Outcomes and predictors of progression in progressive pulmonary fibrosis.

BACKGROUND: Progressive pulmonary fibrosis (PPF) is a general term for a class of interstitial lung diseases (ILDs) characterized by a progressive fibrosing (PF) phenotype. Patients with PPF have decreased lung function, exercise ability, and quality of life. The purpose of this study was to investigate the clinical characteristics, potential associated factors for disease progression, and survival outcomes of patients in the PPF population. METHODS: This study retrospectively reviewed the data of patients diagnosed with ILD between January 2011 and December 2022 at The First Affiliated Hospital of Ningbo University. A PF phenotype was defined based on the criteria that were used in the PPF clinical practice guidelines, which led to the identification of 92 patients with a PF phenotype among the 177 patients with fibrotic ILD. Baseline clinical information and laboratory parameters were collected and analysed in our cohort. RESULTS: Patients in the PPF group had higher tumour marker levels and lower pulmonary function test results at baseline than did those in the non-PPF group. According to the multivariate logistic regression analysis, age >65 years (OR 2.71, 95% CI 1.26-5.89; p = 0.011), LDH >245 U/L (OR 3.07, 95% CI 1.39-6.78; p = 0.006), CA-153 > 35 U/mL (OR 3.16, 95% CI 1.25-7.97; p = 0.015), FVC <60% predicted (OR 4.82, 95% CI 1.60-14.51; p = 0.005), DLCO <50% predicted (OR 3.21, 95% CI 1.43-7.21; p = 0.005), and the UIP-like pattern on chest HRCT (OR 3.65, 95% CI 1.33-10.07; p = 0.012) were potentially associated with the progression of fibrotic interstitial lung diseases (f-ILDs) to PPF. Furthermore, the PPF group had a poorer survival rate than the non-PPF group (p = 0.0045). According to the multivariate Cox regression analysis, an SPAP ≥ 37 mmHg (HR 2.33, 95% CI 1.09-5.00; p = 0.030) and acute exacerbation (HR 2.88, 95% CI 1.26-6.59; p = 0.012) were identified as significant prognostic factors for mortality in patients with PPFs. CONCLUSIONS: Patients who were older, had high CA-153 and LDH levels, had poor pulmonary function test results, or had a UIP-like pattern on chest HRCT were more likely to have indications for the progression of f-ILD to PPF. Increased SPAP and AE are independent risk factors for the prognosis of PPF patients, so additional attention should be given to such patients.

Tenuazonic acid-induced mycotoxicosis in an immunosuppressed mouse model and its prophylaxis with cinnamaldehyde.

Patients with impaired immune systems are particularly vulnerable to infections. With the increasing number of immunocompromised patients, it becomes necessary to design studies that evaluate the effects of toxic contaminants that are a part of our daily lives. Simultaneously, the management of these toxic components also becomes essential. Therefore, the present study evaluated the possible protective role of cinnamaldehyde (Cin) against tenuazonic acid-induced mycotoxicosis in the immunosuppressed murine model. Tenuazonic acid (TeA), a toxin usually produced by Alternaria species, is a common contaminant in tomato and tomato-based products. Evaluating the potential toxicity of a hazardous chemical necessitates the use of in vitro, in vivo, and in silico methods. Here, the immunomodulatory effect of TeA was assessed in vitro using mouse splenocytes. In silico docking was carried out for the tumour markers of eight organs and TeA. The haematological, histopathological, and biochemical aspects were analysed in vivo. The sub-chronic intoxication of mice with TeA showed elevated malondialdehyde, reduced catalase, and superoxide dismutase production, along with abnormal levels of aspartate aminotransferase and alanine transaminase. The treatment with Cin prevented TeA-induced alterations of antioxidant defense enzyme activities and significantly forbade TeA-induced organ damage, showing therapeutic effects and toxicity reduction in TeA-induced mycotoxicosis.

Challenging diagnoses in a case report: Ovarian fibrothecoma with elevated CA125 levels mimicking malignancy.

INTRODUCTION AND IMPORTANCE: Ovarian fibromas are benign tumours arising from the connective tissue of the ovarian cortex, classified into three pathological subtypes: fibroma, thecoma, and fibrothecoma. Their diagnosis is complicated by their solid nature and potential association with ascites and pleural effusion, resembling Meigs syndrome. Elevated serum CA125 levels can further complicate differentiation from malignant ovarian epithelial tumours. CASE PRESENTATION: A 37-year-old female from a rural area presented with a distended abdomen and weight loss lasting 2 months. Clinical examinations revealed a solid pelvic mass and diagnostic tests showed significantly elevated CA125 levels. Imaging suggested a large ovarian mass and surgical intervention confirmed a fibrothecoma of the left ovary. The postoperative course was uneventful, with subsequent resolution of ascites and pleurisy. CLINICAL DISCUSSION: The diagnosis of ovarian fibromas/fibrothecomas poses challenges due to their asymptomatic nature, solid appearance, and occasional association with the Meigs syndrome. Elevated CA125 levels can mislead the diagnosis of epithelial ovarian carcinoma. The case underscores the importance of considering ovarian fibromas/fibrothecomas in the differential diagnosis of ovarian tumours with elevated CA125 levels, especially in women of reproductive age. The benign nature of these tumours necessitates a conservative surgical approach, emphasizing the importance of intraoperative frozen section analysis. CONCLUSION: Ovarian fibrothecomas associated with elevated serum CA125 levels are rare. Their presentation can mimic malignant ovarian neoplasms, leading to potential diagnostic confusion. Surgical removal remains the treatment of choice, with a favorable prognosis post-surgery.

Prevalence of CEA, CA 125, and CA 15-3 serum tumour markers in different regions of Saudi Arabia.

OBJECTIVES: To study the prevalence of tumor marker (TM) carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), and cancer antigen 15-3 (CA 15-3) levels in the Saudi population, based on gender, age, and demographic region, and whether the patients were referred by a hospital or self-referred. METHODS: Retrospective analysis was carried out on 7,019 samples gathered from the Western, Northern, Central, Southern, and Eastern regions of Saudi Arabia between 2021-2022. The TMs were categorized into normal and abnormal levels, according to the reference ranges. Statistical analysis was carried out to assess the relations between variants (age groups, gender, and demographic regions) using the Chi-square test, and their correlations were assessed using Spearman's test. RESULTS: Among all patients, CEA, CA 125, and CA 15-3 levels were found to be significantly correlated with age (p=0.0001). The CEA and CA 15-3 levels increased in both males and females with age. The CA 125 was shown to have an abnormally increased level in males with age. CONCLUSION: Increased levels of CEA, CA 125, and CA 15-3 TMs in the study population were significantly correlated with age. The CEA and CA 15-3 levels were within the normal range, while CA 125 levels were above the normal range in the older male population. These results suggest that the utilization of such TMs is age dependent and would have validity if applied with other parameters.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

Diagnosis of Canine Tumours and the Value of Combined Detection of VEGF, P53, SF and NLRP3 for the Early Diagnosis of Canine Mammary Carcinoma.

The average life of a dog is generally maintained at ten to fifteen years, and tumours are the predominant reason that leads to the death of dogs, especially canine mammary carcinoma. Therefore, early diagnosis of tumours is very important. In this study, tumor size, morphology, and texture could be seen through general clinical examination, tumor metastasis could be seen through imaging examination, inflammatory reactions could be seen through hematological examination, and abnormal cell morphology could be seen through cytological and histopathological examination. In the 269 malignant cases and 179 benign cases, we randomly selected 30 cases each, and an additional 30 healthy dogs were selected for the experiment (healthy dogs: dogs in good physical condition without any tumor or other diseases). We used RT-qPCR and ELISA to determine the relative expression of vascular endothelial growth factor (VEGF), tumor protein P53 (P53), serum ferritin (SF), and NOD-like receptor protein 3 (NLRP3) in 30 healthy dogs, 30 dogs with benign mammary tumours, and 30 dogs with malignant mammary tumours. In the results, the same expression trend was obtained both in serum and tissues, and the expression of the four markers was the highest in malignant mammary tumours, with highly significant differences compared with the benign and healthy/paracancerous groups. By plotting the ROC curves, it was found that the results of combined tests were better than a single test and the combination of the four markers was the best for the early diagnosis. In conclusion, this can assist the clinical early diagnosis to a certain extent, and also provides some references and assistance for the development of tumor detection kits in clinical practice.

Targeting tumour markers in ovarian cancer treatment.

Ovarian cancers (OC) are the most common, lethal, and stage-dependent cancers at the global level, specifically in female patients. Targeted therapies involve the administration of drugs that specifically target the alterations in tumour cells responsible for their growth, proliferation, and metastasis, with the aim of treating particular patients. Presently, within the realm of gynaecological malignancies, specifically in breast and OCs, there exist various prospective therapeutic targets encompassing tumour-intrinsic signalling pathways, angiogenesis, homologous-recombination deficit, hormone receptors, and immunologic components. Breast cancers are often detected in advanced stages, primarily due to the lack of a reliable screening method. However, various tumour markers have been extensively researched and employed to evaluate the condition, progression, and effectiveness of medication treatments for this ailment. The emergence of recent technological advancements in the domains of bioinformatics, genomics, proteomics, and metabolomics has facilitated the exploration and identification of hitherto unknown biomarkers. The primary objective of this comprehensive review is to meticulously investigate and analyze both established and emerging methodologies employed in the identification of tumour markers associated with OC.

Challenging Case of Anaplastic Thyroid Cancer With Unusual Clinical and Histological Features: A Diagnostic Dilemma With Undifferentiated Pleomorphic Sarcoma.

Thyroid cancer is a common malignancy worldwide, and its incidence is increasing rapidly, especially in women. In the majority of cases, it presents solely with a palpable neck swelling. Less commonly, the disease manifests with symptoms of advanced stages, such as superior vena cava (SVC) obstruction and indications of recurrent laryngeal nerve invasion. Anaplastic thyroid cancer is a rare variant of thyroid cancer and is considered to have one of the poorest prognoses, and its diagnosis and treatment are challenging. On the other hand, undifferentiated pleomorphic sarcoma is a differential diagnosis with many clinical and histological similarities, which can only be confirmed through immunohistochemical studies. We herein report a challenging case of a 69-year-old female patient who presented with obstructive symptoms, diagnosed with anaplastic thyroid cancer exhibiting unusual clinical and histological features.

Serum Raman spectroscopy: Evaluation of tumour load variations in experimental carcinogenesis.

Several serum Raman spectroscopy (RS) studies have demonstrated its potential as an oral cancer screening tool. This study investigates influence of low tumour load (LTL) and high tumour load (HTL) on serum RS using hamster buccal pouch model of experimental oral carcinogenesis. Sera of untreated control, LTL, and HTL groups at week intervals during malignant transformation were employed. Serum Raman spectra were subjected to multivariate analyses-principal component analysis, principal component-based linear discriminant analysis (for stratification of study groups), and multivariate curve resolution-alternating least squares (MCR-ALS) (to comprehend biomolecular differences). Multivariate analysis revealed misclassifications between LTL and HTL at all week intervals. MCR-ALS components showed statistically significant abundances between control versus LTL and control versus HTL, but could not discern LTL and HTL. MCR-ALS components exhibited spectral mixtures of proteins, lipids, heme and nucleic acids. Thus, these findings support use of serum RS as a screening tool as varying tumour load is not a confounding factor influencing the technique.

Elevated serum CA199 levels in patients suffering type 2 diabetes vs. various types of cancer.

AIMS: Carbohydrate antigen 199 (CA199) is a standard tumor marker, and recent studies have found elevated in CA199 levels in patients with diabetes. However, there is no systematic measurement and comparison of serum CA199 levels in patients with diabetes and cancer. Here, a detailed description of the changes in serum CA199 levels in patients with type 2 diabetes and various cancers was explored. METHODS: A total of 5,641 participants were screened for clinical laboratory test results of serum CA199 levels over the past three years (2020-2023). This study included 2,464 healthy controls, 688 patients with type 2 diabetes, and 2,489 patients with 16 different types of cancer. Each type of cancer had more than 30 independent serum CA199 level test results. The serum CA199 levels were compared between cancer groups, type 2 diabetes patients, and healthy controls. Additionally, the CA199 levels of cancer patients were compared with those of patients with type 2 diabetes. RESULTS: The serum CA199 levels of esophagus cancer, lung cancer, pancreatic cancer, ovarian cancer, breast cancer, rectum cancer, prostate cancer, bladder cancer, liver cancer, gastric cancer, cervical cancer, colon cancer, lymphoma, thyroid cancer, intracranial tumors, and nasopharyngeal laryngeal cancer were found to be elevated compared to healthy controls (P < 0.01). In addition, the serum CA199 levels of patients with type 2 diabetes were also significantly elevated compared to healthy controls (P < 0.01). Moreover, the degree of elevation in serum CA199 levels in patients with type 2 diabetes was not significantly different from that observed in some types of cancer, such as esophagus cancer (P = 0.163), breast cancer (P = 0.927), prostate cancer (P = 1.000), bladder cancer (P = 0.406), Lymphoma (P = 0.975), thyroid cancer (P = 1.000), intracranial tumors (P = 0.161), nasopharyngeal and laryngeal cancer (P = 1.000). CONCLUSIONS: Serum CA199 levels also increase in type 2 diabetes, and the magnitude of the increase is similar to that seen in some cancers.

Diagnosis and treatment of hepatic cysts. Usefulness of intracystic tumor markers (CEA and CA 19.9.).

INTRODUCTION: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers. METHODS: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9. RESULTS: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 µg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively. CONCLUSION: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia.

Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed. DESIGN: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites. RESULTS: Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92). CONCLUSION: A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.

Evaluation of Expression of WNT1 and PTCH Genes in Peripheral Blood of Patients with Odontogenic Cysts and Tumours of the Jaws by Quantitative RT-PCR: A Pilot Study.

Introduction: Odontogenic lesions of the maxillofacial region constitute a complex group of lesions with diverse histopathologic types and clinical behaviour. Early diagnosis is important to minimize the need for radical surgery and to improve quality of life of the patients. Tumour markers play an essential role in the molecular level understanding of Odontogenic lesions and also used for early diagnosis and target therapies which improves the quality of life of the patients. Patched, a tumour suppressor gene encodes the transmembrane protein PTCH and is a receptor for the morphogen Sonic Hedgehog. It is evident that PTCH gene mutations occur in odontogenic keratocysts and the Hedgehog signalling pathway has an important role during tooth formation. WNT 1 is a key signal molecule that controls cell growth and proliferation. WNT pathway abnormalities are reported to induce tumour occurrence. Hence, my study was to determine the presence of WNT1 and PTCH in peripheral blood of patients with Odontogenic lesions using quantitative RT-PCR. Materials and Methods: In this cross-sectional study, two groups were included: Group 1-blood samples from 8 individuals with odontogenic cysts and tumours, and Group 2-blood samples of 8 individuals without Odontogenic lesions. 2 ml of blood sample was collected from radial veins into PAX gene tubes containing RNA stabilizing agent and stored at a temperature of 2 to 4 degrees and transported to Enable Biolabs India Pvt Ltd., Chennai. PAX gene tubes were subjected to centrifugation at 8000 rpm to separate plasma fraction. Reverse transcription of mRNA was performed using miScript II RT Kit (Cat#218161, Qiagen, Germany) to synthesize cDNA. GAPDH house-keeping gene used as control. Results: The study group had 3 males and 5 females (n = 8) with a mean age group of 32.6 years and the control group had 2 males and 6 females (n = 8) with mean age of 35.2 years. Group I (study group) showed 37.5% positive expression of WNT1 gene with a p value of 0.055 (p > 0.05) and 50% positive expression of PTCH with a p value of 0.021 (p < 0.05) (Figs. 3 and 4) which was statistically significant when compared with control group. Group II (control group) showed 100% negative expression for WNT1 and PTCH genes. Conclusion: WNT1 and PTCH genes were expressed in peripheral blood of patients with odontogenic lesions. WNT1 and PTCH genes may be potential predictors in individuals who would develop odontogenic lesions. Further studies on expression of WNT1 and PTCH genes with larger number of samples might give a future scope for target therapy in odontogenic lesions.

Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes.

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes. Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated. Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types. Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

The Importance of Basal Cell Carcinoma Risk Stratification and Potential Future Pathways.

BACKGROUND: Basal cell carcinoma (BCC) is the most common human cancer. Although there are surgical and topical treatments available, surgery remains the mainstay of treatment, leading to higher costs. What is needed is an accurate risk assessment of BCC so that treatments can be planned in a patient-centered manner. OBJECTIVE: In this study, we will review the literature about guidelines for the management of BCC and analyze the potential indicators of high-risk BCC. Using this risk assessment approach, we will propose pathways that will be able to optimize treatments more efficiently. METHODS: This paper presents a perspective from a skin cancer expert and clinic involved in the treatment of both simple and complex cases of BCC. It addresses the key challenges associated with accurate risk stratification prior to any treatment or procedure. Different immunohistochemical and angiogenic markers for high-risk BCC were reviewed in this study. RESULTS: The expression of interleukin-6, vascular endothelial growth factor, and mast cells within BCC correlates with its aggressiveness. Other immunohistochemical markers, such as Cyclin D1 and Bcl-2, also play a significant role-Cyclin D1 is higher in the aggressive BCC, while Bcl-2 is lower in the aggressive BCC, compared to the nonaggressive variants. CONCLUSIONS: Based on our research, we will conclude that using immunohistochemical and angiogenic markers for risk assessment and stratification of BCC can help optimize treatment, ensuring that surgical procedures are used only when necessary.

An unusual presentation of a primary lung adenocarcinoma: A case report.

INTRODUCTION AND IMPORTANCE: Lung cancer is one of the most common malignancies worldwide and common sites of metastasis are to brain, liver, adrenal glands, and bones [1]. Metastasis to the gastrointestinal (GI) tract is extremely rare (<1%) and the most common site is the small intestine [5]. CASE PRESENTATION: A 60-year-old female referred for intermittent colicky abdominal pain and diarrhoea, with cross-sectional imaging showing a distal small bowel mass with lymphadenopathy. Malignancy workup revealed an additional mediastinal mass and raised tumour marker carcinoembryonic antigen (CEA). Bronchoscopy confirmed primary lung adenocarcinoma of the mediastinal mass. Given the raised CEA, evolving obstructive symptoms, and concerns for synchronous lung and gastrointestinal primaries, the patient proceeded to have a small bowel resection leading to the diagnosis of a GI lung metastasis. CLINICAL DISCUSSION: If Symptomatic, suggested treatment of lung metastasis to the GI tract is surgical resection. Current evidence suggests that in isolated GI metastases, resection may have a therapeutic benefit and an association with overall survival rate. CONCLUSION: In patients with symptomatic or isolated GI lung metastasis, surgical resection should be considered for treatment and management of metastatic disease. The role of tumour marker CEA in primary lung adenocarcinoma is unclear.

Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes.

BACKGROUND: Hepatocellular carcinoma (HCC) is difficult to diagnose with poor therapeutic effect, high recurrence rate and has a low survival rate. The survival of patients with HCC is closely related to the stage of diagnosis. At present, no specific serological indicator or method to predict HCC, early diagnosis of HCC remains a challenge, especially in China, where the situation is more severe. AIM: To identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators. METHODS: The clinical data of patients in the Affiliated Hospital of North Sichuan Medical College from 2016 to 2020 were collected, using a retrospective study method. The results of needle biopsy or surgical pathology were used as the grouping criteria for the experimental group and the control group in this study. Based on the time of admission, the cases were divided into training cohort (n = 1739) and validation cohort (n = 467). Using HCC as a dependent variable, the research indicators were incorporated into logistic univariate and multivariate analysis. An HCC risk prediction model, which was called NSMC-HCC model, was then established in training cohort and verified in validation cohort. RESULTS: Logistic univariate analysis showed that, gender, age, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II, gamma-glutamyl transferase, aspartate aminotransferase and hepatitis B surface antigen were risk factors for HCC, alanine aminotransferase, total bilirubin and total bile acid were protective factors for HCC. When the cut-off value of the NSMC-HCC model joint prediction was 0.22, the area under receiver operating characteristic curve (AUC) of NSMC-HCC model in HCC diagnosis was 0.960, with sensitivity 94.40% and specificity 95.35% in training cohort, and AUC was 0.966, with sensitivity 90.00% and specificity 94.20% in validation cohort. In early-stage HCC diagnosis, the AUC of NSMC-HCC model was 0.946, with sensitivity 85.93% and specificity 93.62% in training cohort, and AUC was 0.947, with sensitivity 89.10% and specificity 98.49% in validation cohort. CONCLUSION: The newly NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.

Paediatric reference ranges for plasma chromogranin A.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare diseases with varied aggressiveness originating from endocrine cells belonging to the diffuse endocrine system and most often produce and secrete chromogranin A (CgA). CgA in plasma is therefore used to screen, diagnose, and monitor for NENs in both adults and children with sporadic or familial NENs. METHODS: Plasma CgA was measured using the Brahms Kryptor assay in 268 healthy children/adolescents; 85 children were tested as part of a familial cancer screening program and 183 additional children younger than 20 years of age underwent screening for allergies. Repeated measurements (month - years) was used to calculate the intra-individual variation. The dataset was analysed in R using the referenceInterval package. RESULTS: The plasma CgA concentration decreased with age and was 32-118 µg/L for children aged 0-3 years, 18-85 µg/L for children aged 4-13 years, and 6-79 µg/L for adolescents aged 14-19 years. Earlier reported CgA reference intervals for adults have upper limits from 88 to 102 µg/L while no lower limits have been reported. The median for the three groups were 78, 51, and 39 µg/L, respectively. The median intra-individual variation was 14% (25%-centile 9.4%/75%-centile 21%). CONCLUSIONS: The reference interval will be useful when screening, diagnosing, and monitoring children for NENs respecting the limitations plasma CgA has.

A Case of Inflammatory Pseudotumour Masquerading as Hepatocellular Carcinoma.

Inflammatory pseudotumors (IPTs) of the liver can mimic malignant lesions. As the name implies, they are usually associated with an inflammatory process and usually regress with the treatment of the underlying pathology. We report a case of a 67-year-old female who presented with right upper quadrant pain, deranged liver enzymes, elevated tumor markers [alpha-fetoprotein (AFP) and CA 19-9], and a large liver mass on imaging, suspected to be hepatocellular carcinoma (HCC). She was eventually diagnosed with IPT complicating the liver inflammation due to autoimmune hepatitis (AIH). She responded well to treatment with steroids and immunosuppressive therapy.

Carbohydrate sulfotransferases: a review of emerging diagnostic and prognostic applications.

Carbohydrate sulfotransferases (CHST) catalyse the biosynthesis of proteoglycans that enable physical interactions and signalling between different neighbouring cells in physiological and pathological states. The study aim was to provide an overview of emerging diagnostic and prognostic applications of CHST. PubMed database search was conducted using the keywords "carbohydrate sulfotransferase" together with appropriate inclusion and exclusion criteria, whereby 41 publications were selected. Additionally, 40 records on CHST genetic and biochemical properties were hand-picked from UniProt, GeneCards, InterPro, and neXtProt databases. Carbohydrate sulfotransferases have been applied mainly in diagnostics of connective tissue disorders, cancer and inflammations. The lack of CHST activity was found in congenital connective tissue disorders while CHST overexpression was detected in different malignancies. Mutations of CHST3 gene cause skeletal dysplasia, chondrodysplasia, and autosomal recessive multiple joint dislocations while increased tissue expression of CHST11, CHST12 and CHST15 is an unfavourable prognostic factor in ovarian cancer, glioblastoma and pancreatic cancer, respectively. Recently, CHST11 and CHST15 overexpression in the vascular smooth muscle cells was linked to the severe lung pathology in COVID-19 patients. Promising CHST diagnostic and prognostic applications have been described but larger clinical studies and robust analytical procedures are required for the more reliable diagnostic performance estimations.