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Aim and Background: The aim of this study was to evaluate the prognostic value of imaging-based variables and tumor marker in predicting the progression-free survival (PFS) in treatment-naïve pancreatic cancer (PC) using baseline 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT). Materials and Methods: This retro-prospective study was conducted at PET/CT imaging facility of JCIA health-care facility of Pakistan. Total 68 patients with PCs were retrospectively included who had 18FDG PET/CT for staging from March 2017 to December 2020. Thirty-two patients had unresectable Stage IV disease on baseline imaging while the remaining 36 underwent Whipple's procedure and both categories were followed by chemotherapy with/without immunotherapy. These patients were followed for a median period of 18 months (1-62 months) for PFS. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used for independent predictors of patients' demographics, tumor characteristics, CA 19-9, and maximum standardized uptake value (SUVmax) in PFS. Kaplan-Meier's survival curves were analyzed to measure PFS using ROC-derived significant cutoff values of CA 19-9 and SUVmax. Results: Median PFS was 18 months (11-45) with 60% (41/68) patients were either died or labelled having metabolic progressive disease (MPD. Using logistic regression analysis, significant correlations were found for Stage IV disease and pancreatic body/tail tumor with disease progression (odd ratio: 7.535 and 4.803, respectively; P < 0.05). Gender, obesity, histological tumor type, and 18FDG-avid regional nodes did not show a significant impact on PFS. On ROC analysis, SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS (area under the curve: 0.827 and 0.911, respectively; P < 0.0001) and no association of age and primary tumor size in PFS. Significantly, shorter PFS was found using ROC-derived cutoff values of SUVmax >5.3 versus ≤5.3 of primary tumor (mean and 95% confidence interval [CI]: 16.7 vs. 48.5 and 10-23 vs. 41-56; log-rank = 25.014; P < 0.0001) and baseline CA 19-9 >197 versus ≤197 U/ml (mean and 95% CI: 11.8 vs. 46.9 and 7-16 vs. 39-55; log-rank = 38.217; P < 0.0001). Conclusion: SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS in treatment-naïve PC patients. Among demographics, only Stage IV disease and pancreatic tail and body tumors were found to have a negative association with disease progression.

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BACKGROUND:  In the current era vaccine-associated lymphadenopathy (VAL) is not an uncommon presentation on 18F-FDG PET/CT examinations in patients inoculated with Coronavirus disease 2019 (COVID-19) vaccination. In this study, we are presenting data of VAL on 18F-FDG PET/CT regarding its prevalence, temporal response to vaccination and imaging characteristics of VAL. METHODS: Seventy-eight (78) consecutive vaccinated breast cancer (BC) patients who had 18FDG PET/CT were retrospectively analyzed. All patients had COVID-19 vaccine shots in contralateral arms and none in breast cancer site axilla (BSA).  In 35 patients 18FDG avid nodes were found in vaccine site axilla (VSA). In 25 patients 18FDG avid nodes were found in BSA. Morphological criteria on CT images like size, presence of fatty hila and fat stranding of axillary nodes were analyzed. Metabolic criteria on PET images like SUVmax of nodes and liver as reference were also measured. RESULTS: Out of 78 patients, 35 had   positive nodes in VSA (45% prevalence) and 25/78 had BSA (33% prevalence). Mean duration of COVID-19 vaccination in each group was 8 ±04 week (non-significant p-value). On CT images, 18FDG avid nodes in VSA were significantly smaller (10 ± 03 mm) and with intact fatty hila without fat stranding than nodes in BSA with loss of fatty hila (25 ±10 mm; p <0.0001). Mean SUVmax of nodes in VSA was significantly lower (2.4 ±1.1) than nodes in BSA (10.2 ±5.5 - p-value <0.0001). Nodes in VSA showed a significant positive linear correlation between size and SUVmax (p-value 0.00001).  Similarly, nodes in VSA showed a significant negative linear correlation between duration and SUVmax (p-value 0.00003).  In VSA group, 03 patients having SUVmax >2 SD of Hepatic SUVmax were subjected to ultrasound guided fine needle aspiration (FNA) and turned out to be metastatic in nature. CONCLUSION: In COVID-19 vaccinated patients with BC, 18FDG avid nodes in VSA may pose diagnostic challenge. However, morphological (size < 10 mm short axis, intact fatty hila without fat stranding) and metabolic criteria (SUVmax <2.4 with negative correlation with time of inoculation) have higher diagnostic accuracy in resolving the dilemma. Nodes in VSA having SUVmax > 2 SD of hepatic SUVmax should be considered for FNA to rule out possible metastasis.

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Systemic mastocytosis (SM) is a relatively rare heterogeneous group of disorders characterized by uncontrolled proliferation and accumulation of clonal mast cells in one or more organs. Indolent SM is the most common variety. Less common variety is aggressive systemic mastocytosis (aSM) type with or without associated hematological neopalsm (AHN). Fludeoxyglucose (FDG) positron emission tomography/computed tomography has a limited role in aSM without AHN as these exhibit low FDG avidity. We are presenting a biopsy-proven case of aSM without AHN showing abnormally high FDG uptake in lesions involving skin, nodes, marrow, and muscles.

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Objective The purpose fo this prospective study was to find the impact of primary tumor size (Ts), standardized uptake values (SUVmax) of primary tumor, and the most avid neck node on disease recurrence in patients with head and neck oropharyngeal squamous cell carcinoma (HNOP-SCC). Material and methods We included patients with HNOP-SCC (without distant metastasis-M0 disease) who had pre- and post-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 FDG PET/CT) using strict standardized imaging protocol from 2017 to 2019. Based on follow-up ( 18 FDG PET/CT) findings, patients were categorized as disease free (no or minimal 18 FDG uptake ≤ background over surgical bed and no distant metastasis) and disease recurrence ( 18 FDG uptake > background over surgical bed with or without nodal and/or distant metastasis). Ts and SUVmax of primary tumor and the most avid neck node were compared and impact of these was studied upon disease recurrence. Results Total 112 patients were included. No significant difference was seen in mean age (overall: 60 ± 14 years), gender distribution (overall M:F: 69:31%), body mass index (overall: 25.20 ± 5.82), and history of diabetes (overall: 19%) between disease-free and disease recurrence groups. Similarly, no significant difference was observed for fasting blood sugar (overall: 110 ± 28 mg%), 18 FDG dose (overall: 169 ± 37 MBq), and uptake period (overall: 70 ± 12 minutes) between two groups ensuring strict adherence to standardized imaging protocol. Significant difference ( p < 0.05) was observed between disease-free and disease recurrence for Ts (25 ± 10 vs. 33 ± 14 mm), SUVmax of primary tumor (6.2 ± 6.8 vs. 9.3 ± 7.2) and the most avid neck node (2.1 ± 3.3 vs. 4.7 ± 5.9) and median follow-up (13 ± 12 vs. 08 ± 13 months), respectively. Using receiver operating characteristic analysis, Ts greater than 29 mm, baseline tumor SUVmax greater than 4.6, and nodal SUVmax greater than 6.2 were found independent predictors for disease recurrence. Nodal SUVmax greater than 6.2 was found an independent predictor of shortest disease-free survival (DFS) than Ts and tumor SUVmax. Conclusion We conclude that in HNOP-SCC, primary Ts (> 29 mm), SUVmax of primary tumor (> 4.6), and the most avid neck node (> 6.2) in baseline 18 FDG PET/CT using standardized imaging protocol are the independent predictors of disease recurrence. Furthermore, SUVmax greater than 6.2 of the most avid node predicts the shortest DFS than primary Ts and SUVmax of primary tumor.

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KEY MESSAGE: A major QTL for Hessian fly resistance was precisely mapped to a 2.32 Mb region on chromosome 3B of the US hard winter wheat cultivar 'Overland'. The Hessian fly (HF, Mayetiola destructor) is a destructive insect pest of wheat in the USA and worldwide. Deploying HF-resistant cultivars is the most effective and economical approach to control this insect pest. A population of 186 recombinant inbred lines (RILs) was developed from 'Overland' × 'Overley' and phenotyped for responses to HF attack using the HF biotype 'Great Plains'. A high-density genetic linkage map was constructed using 1,576 single nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). Two quantitative trait loci (QTLs) with a significant epistatic effect on HF resistance were mapped to chromosomes 3B (QHf.hwwg-3B) and 7A (QHf.hwwg-7A) in Overland, which are located in similar chromosome regions as found for H35 and H36 in the cultivar 'SD06165', respectively. QHf.hwwg-3B showed a much larger effect on HF resistance than QHf.hwwg-7A. Five and four GBS-SNPs, respectively, in the QHf.hwwg-3B and QHf.hwwg-7A QTL intervals were converted into Kompetitive allele specific polymerase chain reaction (KASP) markers. QHf.hwwg-3B was precisely mapped to a 2.32 Mb interval (2,479,314-4,799,538 bp) using near-isogenic lines (NILs) and RILs that have recombination within the QTL interval. The US winter wheat accessions carrying contrasting alleles at KASP markers KASP-3B4525164, KASP-7A47772047 and KASP-7A65090410 showed significant difference in HF resistance. The combination of the two KASP markers KASP-3B3797431 and KASP-3B4525164 is near-diagnostic for the detection of QHf.hwwg-3B in a US winter wheat panel and can be potentially used for screening the QTL in breeding programs.

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Neurolymphomatosis (NLS) is infiltration of lymphoma cells into the peripheral or cranial nervous system and is a rare manifestation of non-Hodgkin lymphoma (NHL). Nerve biopsy is considered as the gold standard for diagnosis but not a preferred choice, and magnetic resonance imaging has lower reported sensitivity. 18F-Fluorodeoxyglucose (18FDG) positron-emission tomography and computerized tomography (PET/CT) has a higher sensitivity for diagnosing and assessing the neurological and nonneurological metabolic tumor volume and response evaluation to therapy. We present the case of a lady, known to have NHL in remission. She presented with a short history of severe pain and weakness of the right lower limb. Baseline and interim 18FDG PET/CT played a crucial role in diagnosing and assessing the extent of NLS and nonneurological disease burden and also in evaluation of response to treatment.

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BACKGROUND: To determine progression free survival (PFS) and predictor of recurrence in patients with diffuse large B-cell lymphoma (DLBCL) with negative interim 18FDG PET/CT (iPET) using standardized imaging and reporting protocols. MATERIALS AND METHODS: This prospective study was conducted at PET/CT Section of a JCIA accredited healthcare facility from December 2015 till February 2020. Patients with DLBCL having complete metabolic response (CMR; Deauville score: 1-3) on iPET were selected and followed for a median period of 11 months (4-144 months).  End point response on follow-up PET/CT (either end of treatment or surveillance) was categorized as sustained CMR (sCMR) and disease recurrence. Kaplan Meier survival curve was used to measure PFS and receiver operating characteristics (ROC) was plotted for age, largest lesion size, highest standardized uptake value (SUVmax), disease stage and body mass index (BMI) on baseline scan to find their impact on recurrence. RESULTS: Total 185 patients with DLBCL who had achieved CMR on iPET with a median age 55 years (19 - 88 yr.) with male predominance (63% male) were selected. On follow-up, 123 (66%) had sCMR while recurrence was found in 34% (p <0.05). No significant difference in demographics was found between two groups. Median PFS time was 34 months (22.8 - 45.1 months). On ROC analysis, only baseline highest SUVmax was found as a significant independent predictor of disease recurrence at a cut off >22.6 (highest area under curve: 0.595; SE 0.046; p <0.05). CONCLUSION: We conclude that recurrence is found in 34% of DLBCL patients with a negative interim 18FDG PET/CT using standardized imaging and reporting protocols. Despite of early response, these patients need continued intensive follow-up especially those with a baseline SUVmax > 22.6.

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Carcinoma of unknown primary (CUP) is defined as biopsy proven tumor metastases that remains unidentified after a thorough diagnostic evaluation. The purpose of this study was to find the detection efficiency of 18F-flourodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) in patients with CUP. This prospective study was conducted at PET/CT Section of Department of Radiology, Aga Khan University Hospital Karachi, Pakistan from August 2017 to January 2018. Patients with a history of CUP referred for 18FDG PET/CT scan for detection of primary sites during the study were recruited. 18FDG PET/CT scan was acquired using standardized protocol, and patients with suspected primary sites underwent biopsies. Scan findings and biopsy results were analyzed to find the detection rate, sensitivity, area under curve (AUC), and positive predictive value (PPV). As no biopsy was performed in negative scan, true negative, and specificity could not be calculated. During the study, 46 consecutive patients with CUP were included. Mean age of cohort was 58 ± 17 years (63% male and 37% female) having a mean body mass index of 24.70 ± 4.97 kg/m2. Thirty-four patients (34/46) found to have a hypermetabolic focus suggestive of the primary tumor with known metastatic sites and subjected to biopsy which turned out to be positive in 26/34 patients (true positive). The primary tumor was detected in gastrointestinal and hepatobiliary in 8 (17%), head and neck in 6 (13%), genitourinary 4 (09%), lung 3 (06%), and miscellaneous sites in 5 (11%) patients. Detection rate, sensitivity and PPV of 18FDG PET/CT were 57%, 68%, and 76%, respectively. Remaining 12/46 patients with negative 18FDG PET/CT for primary focus did not have biopsy. Receiver operating character curve revealed fair diagnostic strength of 18FDG PET/CT for detecting unknown primary (AUC 0.667; P = 0.054; standard error = 0.083; confidence interval: 0.504-0.830). We conclude that 18FDG PET/CT is an effective tool for detecting primary tumor in patients with CUP and its upfront use could preclude the use of many futile diagnostic procedures. Furthermore, higher resolution scanners and acquiring delayed images in patients with negative study could reduce false-negative results in patients with CUP.

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Background: Precise staging of esophageal cancer (EC) is important for selection of optimal treatment option and prognostication. Aim of this study was to assess the role of 18FDG PET/CT in staging and response evaluation to neoadjuvant chemoradiation (nCR) in EC patients using standardized imaging protocol. Material and methods: This prospective study was conducted at PET/CT Section of Department of Radiology, Aga Khan University Hospital Karachi, Pakistan from July 2017 till February 2018. We included 34 biopsy proven EC patients who had 18FDG PET/CT and CT of neck, chest and abdomen as part of initial staging. Eleven patients had post-nCR 18FDG PET/CT using standardized imaging protocol as per EANM guidelines. CT and PET/CT based staging was compared. Based on PERCIST criteria, response evaluation was assessed using change in highest SUVmax (%ΔSUVmax) in baseline and follow-up scans (primary lesion, node or extra-nodal metastases). Results: Mean age of cohort was 57 ± 14 years (23 males and 11 females) having adenocarcinoma (AC) in 23 and squamous cell cancer (SCC) in 11 patients. Mean 18FDG dose, uptake time and hepatic SUVmean for baseline scans were 169 ±54 MBq, 65 ±10 minute and 1.91 ± 0.49 which were within ± 10%, ± 15% and ± 20% for follow-up scans in 11 patients respectively. Mean size (craniocaudal dimension in mm) and SUVmax of primary tumor was 56 ±27 mm and 13.4 ± 4.7. Based on 18FDG PET/CT findings, patients were categorized into N0 (10/34), N1 (09/34), N2 (11/34) and N3 (04/34) while 11/32 had stage IV disease. No significant difference was seen in AC and SCC groups. CT found stage IV disease in 3/34 (09%) while PET/CT found in 11/34 (32%; p value: 0.019) cases. PET/CT showed concordance with CT in 41% while discordance (all with upstaging) seen in 59%. On follow-up PET/CT, complete metabolic response was seen in 5/11 (45%) and partial metabolic response was noted in 6/11 (55% - p value non-significant) patients. Median %ΔSUVmax over primary lesions was 49.84% (-32.69 -100%) while over nodal sites it was 41.18% (-82.60 -100%). Conclusion: We conclude that 18FDG PET/CT was found a sensitive tool in initial staging of EC. Compared with CT, it had higher diagnostic accuracy for distant nodal and extra-nodal metastasis. %ΔSUVmax between baseline and post-nCR studies acquired with standardized protocol had changed management in more than half of our patients. For response evaluation in EC more studies with standardized 18FDG PET/CT imaging protocols are warranted.

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Tumors of the uterus are extremely uncommon. Pure lipomas of the uterus are very rare, and only a few cases have been reported. We are presenting a case of a post-menopausal lady, a survivor of right breast cancer who had an 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) for evaluation of a suspected right lung nodule. The scan was negative for hypermetabolic abnormality. However, a hypodense and non-metabolic lesion was seen in the fundus of the uterus. On subsequent hysterectomy, it was found to be a pure lipoma.

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The purpose of this prospective study was to determine metabolic response predictor(s) in propensity-matched patients having lymphomas who had baseline and interim 18fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) using strict standardized imaging and reporting protocols. This prospective study was conducted at PET/CT section of a JCI-accredited healthcare facility from April 2017 to February 2018. Patients with baseline and interim 18FDG PET/CT scans using standardized protocol were selected. Interim scans were performed not earlier than 2nd or later than 4th chemotherapy. During the study period, 97 of 112 consecutive patients with lymphomas (Hodgkin-HL: 32/97 and Non-Hodgkin-NHL: 65/97) were included in the study. Mean age of cohort was 45 ± 19 years (71% male and 29% female) having a mean body mass index (BMI) of 25.57 ± 5.54 Kg/m2 having Stage I (21%), Stage II (18%), Stage III (16%), and Stage IV (45%) disease. Bulky disease was found in 14% and 18FDG-avid marrow deposits in 33%. Standardized PET/CT imaging protocol as per EANM guidelines was strictly adopted for baseline and interim studies. %Δ changes in fasting blood sugar, 18FDG dose, uptake time, and liver SUV mean were 3.96%, 2.83%, 2.49%, and 12.15%, respectively. Based on Deauville's scoring, cohort was divided into responders having Score 1-3 (49/97) and nonresponders having Score 4-5 (48/97). The demographic analysis found no significant difference between responders and nonresponders for age, gender, BMI, staging, bulky disease or marrow involvement, and study protocol. No significant coefficient or odd ratios were found on multivariate analysis for age, gender, maximum standardized uptake value (SUVmax), size, BMI, NHL, and advance disease (Stage III and IV) in both groups (χ2: 5.12; receiver operating characteristic [95% confidence interval]: 0.616 [0.51-0.713]; P =0.528). Among responders, baseline SUVmax and tumor size had a direct correlation with a metabolic response on iPET, more pronounced in NHL than HL groups (SUVmax: 13.4 vs. 19.5 and size: 52 vs. 87 mm; P < 0.0001). We conclude that no significant predictor was found for response in propensity-matched patients with lymphomas (both HL and NHL) who had baseline and interim PET/CTs acquired with a standardized protocol. However, NHL responders were found to have higher baseline median SUVmax and larger lesion size as compared to HL responders. Although, these data are not in concordance with published findings but need to be validated with larger studies using standardized imaging and reporting protocols in propensity-matched patients with lymphomas.

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Meaningful change in bone mineral density (BMD) should be equal or higher than institutional least significant change (LSC). But some facilities use vendor's LSC which is discouraged by International Society for Clinical Densitometry (ISCD). The aim of this study was to find the impact of scan interpretation upon interval BMD changes using vendors and institutional LSCs. This prospective study was conducted at Joint Commission International-accredited facility of Pakistan from April-June 2017 using Hologic Discovery-A scanner. As per ISCD recommendations, precision error and LSC of two technologists were measured. Serial BMD changes such as deterioration or improvement interpreted based on vendor's and institutional LSCs were compared. Serial BMD changes in 102 patients were included, having a mean age, male:female ratio, and mean body mass index of 63 years, 94%:06%, and 29.274 kg/m2, respectively. Mean menopausal age was 47 years and mean duration between two dual X-ray absorptiometry (DXA) studies was 3 years. BMD changes over hip were found significant in 55% and 53% cases against vendor's and institutional LSCs, respectively (nonsignificant discordance in 2%). BMD changes using vendor's and institutional LSCs were found significant over L1-4 (62% vs. 46%; discordance: 14%) and distal forearm (77% vs. 35%; discordance: 41%), respectively. Interpretations based on vendor's LSCs revealed significantly overestimated deterioration over forearm and improvement over L1-4 BMD values. We conclude that vendor's provided LSC for interpretation of serial DXA is misleading and has a significant negative impact upon patients' management. Every DXA facility must use its own LSC as per ISCD guidelines. Furthermore, ISCD must consider publishing cutoff values for LSC for distal forearm measurement.

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Polylactic acid (PLA) is a biodegradable thermoplastic polyester. In 2010, PLA became the second highest consumed bioplastic in the world due to its wide application. Conventionally, PLA is produced by direct condensation of lactic acid monomer and ring opening polymerization of lactide, resulting in lower molecular weight and lesser strength of polymer. Furthermore, conventional methods of PLA production require a catalyst which makes it inappropriate for biomedical applications. Newer method utilizes metabolic engineering of microorganism for direct production of PLA through fermentation which produces good quality and high molecular weight and yield as compared to conventional methods. PLA is used as decomposing packaging material, sheet casting, medical implants in the form of screw, plate, and rod pin, etc. The main focus of the review is to highlight the synthesis of PLA by various polymerization methods that mainly include metabolic engineering fermentation as well as salient biomedical applications of PLA.