLE: Javali RH, Krishnamoorthy et al. Comparison of Injury Severity Score, New Injury Severity Score, Revised Trauma Score and Trauma and Injury Severity Score for Mortality Prediction in Elderly Trauma Patients. Indian J of Crit Care Med 2019;23(2):73-77.

A Clinical Study on the Initial Assessment of Arterial Lactate and Base Deficit as Predictors of Outcome in Trauma Patients.

BACKGROUND: Trauma is a leading cause of mortality in India. Outcomes can be improved by early recognition of hemorrhagic shock and expedited management. At present, we rely on traditional vital signs, which are not sensitive measures. Point of care biochemical markers have been emerging as prognostic markers in trauma, but have not been studied in Indian setting. AIMS: This study aims to study the association between arterial lactate and base deficit (BD) at emergency department (ED) admission and 24 h outcome in trauma patients at risk of hemodynamic compromise. MATERIALS AND METHODS: This was a prospective observational study on 100 trauma patients at risk of hemodynamic compromise in tertiary care center ED. Arterial blood gas analysis at admission and 24 h outcomes were noted and statistically analyzed. RESULTS: Arterial lactate ≥4 mmol/L (sensitivity 100% and specificity 85.9%), BD ≥12 mEq/L (sensitivity 87.5% and specificity 82.6%) had more sensitivity than vital signs for predicting 24 h mortality. Higher lactate and BD were associated with increased blood transfusion requirement. Best cutoff values for predicting transfusion were lactate ≥2.9 mmol/L (sensitivity 65.2% and specificity 90.7%), BD ≥8 mEq/L (sensitivity 78.3% and specificity 75.9%). BD-based classification was comparable to ATLS classification in predicting mortality and determining transfusion requirements. Patients with higher arterial lactate and BD were found to have higher 24 h Intensive Care Unit (ICU) admission. CONCLUSION: Emergency admission arterial lactate and Base Deficit are useful predictors of mortality, need for blood transfusion and ICU admission at 24 h. It can be used to triage, identify shock early, assess transfusion requirement, and prognosticate trauma patients.

Studying Protocol-Based Pain Management in the Emergency Department.

BACKGROUND: Majority of the patients presenting to emergency department (ED) have pain. ED oligoanalgesia remains a challenge. AIMS: This study aims to study the effect of implementing a protocol-based pain management in the ED on (1) time to analgesia and (2) adequacy of analgesia obtained. SETTINGS AND DESIGN: Cross-sectional study in the ED. METHODS: Patients aged 18-65 years of age with pain of numeric rating scale (NRS) ≥4 were included. A series of 100 patients presenting before introduction of the protocol-based pain management were grouped "pre-protocol," and managed as per existing practice. Following this, a protocol for management of all patients presenting to ED with pain was implemented. Another series of 100 were grouped as "post-protocol" and managed as per the new pain management protocol. The data of patients from both the groups were collected and analyzed. STATISTICAL ANALYSIS USED: Descriptive statistical tests such as percentage, mean and standard deviation and inferential statistical tests such as Pearson coefficient, Student's t-test were applied. Differences were interpreted as significant when P < 0.05. RESULTS: Mean time to administer analgesic was significantly lesser in the postprotocol group (preprotocol 20.30 min vs. postprotocol 13.05 min; P < 0.001). There was significant difference in the pain relief achieved (change in NRS) between the two groups, with greater pain relief achieved in the postprotocol group (preprotocol group 4.6800 vs. postprotocol group 5.3600; P < 0.001). Patients' rating of pain relief (assessed on E5 scale) was significantly higher in the postprotocol group (preprotocol 3.91 vs. postprotocol 4.27; P = 0.001). Patients' satisfaction (North American Spine Society scale) with the overall treatment was also compared and found to be significantly higher in postprotocol group (mean: preprotocol 1.59 vs. postprotocol 1.39; P = 0.008). CONCLUSION: Protocol-based pain management provided timely and superior pain relief.

A rare case of translocation (12;22) (p13;Q) in Ewing's sarcoma.

Cytogenetic or immunohistochemical studies are often required to differentiate Ewing's sarcoma (ES) from other small round cell tumors. Herein we report a case of 13-year-old boy who presented with a large presacral lesion. Hemogram and biochemical parameters were normal except lactate dehydrogenase showing value of 96.40/IU/L, magnetic resonance imaging of the spine showed a large mass in presacral lesion (8 cm × 7 cm × 9 cm), with destruction of the sacrum (S2 S3 and S4) with interspinal extension. Bone scan showed multiple pelvic bone lesions, radiograph of chest, ultrasound of abdomen, pelvis and electrocardiogram were within normal limits. Bone marrow was not involved. Cells from the fine needle aspirate were cultured for short term using RPMI medium and karyotype obtained showed a t(12;22)(p12;q12) instead of the classic t(11;22). Diagnosis of ES was also confirmed by studies using immunohistochemistry for MIC2 which was positive, synaptophysin was inconclusive and leukocyte common antigen, desmin negative. This case provides evidence of the importance of chromosome 22, in the etiology of the disease.

Laryngeal paraganglioma: a rare clinical entity managed by supraselective embolization and lateral pharygotomy.

Laryngeal paragangliomas are benign slow growing tumors with symptoms resembling squamous cell carcinoma. Hoarseness or dysphasia are the commonest presenting symptoms and usually it presents as an submucosal mass on laryngoscopy. Ninety percentage of these tumors occur in the supraglottic larynx and the rest in the glottis and the subglottic region. Functional activity is seen in a few (2.9 %), none are associated with paraneoplastic syndromes. A 35-year-old male presented to us with hoarseness of voice since 4 months duration. Contrast arteriography demonstrated that the left superior thyroid artery supplied >80 % of the blood supply to the laryngeal mass. Supraselective embolization was done from the right femorals under local anaesthesia and sedation which was uneventfull. The tumor was excised from lateral pharyngotomy approach with an partial laryngectomy procedure. Microscopy and immune-histochemistry confirmed it to be paraganglioma. Complete surgical resection or partial laryngectomy with meticulous dissection of surrounding tissues and preservation of neurovascular structures gives an excellent prognosis as far as oncological clearance is concerned. Malignant paragangliomas of the larynx are rare and an major meta-analysis is necessary to provide a true biological behaviour of this tumor.