Gallbladder Lesions Research Articles

Negative 18F-FDG and Positive 68Ga-FAPI-04 Findings in a Patient With Acute Exacerbation of Chronic Cholecystitis.

Acute cholecystitis typically exhibits intense FDG uptake of the gallbladder wall. Radiolabeled fibroblast activation protein inhibitor (FAPI) is considered as a potential alternative agent for tumor-specific imaging. We report 18F-FDG and 68Ga-FAPI-04 PET/MR findings in a 44-year-old woman with acute exacerbation of chronic cholecystitis. The lesions show negative 18F-FDG uptake but intense 68Ga-FAPI-04 uptake in PET/MR. This case highlights the imperative for nuclear medicine clinicians to exercise vigilance when evaluating gallbladder lesions exhibiting intense 68Ga-FAPI-04 but negative 18F-FDG uptake.

Update on the Role of Imaging in the Diagnosis, Staging, and Prognostication of Gallbladder Cancer

AbstractGallbladder cancer (GBC) is a highly aggressive malignancy with dismal prognosis. GBC is characterized by marked geographic predilection. GBC has distinct morphological types that pose unique challenges in diagnosis and differentiation from benign lesions. There are no specific clinical or serological markers of GBC. Imaging plays a key role not only in diagnosis and staging but also in prognostication. Ultrasound (US) is the initial test of choice that allows risk stratification in wall thickening and polypoidal type of gallbladder lesions. US findings guide further investigations and management. Computed tomography (CT) is the test of choice for staging GBC as it allows comprehensive evaluation of the gallbladder lesion, liver involvement, lymph nodes, peritoneum, and other distant sites for potential metastases. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography allow better delineation of the biliary system involvement. Contrast-enhanced US and advanced MRI techniques including diffusion-weighted imaging and dynamic contrast-enhanced MRI are used as problem-solving tools in cases where distinction from benign lesion is challenging at US and CT. Positron emission tomography is also used in selected cases for accurate staging of the disease. In this review, we provide an up-to-date insight into the role of imaging in diagnosis, staging, and prognostication of GBC.

Practical approach to linear endoscopic ultrasound examination of the gallbladder

The gallbladder (GB) is a susceptible organ, prone to various pathologies that can be identified using different imaging techniques. Transabdominal ultrasound (TUS) is typically the initial diagnostic method due to its numerous well-established advantages. However, in cases of uncertainty or when a definitive diagnosis cannot be established, computed tomography (CT) or magnetic resonance imaging may be employed to provide more detailed information. Nevertheless, CT scans may sometimes offer inadequate spatial resolution, which can limit the differentiation of GB lesions, particularly when smaller yet clinically relevant abnormalities are involved. Conversely, endoscopic ultrasound (EUS) provides higher frequency compared to TUS, superior spatial resolution, and the option for contrast-enhanced harmonic imaging, enabling a more comprehensive examination. Thus, EUS can serve as a supplementary tool when conventional imaging methods are insufficient. This review will describe the standard EUS examination of the GB, focusing on its endosonographic characteristics in various GB pathologies.

Risk score for malignancy in patients with suspicious gallbladder lesions: Retrospective analysis of 175 cases.

Among cancers, carcinoma gallbladder has one of the most dismal prognosis. Early lesions are difficult to biopsy because of proximity to luminal structures and risk of biliary peritonitis. However, early surgery offers the only chance of a complete cure. Utilizing a risk score would allow characterization of the risk of malignancy and early referral to an oncology centre thereby resulting in better outcomes for patients with carcinoma gallbladder. The aim of this study was to develop a risk score for carcinoma in patients with suspicious gallbladder lesions based on clinical presentation and imaging. All patients with suspicious gallbladder lesions on radiological imaging who underwent surgery were analyzed. Patients were considered for scoring if the ultrasound showed the gallbladder wall thickening (more than 4mm) and computed tomography scan showed operable disease. Statistical analysis was done to derive a score for malignancy. Total 175 patients underwent an operation for suspicious gallbladder lesions from January 2005 to December 2014. The factors analyzed were clinical biochemical and imaging findings. Of these, 71 were benign on the final histopathology and 104 were malignant. The score was constructed with the following variables: female sex, high total bilirubin (≥ 1mg/dL), presence of a mass, focal location of the lesion, presence of gallbladder stones and nodal involvement in the hepatoduodenal region on imaging. A model score and modified score were obtained. In this modified score, score of more than 8 out of 20 predicted malignancy with a sensitivity of 78% and specificity of 70.4%. Receiver operating characteristic (ROC) curve constructed with these variables had an area under curve of 0.828. There was no statistically significant difference between the model score and the modified score. A pre-operative risk score was obtained for carcinoma gallbladder, which needs to be validated prospectively in future.

Transabdominal ultrasound evaluation of vascularity of gallbladder lesions: particularly those with wall thickening.

Gallbladder wall thickening is relatively common in clinical settings, and for appropriate diagnosis, the size, shape, internal structure, surface contour, and vascularity of the gallbladder wall must be evaluated. Morphological evaluation is the most important; however, some gallbladder lesions resemble gallbladder cancer in imaging studies, making differential diagnosis challenging. Vascular evaluation is indispensable for a precise diagnosis in these cases. In this review, we present the current status of vascular evaluation using US and diagnosis using vascular imaging for gallbladder lesions, including those presenting with wall thickening. To date, several ultrasound imaging techniques have been developed to assess vascularity, including Doppler imaging with high sensitivity, use of contrast agents, and microvascular imaging using a novel filter for Doppler imaging. Although conventional color Doppler imaging is rarely used for the diagnosis of gallbladder lesions, the efficacy of contrast-enhanced ultrasound in assessing the vascularity, enhancement pattern, or timing of enhancement/washout has been reported. Presence of multiple irregular microvessels has been speculated to indicate malignancy. However, few reports on microvessels have been published, and further studies are required for the precise diagnosis of gallbladder lesions with microvascular evaluation.

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

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. 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. 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. 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.

Coagulation and fibrinolytic markers offer utility when distinguishing between benign and malignant gallbladder tumors: A cross-sectional study

BackgroundThe metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. MethodsThis study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. ResultsThe average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. ConclusionsIn gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.

Discrimination between benign and malignant gallbladder lesions on enhanced CT imaging using radiomics.

Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.

Contributions of endoscopic ultrasonography-guided tissue acquisition (EUS-TA) to the diagnostics of biliary stricture and gallbladder lesions.

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.

EUS-guided FNA and biopsy for cytohistologic diagnosis of gallbladder cancer: a multicenter retrospective study

EUS-guided FNA and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer (GBC). The aim of this study was to investigate the efficacy and safety of EUS-FNAB for patients with suspected GBC. Data were analyzed from patients who underwent EUS-FNAB for suspected GBC in 3 hospitals between 2010 and 2023. The diagnostic performance and safety of EUS-FNAB according to characteristic factors were calculated and compared. Of 170 patients, 163 had GBC. EUS-FNAB samples were obtained from the GB in 125 patients and sites other than the GB in 45 patients. The overall sensitivity, specificity, and accuracy were 83.4%, 100%, and 84.1%, respectively. The sensitivity and accuracy for patients with GB samples were 80.8% and 81.6%; for patients without GB samples, these values were 90.7% and 91.1%. The sensitivity and accuracy were higher with fine-needle biopsy needles than with FNA needles and with≤22-gauge needles than with 25-gauge needles. However, no significant differences were observed between the GB and lymph node samples. GB lesions<40mm in size, wall-thickening type, fundal location, absence of extensive liver invasion, and distant metastasis were more frequent in patients without GB samples than in patients with GB samples. Four mild bleeding events were the only reported adverse events. EUS-FNAB was safe and showed high diagnostic performance for patients with suspected GBC, regardless of the target site. When appropriate GB targeting is difficult, targeting the lymph nodes would be a good strategy with comparable outcomes.

Contrast Enhanced CT Versus MRI for Accurate Diagnosis of Wall-thickening Type Gallbladder Cancer

IntroductionDiagnosis of wall-thickening type gallbladder cancer (GBC) is challenging. Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly utilized to evaluate gallbladder wall thickening. However, there is a lack of data comparing the performance of CT and MRI for the detection of wall-thickening type GBC. AimWe aim to compare the diagnostic accuracy of CT and MRI in diagnosis of wall-thickening type GBC. Materials and MethodsThis prospective study comprised consecutive patients suspected of wall-thickening type GBC who underwent preoperative contrast-enhanced CT and MRI. The final diagnosis was based on the histopathology of the resected gallbladder lesion. Two radiologists independently reviewed the characteristics of gallbladder wall thickening at CT and MRI. The association of CT and MRI findings with histological diagnosis and the interobserver agreement of CT and MRI findings were assessed. ResultsThirty-three patients (malignancy, 13 and benign, 20) were included. None of the CT findings were significantly associated with GBC. However, at MRI, heterogeneous enhancement, indistinct interface with the liver, and diffusion restriction were significantly associated with malignancy (p=0.006, <0.001, and 0.005, respectively), and intramural cysts were significantly associated with benign lesions (p=0.012). For all MRI findings, the interobserver agreement was substantial to perfect (kappa=0.697-1.000). At CT, the interobserver agreement was moderate to near perfect (k=0.631-1.000). ConclusionThese findings suggest that MRI may be preferred over CT in patients with suspected wall thickening type GBC. However, larger multicenter studies must confirm our findings.

Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis.

Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB.

Hepatic arterial infusion chemotherapy combined with bevacizumab plus a PD-1 inhibitor for gallbladder cancer with hepatic oligometastasis: a real-world study.

Gallbladder cancer (GBC) is different from other biliary tract cancers in terms of molecular phenotype and microenvironment. Specific treatments for GBC need to be urgently explored. This study preliminarily investigated the clinical value of hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab plus a programmed death receptor-1 (PD-1) inhibitor for treatment of GBC with hepatic oligometastasis. We retrospectively collected data on GBC patients with hepatic oligometastasis, who received this combination therapy. The clinical data, conversion rate, treatment response, adverse events (AEs), and short-term survival were summarized. The responses of primary gallbladder lesions and hepatic metastasis, and their effect on prognosis, were investigated. A total of 27 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 55.6% and the disease control rate (DCR) was 85.2%. Median overall survival (OS) time was 15.0 months and the 1-year survival rate was 64.0%. Median progression-free survival (PFS) time was 7.0 months and the 1-year PFS rate was 16.2%. Six patients (22.2%) were successfully converted to resection. Compared with primary gallbladder lesions, it appeared more difficult for patients with hepatic metastasis to achieve remission (ORR: 40.7% vs. 77.8%; P=0.012), but its response appeared to be closely related to the prognosis [median OS: 16.0 months in the complete response (CR) or partial response (PR) group vs. 11.0 months in the stable disease (SD) or progressive disease (PD) group, P=0.070; median PFS: 12.0 months in the CR or PR group vs. 6.5 months in the SD or PD group, P<0.001]. Preoperative CA19-9 of >1,900 U/mL and >5 cm metastatic lesions were associated with an unsatisfactory response, whereas a significant decrease of 18F-fluorodeoxyglucose (18F-FDG) uptake may be a marker of tumor remission. The combination of HAIC, a PD-1 inhibitor, and bevacizumab shows potential for advanced GBC with hepatic oligometastasis. The therapeutic response of hepatic metastasis had a greater influence on prognosis than that of primary gallbladder lesions.

New Developments in the Ultrasonography Diagnosis of Gallbladder Diseases

Gallbladder diseases are very common, and their diagnosis is based on clinical–laboratory evaluation and imaging techniques. Considering the different imaging diagnostic tools, ultrasound (US) has the advantage of high accuracy combined with easy availability. Therefore, when a gallbladder disease is suspected, US can readily assist the clinician in the medical office or the emergency department. The high performance of US in the diagnosis of gallbladder diseases is mainly related to its anatomic location. The most frequent gallbladder pathological condition is gallstones disease, easily diagnosed via US examination. Acute cholecystitis (AC), a possible complication of gallstone disease, can be readily recognized due to its specific sonographic features. Additionally, a number of benign, borderline or malignant gallbladder lesions may be detected via US evaluation. The combined use of standard B-mode US and additional sonographic techniques, such as contrast-enhanced ultrasonography (CEUS), may provide a more detailed study of gallbladder lesions. Multiparametric US (combination of multiple sonographic tools) can improve the diagnostic yield during gallbladder examination.

Reply to Fujimoto, T. Comment on "Okaniwa, S. How Can We Manage Gallbladder Lesions by Transabdominal Ultrasound? Diagnostics 2021, 11, 784".

Thank you for your interesting comments [...].

How Can We Identify T1 or Shallow T2 Gallbladder Carcinoma Using Ultrasound? Comment on Okaniwa, S. How Can We Manage Gallbladder Lesions by Transabdominal Ultrasound? Diagnostics 2021, 11, 784.

I am keenly interested in ultrasound diagnosis of the invasion depth of gallbladder carcinoma (GBC) [...].

A Retrospective Single Centre Study on Histopathological Analysis of Cholecystectomy Specimens in a Pakistani Tertiary Care Centre. Is the Spectrum Changing?

Objective: To study the histopathological spectrum of gallbladder diseases and compare the occurrence of gallbladder carcinoma in relation to age, gender and weight of the patient. Methodology: This Cross-sectional study, retrospective study was conducted at Histopathology department of HBS General Hospital and Pakistan Institute of Medical Sciences (PIMS). Study was conducted over a period of 6 months from October 2021 to March 2022. Cholecystectomy specimens from either gender irrespective of their age received at the Histopathology Department of HBS General Hospital and Pakistan Institute of Medical Sciences (PIMS), over a period of 6 months were included in the study. The specimens were fixed in 10% formalin for 24 to 48 hours before sectioning. Then every specimen was macroscopically evaluated followed by cutting of the tissue into three representative sections, one each from the fundus, body and neck of the gallbladder along with the lymph nodes if provided. Hematoxylin &amp; eosin staining was done &amp; specimen. The clinical data from pathology reports and slides were retrieved from the archives and were microscopically examined by the histopathologists and the results were recorded. Results: Mean age of the patients was 54.58 ±18.04 years. Females were more than the male patients. There were 315 (77.4%) female patients as compared to 92 (22.6%) male patients. The mean weight of the patients was 60.18 ±5.11 kg. The most common finding was chronic cholecystitis in 303 out of 407 total cases (85%) followed by acute cholecystitis in 27 cases (9.8%). There were 16 cases (3.9%) of incidental carcinoma and three cases (0.7%) of dysplasia. Conclusion: A spectrum of histopathological diagnosis is observed in cholecystectomy specimen. The inflammatory gallbladder lesions are the most common pathology and the commonest diagnosis is chronic cholecystitis but the doctors cannot rely on the clinical or radiological diagnosis of gallbladder diseases. Histopathological analysis of all gallbladder specimens is necessary for the detection of carcinoma as the frequency of gallbladder cancer appears to be on the rise in our population which is significantly more common in females.

P53 Expression in Gallbladder Lesions: A Cross-sectional Study from a Tertiary Care Centre in Northern India

Introduction: Gallbladder lesions comprise inflammatory, benign, pre-malignant, and malignant lesions. The progression of benign lesions into malignant ones involves a complex process. The p53 gene is commonly disrupted in carcinogenesis. Malignant lesions may exhibit p53 overexpression compared to benign and inflammatory lesions. Aim: To investigate the distribution of gallbladder lesions and the expression of the p53 nuclear protein in these lesions. Materials and Methods: A cross-sectional study was conducted at the Department of Pathology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, from June 2020 to December 2022. A total of 249 specimens of gallbladder lesions, including congenital, inflammatory, benign, pre-malignant, and malignant lesions, were included. All samples underwent Haematoxylin &amp; Eosin(H&amp;E) staining and Immunohistochemistry (IHC) with p53 antibody using the peroxidase-antiperoxidase method. The association of P53 expression with histopathological diagnosis was analysed using Fisher’s Exact test. The final analysis was performed using Statistical Package for Social Sciences (SPSS) software, version 25.0. A p-value &lt;0.05 was considered statistically significant. Results: Out of 249 specimens, there were 217 (87.14%) inflammatory lesions, 9 (3.6%) benign lesions, 2 (0.8%) premalignant lesions, and 21 (9.26%) malignant lesions. The main inflammatory lesions were Chronic Cholecystitis (CC) with 132 cases (60.83%) and CC with cholesterosis with 36 cases (16.59%). The most common pre-malignant lesion was choledochal cyst with 3 cases (3.33%). Benign tumours (leiomyoma) were present in 2 (0.8%) patients. Among the 21 (8.46%) malignant tumours, 4 (19.05%) were moderately differentiated adenocarcinoma, 13 (61.9%) were poorly differentiated adenocarcinoma, and 4 (19.05%) were welldifferentiated adenocarcinoma. P53 overexpression was significantly higher in patients with malignant tumours (9 cases, 42.86%) compared to inflammatory lesions (26 cases, 11.98%), benign lesions (0 cases, 0%), and pre-malignant lesions (0 cases, 0%) (p=0.003). Conclusion: Gallbladder lesions exhibit a wide range of histopathological presentations. Inflammatory lesions are the most common, followed by pre-malignant and malignant lesions. P53 can serve as a novel marker for differentiating inflammatory lesions from malignant lesions in the gallbladder.

P53 Expression in Gallbladder Lesions: A Cross-sectional Study from a Tertiary Care Centre in Northern India

Introduction: Gallbladder lesions comprise inflammatory, benign, pre-malignant, and malignant lesions. The progression of benign lesions into malignant ones involves a complex process. The p53 gene is commonly disrupted in carcinogenesis. Malignant lesions may exhibit p53 overexpression compared to benign and inflammatory lesions. Aim: To investigate the distribution of gallbladder lesions and the expression of the p53 nuclear protein in these lesions. Materials and Methods: A cross-sectional study was conducted at the Department of Pathology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, from June 2020 to December 2022. A total of 249 specimens of gallbladder lesions, including congenital, inflammatory, benign, pre-malignant, and malignant lesions, were included. All samples underwent Haematoxylin &amp; Eosin(H&amp;E) staining and Immunohistochemistry (IHC) with p53 antibody using the peroxidase-antiperoxidase method. The association of P53 expression with histopathological diagnosis was analysed using Fisher’s Exact test. The final analysis was performed using Statistical Package for Social Sciences (SPSS) software, version 25.0. A p-value &lt;0.05 was considered statistically significant. Results: Out of 249 specimens, there were 217 (87.14%) inflammatory lesions, 9 (3.6%) benign lesions, 2 (0.8%) premalignant lesions, and 21 (9.26%) malignant lesions. The main inflammatory lesions were Chronic Cholecystitis (CC) with 132 cases (60.83%) and CC with cholesterosis with 36 cases (16.59%). The most common pre-malignant lesion was choledochal cyst with 3 cases (3.33%). Benign tumours (leiomyoma) were present in 2 (0.8%) patients. Among the 21 (8.46%) malignant tumours, 4 (19.05%) were moderately differentiated adenocarcinoma, 13 (61.9%) were poorly differentiated adenocarcinoma, and 4 (19.05%) were well-differentiated adenocarcinoma. P53 overexpression was significantly higher in patients with malignant tumours (9 cases, 42.86%) compared to inflammatory lesions (26 cases, 11.98%), benign lesions (0 cases, 0%), and pre-malignant lesions (0 cases, 0%) (p=0.003). Conclusion: Gallbladder lesions exhibit a wide range of histopathological presentations. Inflammatory lesions are the most common, followed by pre-malignant and malignant lesions. P53 can serve as a novel marker for differentiating inflammatory lesions from malignant lesions in the gallbladder.

68Ga-DOTA.SA.FAPi as a Versatile Diagnostic Probe for Various Epithelial Malignancies: A Head-to-Head Comparison with 18F-FDG

IntroductionFibroblast Activation Protein (FAP) expressing cancer associated fibroblasts have been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared with the standard-of-care 18F-FDG. MethodsTwenty-five patients enrolled in this prospective study underwent 18F-FDG and 68Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest (ROI’s) on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using standardized uptake values corrected for lean body mass (SUL), SUVmax, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for 18F-FDG) and total lesion FAP expression (TLF for 68Ga-SA.FAPi). ResultsTwenty-five patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of 68Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, 68Ga-SA.FAPi exhibited significantly higher SUVmax (10.3 vs 8.8, p-0.019), SULpeak (6.8 vs 4.9, p-0.000) and SULavg (5.4 vs 4.1, p-0.019) in comparison to 18F-FDG whereas TBR was comparable for both the tracers [TBRLiver: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBRBloodpool: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcatogorical analysis, 68Ga-SA.FAPi demonstrated higher SUVmax, SULpeak and SULavg values for primary disease (SUVmax: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SULpeak: 8.2 (11.2- 6.8) vs 6.3 (8.5-4.4), p-0.037; SULavg: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p- 0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest 68Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher 68Ga-SA.FAPi avidity. Moreover, 68Ga-SA.FAPi identified five additional lung lesions which were missed by 18F-FDG in one case of ACC. Conclusion68Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to 18F-FDG.