Natural history of spontaneous pancreatic portal vein fistulae: A systematic review of the literature.

BACKGROUND: Spontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation - varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes. METHODS: A search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria. RESULTS: A total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality. CONCLUSIONS: PPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis.

Molecular Survey of Tick-Borne Haemoparasites of Dogs by Multiplex Polymerase Chain Reaction from Punjab, India.

PURPOSE: Tick-transmitted parasites as Babesia gibsoni, Babesia vogeli, Ehrlichia canis, and Hepatozoon canis are major health concern for dogs. Owing to prevalence and infection severity, there is need of sensitive, specific, and affordable test for their simultaneous detection. METHODS: Prevalence of B. gibsoni, B. vogeli, E. canis, and H. canis infections was assessed on 719 blood samples by microscopy and multiplex PCR assay targeting 18S rRNA (B. gibsoni & H. canis), ITS1 & 5.8S rRNA (B. vogeli) and VirB9 gene (E. canis). An internal control (canine-actin) was also included to increase the accuracy of assay and effect of associated risk factors with disease prevalence was also studied. RESULTS: Microscopic prevalence of B. gibsoni, B. vogeli, E. canis and H. canis was 5.0%, 0.1%, 1.4% and 1.0%, respectively, whereas with multiplex PCR assay, the corresponding values were 8.9%, 1.1%, 2.6% and 5.1% besides concurrent infections of B. gibsoni & H. canis (0.4%), B. gibsoni & E. canis (0.4%), E. canis & H. canis (0.3%) and B. gibsoni & B. vogeli (0.1%). Analytical sensitivity of developed assay was 0.1pg (B. gibsoni & H. canis), 0.01pg (B. vogeli), and 1.0pg (E. canis). A ″fair″ (B. vogeli & H. canis) to ″substantial″ (B. gibsoni & E. canis) agreement between two tests was observed with data as statistically significant. Breed, sex and location were significantly associated with B. gibsoni infection. CONCLUSION: The developed multiplex PCR assay offers a potential solution to detect these pathogens simultaneously, aiding in timely diagnosis and effective disease management in suspected dogs.

COVID-19 and Cancer: A Comparison of the Two Important Pandemic Waves in an Indian Cancer Patients' Cohort.

Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves. This was a prospective study of all COVID-19-positive cancer patients attending our specialty out-patient department at Rajiv Gandhi Cancer Institute and Research Centre between March 2020 and November 2020 (1st wave) and April 2021 and June 2021 (second wave). All patients diagnosed to have COVID-19 by real-time polymerase chain reaction (RT-PCR) with a biopsy-proven solid organ malignancy attending the medical oncology out-patient department were included during both the waves. A total of 300 patients with proven SARS-CoV-2 infection by either RT-PCR or cartridge based nucleic acid amplification test were encountered, of which 123 were encountered during the first wave of the pandemic and 177 during the second wave. The case fatality rate of the first wave was 9.8%, with a 15-day case fatality rate of 5.6%, whereas for the second wave, it was 13% and 7.2%, respectively. Twelve patients succumbed to COVID-19 disease in the first wave and 23 succumbed in the second. There were no statistically significant correlations; however, the death in the second wave tended to occur more in younger male patients, with comorbidities and history of smoking. There was no relation with ongoing cancer-directed treatment or chemotherapy. Our study is unique in comparing characteristics of the two most important COVID-19 waves and treatment patterns in cancer patients from a single center. The second wave showed a higher CFR, hospital admission rate, and higher frequency of respiratory complications; however, there was no relation to cancer-directed therapy and COVID-19, thus reiterating the fact that cancer treatment should not be halted in the event of a COVID-19 infection.

Use of Oral Empagliflozin to Obtain Optimal Blood Sugar Levels for Conducting 18 F-FDG PET-CT in Patients with Hyperglycemia-A Pilot Study.

Background Flourine-18 fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET-CT) is a well-established imaging modality for the evaluation of patients with oncological and nononcological conditions. The underlying principle of imaging is the preferentially increased glucose consumption by cancer cells, due to overexpression of glucose type 1 receptors that are insulin independent. Thus, one of the factors that leads to decreased sensitivity of an 18 F-FDG PET-CT is elevated blood sugar levels, leading to decreased glucose uptake by cancer cells due to competitive inhibition. A significant percentage of patients scheduled for PET-CT scan has diabetes mellitus type II as a comorbid condition and often has elevated random blood sugar (RBS) precluding an upfront PET-CT evaluation. Such cases must be rescheduled. This causes delay in the evaluation and management of such patients. Empagliflozin is a novel sodium glucose type 2 inhibitor that prevents tubular reabsorption of glucose and increases renal glycosuria resulting in decreased blood sugar. This drug does not cause significant hypoglycemia or increase endogenous insulin secretion. This study was undertaken to evaluate a potential role for empagliflozin in facilitating optimal blood sugar control in patients with hyperglycemia on the day of the scheduled PET scan. Methods This is an interventional prospective study and patients detected to have RBS more than 200 mg/dL on the day of the scheduled scan were included in the study. The patients were administered two tablets of 10 mg empagliflozin and kept under observation. Samples for RBS were taken at approximately 2nd and 4th hour post administration by bedside method. These patients underwent scan on the same day after adequate sugar control and when an RBS of less than 200 mg/dL was achieved. The primary outcome studied was change in RBS values in the patient cohort and evaluation of PET SUV (standardized uptake value) compared with the rest of the patients scheduled on the same day. Secondary outcome was assessment of any side effects in the patients. Results Total of 10 patients were found to have elevated blood sugar (RBS > 200 mg/dL; irrespective of being on medication) and did not meet the evaluation criteria for a PET-CT scan on the scheduled day. Following administration of the drug, all 10 patients were able to attain blood sugar levels and fulfill the criteria for undergoing a PET-CT scan. No obvious side effect was noted in any of the patient. The SUV values of the patient cohort were comparable with the rest of the patient scanned on the day. Conclusion In this pilot study, 20 mg of empagliflozin (2 tablets of 10 mg) appears to be a safe and effective method for achieving optimal decrease in the RBS without causing hypoglycemia or hyperinsulinemia. It can be safely employed in the subset of population with RBS between 201 and 300 mg/dL to adequately bring the sugar levels at acceptable levels RBS less than 200 mg/dl and fulfill the FDG PET-CT criteria as per European Association of Nuclear Medicine (EANM) norms.

Structured training program on confocal laser endomicroscopy for pancreatic cystic lesions: a multicenter prospective study among early-career endosonographers (with video).

BACKGROUND AND AIMS: Data on how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs) are limited. Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. METHODS: Twenty-one early-career nCLE-naïve endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at 4 weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous versus nonmucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the criterion standard. Learning curves were determined using cumulative sum analysis. RESULTS: Accuracy and diagnostic confidence for differentiating mucinous versus nonmucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (P < .001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range, 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial interobserver agreement (κ = .63). Accuracy for nCLE-guided PCL subtype diagnoses ranged from 82% to 96%. The learned nCLE skills did not deteriorate at 8 weeks and were not impacted by a refresher session. CONCLUSIONS: We developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Pancreatic Malakoplakia: A Rare Pathology Associated With Acute Pancreatitis.

Malakoplakia is a rare granulomatous tumor-like inflammatory condition, most frequently involving the genitourinary system and occurring in immunosuppressed patients. The gastrointestinal tract is the second most common site, where it is usually seen involving the colon. We report a case of malakoplakia presenting as a pancreatic mass. Imaging showed soft tissue along the pancreatic tail/greater curvature concerning for infiltrating tumor, but endoscopic ultrasound with biopsy showed malakoplakia. Our case discusses malakoplakia at an uncommon site, which was appropriately treated with antibiotics.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

KRAS mutated Non-Small Lung Carcinoma: A Real World Context from the Indian subcontinent.

BACKGROUND: KRAS, although a common variant of occurrence (~20% of non-small-cell lung carcinoma [NSCLC]) has been untargetable, owing to the molecular structure which inherently prevents drug binding. KRAS mutations in NSCLC are associated with distinct clinical profiles including smokers and mucinous histology. KRAS G12C mutations account for ~40% KRAS altered NSCLC, but NSCLC being a geographically diverse disease, the features may be distinct in this part of the world. This is a single-center experience of KRAS-mutated NSCLC including clinical, imaging, pathologic features, and treatment patterns and outcomes. METHODS: This is a single-center retrospective study of KRAS-mutated NSCLC. The clinicopathological features and outcomes were retrieved and collated from the medical record archives of the hospital. RESULTS: Fifty (30.6%) patients with advanced-stage NSCLC with alterations in the KRAS gene were enrolled in the 163 patients who were tested for KRAS alterations. The median age was 61 years. Molecular detection revealed three main types of KRAS mutations viz-a-vis: G12C in 17 (34%), G12V in 9 (18%), and G12D in 6 (12%) patients. Comparing G12C versus the non-G12C mutated cases, co-mutations were common in the non-G12C subgroup (p < 0.05). Among the 36, who were treated at our center, all received chemotherapy as the first line with a median progression-free survival (PFS)of 5.4 months. The PFS of G12C was higher than the non-G12C subgroup (6.4 vs 3.8 months). CONCLUSION: This is the largest single-center experience from the Indian subcontinent for KRAS-mutated NSCLC with distinct clinical features. It highlights the unmet need for G12C inhibitors in our country, where prevalence is equivalent to the West.

In vitro acaricidal activity of Piper longum L. against amitraz resistant Rhipicephalus microplus (Acari: Ixodidae).

The cattle tick, Rhipicephalus microplus Canestrini (Acari: Ixodidae) is one of the most important tick species severely affecting health and causes huge losses to dairy industry. Chemical acaricides are mainly applied for tick control but development of resistance, environmental pollution and contamination of milk and meat products with residues has led to exploration alternative eco-friendly tick control strategies. The dried fruits of Piper longum L. (Indian long pepper, Thippali or Pippali) generally used as flavoring agent have also been shown to have insecticidal property. Different concentrations (0.625%-10%) of alcoholic and aqueous extracts of Piper longum L. were prepared and evaluated for acaricidal activity against amitraz resistant R. microplus adult and larval stages. Against larval stages a dose-dependent mortality response was recorded for both extracts and higher acaricidal property was exhibited by the alcoholic extract with LC50 and LC95 (95% CL) values of 0.488% (0.48-0.49) and 1.39% (1.35-1.44), respectively. Similarly, against adult engorged females, ethanolic extract showed higher acaricidal property with LC50 and LC95 (95% CL) values of 4.67% (4.61-4.74) and 12.38% (12.05-12.73), respectively. Significant (p < 0.05) reduction was recorded in reproductive index of ticks treated and but no effect on hatchability of eggs was recorded in treated groups. The present study establishes acaricidal activity of P. longum fruit extracts against both larval and adult stages of amitraz resistant population of cattle tick.

Duplex real-time PCR methods for molecular detection and characterization of canine tick-borne haemoparasites from Punjab state, India.

BACKGROUND: Microscopy is a routinely used technique for the diagnosis of canine tick-borne haemoparasitic diseases in various clinical laboratories worldwide. In an attempt to provide better diagnostic assay to the clients for effective management of these diseases duplex real-time PCR assays were applied. METHODS AND RESULTS: Blood samples (n = 338) aseptically collected from suspected dogs of Central Plain Zone of Punjab state, India were subjected to SYBR Green based real-time duplex PCR assays for simultaneous detection of B. vogeli & E. canis and B. gibsoni & H. canis. Results revealed an overall prevalence rate of canine tick-borne haemoparasites as 54.1%, amongst which H. canis was the predominant (25.4%), followed by B. gibsoni (16.3%), E. canis (10.7%) and B. vogeli (1.8%). Sensitivity and specificity of the duplex assays ranged from 59.04 to 100.0% and 58.12 to 92.52%, respectively and their strength of agreement was ″fair″ with kappa value statistics. A significant (p < 0.05) association between prevalence of B. gibsoni, H. canis and E. canis infection with risk factors like sex, breed, season and location was recorded. The ancestral background of the field isolates of haemoparasites was also studied by phylogenetic analysis of their nucleotide sequences. CONCLUSIONS: SYBR Green dye based duplex real-time PCR assays proved to be highly sensitive, specific, rapid and affordable diagnostic tests for use by clinicians to save the life of pets.

Development and validation of multiplex SYBR Green real-time PCR assays for detection and molecular surveillance of four tick-borne canine haemoparasites.

Two multiplex SYBR Green based real-time PCR assays were standardized and evaluated to detect DNA from four canine haemoparasites (Babesia gibsoni, Babesia vogeli, Ehrlichia canis and Hepatozoon canis), along with internal controls from dogs from selected districts of Punjab state, India. Amplicons of 126 bp, 337 bp, 234 bp and 106 bp corresponding to B. gibsoni (18S rRNA gene), B. vogeli (18S rRNA gene), E. canis (virB9 gene), and H. canis (18S rRNA gene) were obtained, without any non-specific amplification. Microscopic evaluation of 200 blood samples from dogs revealed the prevalence of B. gibsoni, E. canis and H. canis as 1.5%, 1.5% and 1.0%, respectively, while with the multiplex real-time PCR assays the values for B. gibsoni, B. vogeli, E. canis, and H. canis were 8.0%, 1.5%, 3.5% and 23.5%, respectively, with concurrent infections of B. gibsoni and H. canis (3.5%); E. canis and H. canis (2.0%) and B. gibsoni, B. vogeli, E. canis, and H. canis (0.5%). The diagnostic sensitivity of the multiplex real-time PCR assays with respect to microscopy in the detection of B. gibsoni, E. canis and H. canis was 100% while the specificity for B. gibsoni, B. vogeli, E. canis, and H. canis was 93%, 100%, 98% and 77%, respectively, revealing the respective strength of agreement as ″fair″, ″slight″, ″moderate″ and ″slight″ by kappa value statistics, and the data were statistically significant, for detection of B. gibsoni and E. canis infections, by Fisher's exact test. The analytical sensitivity of the multiplex PCR assays in detection of DNAs was 8.59 × 105 and 9.9 × 106 copies for B. vogeli and E. canis, respectively, and 1.15 × 106 and 3.41 × 105 copies for B. gibsoni and H. canis, respectively. Assessment of risk factors viz. age, sex, breed, season and locations showed no significant association with the prevalence of these haemoparasites except for B. vogeli, E. canis and H. canis where significant associations were found for location, age and breed, respectively by multiplex real-time PCR assays.

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

EGFR detection by liquid biopsy: ripe for clinical usage.

Introduction: With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. Methods: 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019-2020. Results: Of 184 cases, 70 were positive by Cobas, 51 by ddPCR and 69 by Therascreen. The sensitivity of Cobas was 97.1% and the sensitivity of ddPCR was 71%. Receiver operating characteristic analysis showed an area under the curve of 0.977 for Cobas and 0.846 for ddPCR. Conclusion: In line with the FLAURA trial of osimertinib making its way to first-line and given the IASLC recommendations, it is important to understand the attributes of these tests to initiate appropriate treatment.

Lay abstract Lung cancer is one of the most common malignancies and has been known to have a dismal outcome. However, owing to evolution in the knowledge of disease biology and processes, many molecules have been discovered that can be used in targeted therapy. To institute this modality of treatment, detection of alterations in these specific molecules, namely: EGFR, ALK, ROS1, RET, MET, KRAS G12C, BRAF V600E, NTRK1, NTRK2, NTRK3 and ERBB2 is necessary. This has traditionally been done using single-gene assays, which require more tissue. This is a major limitation in cases of non-small cell lung carcinoma, as the biopsies are small. Hence, new technologies like next-generation sequencing have emerged that offer a one-stop solution for these cases. In cases where tissue is very scant, the use of peripheral blood has now been recommended by international guidelines for primary detection of these molecular alterations. This article describes the concordance of tissue-based detection and blood-based detection using three different assays, for the detection of EGFR alterations. Although promising results were obtained largely for blood-based assays, liquid and tissue biopsies are complementary.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome.

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

Enrichment of Zinc and Iron Micronutrients in Lentil (Lens culinaris Medik.) through Biofortification.

Biofortification of pulse crops with Zn and Fe is a viable approach to combat their widespread deficiencies in humans. Lentil (Lens culinaris Medik.) is a widely consumed edible crop possessing a high level of Zn and Fe micronutrients. Thus, the present study was conducted to examine the influence of foliar application of Zn and Fe on productivity, concentration, uptake and the economics of lentil cultivation (LL 931). For this, different treatment combinations of ZnSO4·7H2O (0.5%) and FeSO4·7H2O (0.5%), along with the recommended dose of fertilizer (RDF), were applied to the lentil. The results of study reported that the combined foliar application of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at pre-flowering (S1) and pod formation (S2) stages was most effective in enhancing grain and straw yield, Zn and Fe concentration, and uptake. However, the outcome of this treatment was statistically on par with the results obtained under the treatment ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage. A single spray of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage enhanced the grain and straw yield up to 39.6% and 51.8%, respectively. Similarly, Zn and Fe concentrations showed enhancement in grain (10.9% and 20.4%, respectively) and straw (27.5% and 27.6% respectively) of the lentil. The increase in Zn and Fe uptake by grain was 54.8% and 68.0%, respectively, whereas uptake by straw was 93.6% and 93.7%, respectively. Also the benefit:cost was the highest (1.96) with application of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage. Conclusively, the combined use of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage can contribute significantly towards yield, Zn and Fe concentration, as well as uptake and the economic returns of lentil to remediate the Zn and Fe deficiency.

Synchronous Detection of Extra-Adrenal Paraganglioma in a Follow-Up Case of High-Grade Gastrointestinal Stromal Tumor.

Extraadrenal paragalionoma at multiple sites and its association with GIST is a rare finding. Although 18F-FDG PET-CT is not a modality of choice for primary diagnosis of paraganglioma, and its use is restricted for detection of metastases/multiple sites and disease staging. However, in this case that we describe here, its role in an already-proven/recurrent case of paraganglioma is emphasized by its simultaneous assessment of disease at several different sites.

Pancreatic-Portal Vein Fistula: a Rare Diagnosis with Wide-Ranging Complications-13-Year Experience of a Pancreas Center of Excellence.

PURPOSE: To determine factors affecting mortality, and long-term patency of portal vein, in patients with pancreatic-portal vein fistula (PPVF). METHODS: Consecutive cases of PPVF at the University of Pittsburgh Medical Center from 2008 to 2020 were retrospectively identified. Clinical history, imaging studies, management strategies, complications, and long-term outcomes were analyzed. RESULTS: Fourteen patients, representing the largest PPVF cohort reported to date (mean age 58.6 years, 64.3% women, median follow-up 10 months [1-98 months]) were identified. Underlying chronic pancreatitis was seen in 9 (64.3%) patients, while 5 (35.7%) developed PPVF with first attack of acute pancreatitis. PPVF involved proximal main portal vein (MPV) in 10 (78.6%) patients. Of the 5 patients (35.7%) who died, all had occlusive (n=4) or near-occlusive (n=1) PPVF-associated filling defect (FD) in the MPV. Conversely, 7 of 9 survivors (87.5%) had subocclusive FD and patent MPV. In patients with sepsis (n=5), 1 underwent surgical necrosectomy and survived, while 3 of 4 (75%) patients without debridement died. CONCLUSION: Occlusive/near-occlusive PPVF-associated MPV FD, and sepsis, are associated with high mortality rates, while subocclusive MPV FD is associated with survival and long-term MPV patency. PPVF is a potentially life-threatening, and possibly under-diagnosed, entity that warrants early clinical suspicion for timely diagnosis, to facilitate optimal management.