Vibrational spectroscopy-are we close to finding a solution for early pancreatic cancer diagnosis?

Pancreatic cancer(PC)is an aggressive and lethal neoplasm,ranking seventh in the world for cancer deaths,with an overall 5-year survival rate of below 10%.The knowledge about PC pathogenesis is rapidly expanding.New aspects of tumor biology,including its molecular and morphological heterogeneity,have been reported to explain the complicated“cross-talk”that occurs between the cancer cells and the tumor stroma or the nature of pancreatic ductal adenocarcinoma-associated neural remodeling.Nevertheless,currently,there are no specific and sensitive diagnosis options for PC.Vibrational spectroscopy(VS)shows a promising role in the development of early diagnosis technology.In this review,we summarize recent reports about improvements in spectroscopic methodologies,briefly explain and highlight the drawbacks of each of them,and discuss available solutions.The important aspects of spectroscopic data evaluation with multivariate analysis and a convolutional neural network methodology are depicted.We conclude by presenting a study design for systemic verification of the VS-based methods in the diagnosis of PC.

Novel Computer-Aided Diagnosis System for the Early Detection of Alzheimer’s Disease

Aging is a natural process that leads to debility,disease,and dependency.Alzheimer’s disease(AD)causes degeneration of the brain cells leading to cognitive decline and memory loss,as well as dependence on others to fulfill basic daily needs.AD is the major cause of dementia.Computer-aided diagnosis(CADx)tools aid medical practitioners in accurately identifying diseases such as AD in patients.This study aimed to develop a CADx tool for the early detection of AD using the Intelligent Water Drop(IWD)algorithm and the Random Forest(RF)classifier.The IWD algorithm an efficient feature selection method,was used to identify the most deterministic features of AD in the dataset.RF is an ensemble method that leverages multiple weak learners to classify a patient’s disease as either demented(DN)or cognitively normal(CN).The proposed tool also classifies patients as mild cognitive impairment(MCI)or CN.The dataset on which the performance of the proposed CADx was evaluated was sourced from the Alzheimer’s Disease Neuroimaging Initiative(ADNI).The RF ensemble method achieves 100%accuracy in identifying DN patients from CN patients.The classification accuracy for classifying patients as MCI or CN is 92%.This study emphasizes the significance of pre-processing prior to classification to improve the classification results of the proposed CADx tool.

A molecular probe carrying anti-tropomyosin 4 for early diagnosis of cerebral ischemia/reperfusion injury

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.

Non-Invasive Approach to Early Diagnosis of the Formation of Oncological Neoplasms

The currently developed instrumental approaches for detecting pathological changes in the body have a number of disadvantages. The most important of them is that the equipment is sensitive to the detection of diseases only from a certain threshold level of destructive changes in the body. The present article discusses the possibility of using the new instrumental complex “Bioscope” for early and non-invasive diagnosis of the beginning of the formation of ontological neoplasm’s in the body.

Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.AIM To explore the clinical characteristics of early-stage PBC,identify PBC in the early clinical stage,and promptly treat and monitor PBC.METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People’s Hospital from January 2013 to November 2021 were collected,and the patients were divided into stage I,stage II,stage III,and stage IV according to the pathological stage.The general data,serum biochemistry,immunoglobulins,and autoimmune antibodies of patients in each stage were retrospectively analyzed.RESULTS In early-stage(stages I+II)PBC patients,50.0%of patients had normal alanine aminotransferase(ALT)levels,and 37.5%had normal aspartate aminotransferase(AST)levels.For the remaining patients,the ALT and AST levels were mildly elevated;all of these patients had levels of<3 times the upper limit of normal values.The AST levels were significantly different among the three groups(stages I+II vs stage III vs stage IV,P<0.05).In the early stage,29.2%of patients had normal alkaline phosphatase(ALP)levels.The remaining patients had different degrees of ALP elevation;6.3%had ALP levels>5 times the upper limit of normal value.Moreover,γ-glutamyl transferase(GGT)was more robustly elevated,as 29.2%of patients had GGT levels of>10 times the upper limit of normal value.The ALP values among the three groups were significantly different(P<0.05).In early stage,the jaundice index did not increase significantly,but it gradually increased with disease progression.However,the above indicators were significantly different(P<0.05)between the early-stage group and the stage IV group.With the progression of the disease,the levels of albumin and albumin/globulin ratio tended to decrease,and the difference among the three groups was statistically significant(P<0.05).In early-stage patients,IgM and IgG levels as well as cholesterol levels were mildly elevated,but there were no significant differences among the three groups.Triglyceride levels were normal in the early-stage group,and the differences among the three groups were statistically significant(P<0.05).The early detection rates of anti-mitochondria antibody(AMA)and AMA-M2 were 66.7%and 45.8%,respectively.The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC.When AMA and AMA-M2 were negative,in the early stage,the highest autoantibody was anti-nuclear antibody(ANA)(92.3%),and in all ANA patterns,the highest was ANA centromere(38.5%).CONCLUSION In early-stage PBC patients,ALT and AST levels are normal or mildly elevated,GGT and ALP levels are not elevated in parallel,GGT levels are more robustly elevated,and ALP levels are normal in some patients.When AMA and AMA-M2 are negative,ANA especially ANA centromere positivity suggests the possibility of early PBC.Therefore,in the clinic,significantly elevated GGT levels with or without normal ALP levels and with ANA(particularly ANA centromere)positivity(when AMA and AMA-M2 are negative)may indicate the possibility of early PBC.

Controversies in the diagnosis and management of early gastric cancer

Early diagnosis and treatment is the key to improving the prognosis of gastric cancer. The past decades have wimessed the rapid advances in the diagnosis and management of early gastric cancer （EGC）： endoscopy has played an increasingly important role, whereas laparoscopic techniques have also been introduced for EGC treatment. In China, the proportion of EGC is gradually increasing, and this condition will soon become a hot research topic. In this article, we will elucidate some major controversies in the diagnosis and management of EGC.

Early diagnosis of esophageal cancer:How to put“early detection”into effect?

This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology,focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving“early detection”.The five-year age-standardized net survival for esophageal cancer patients falls short of expectations.Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer.While advancements in endoscopic technology have been significant,there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques.Therefore,it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer,investigate the most cost-effective screening methods suitable for different regions,and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge

Diagnosing early-stage pancreatic cancer(PC)remains a clinical challenge.Hence,studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative.This article aims to un-derscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC,thereby improving its management and prognosis.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

Recent advances in gastric cancer early diagnosis

Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Application of surface-enhanced laser desorption/ionization time-of-flight-based serum proteomic array technique for the early diagnosis of prostate cancer

Aim： To identify the serum biomarkers of prostate cancer （PCa） by protein chip and bioinformatics. Methods： Serum samples from 83 PCa patients and 95 healthy men were taken from a mass screening in Changchun, China. Protein profiling was carried out using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF MS）. The data of spectra were analyzed using two bioinformatics tools. Results： Eighteen serum differential proteins were identified in the PCa group compared with the control group （P 〈 0.01）. There were four proteins at the higher serum level and 14 proteins at the lower serum level in the PCa group. A decision tree classification algorithm that used an eight-protein mass pattern was developed to correctly classify the samples. A sensitivity of 92.0 % and a specificity of 96.7 % for the study group were obtained by comparing the PCa and control groups. Conclusion： We identified new serum biomarkers of PCa. SELDI-TOF MS coupled with a decision tree classification algorithm will provide a highly accurate and innovative approach for the early diagnosis of PCa. （Asian J Androl 2006 Jan; 8： 45-51）

Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer

AIM:To evaluate the diagnostic effectiveness of white light endoscopy,magnifying endoscopy(ME),and magnifying narrow-band imaging endoscopy(ME-NBI) in detecting early gastric cancer(EGC).METHODS:From March 2010 to June 2012,a total of 3616 patients received screening for gastric cancer by magnifying endoscopy. There were 3675 focal gastric lesions detected using conventional high definition white light endoscopy(HD-WLE) in four different referentialhospitals that were recruited for further investigation using ME and ME-NBI. The images obtained from HD-WLE,ME,and ME-NBI were reviewed by four experienced endoscopists to evaluate their diagnostic effectiveness for EGC. The diagnosis of cancerous and non-cancerous lesions was conducted by evaluating the microvascular and microsurface patterns using the VS classification system. The final endoscopic diagnosis of each lesion was determined by consultation when a disagreement occurred. We used histopathological results as the gold standard for the diagnosis of EGC.RESULTS:Among the 3675 lesions found,1508 were validated by pathological findings as chronic gastritis,1279 as chronic gastritis with intestinal metaplasia,631 as low-grade neoplasia,and 257 as EGC. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of HD-WLE for the diagnosis of EGC were 71.2%,99.1%,85.5%,97.9% and 97.1%,respectively. The results of ME for diagnosing EGC were 81.3%,98.8%,83.3%,98.6% and 97.6%,respectively. The results of ME-NBI for the diagnosis of EGC were 87.2%,98.6%,82.1%,99.0% and 97.8%,respectively. The diagnostic sensitivity and accuracy of paired ME and ME-NBI were significantly better than those of HD-WLE(P < 0.05).CONCLUSION:HD-WLE has a relatively high accuracy for diagnosing EGC and is an effective screening tool. Further investigations of ME and ME-NBI are required to achieve superior accuracy.

Challenges to the early diagnosis and treatment of breast cancer in developing countries

This critical review of the literature assembles and compares available data on breast cancer clinical stage, time intervals to care, and access barriers in different countries. It provides evidence that while more than 70% of breast cancer patients in most high-income countries are diagnosed in stages Ⅰ and Ⅱ, only 20%-50% patients in the majority of low- and middleincome countries are diagnosed in these earlier stages. Most studies in the developed world show an association between an advanced clinical stage of breast cancer and delays greater than three months between symptom discovery and treatment start. The evidence assembled in this review shows that the median of this interval is 30-48 d in high-income countries but 3-8 mo in low- and middle-income countries. The longest delays occur between the first medical consultation and the beginning of treatment, known as the provider interval. The little available evidence suggests that access barriers and quality deficiencies in cancer care are determinants of provider delay in low- and middle-income countries. Research on specific access barriers and deficiencies in quality of care for the early diagnosis and treatment of breast cancer is practically non-existentin these countries, where it is the most needed for the design of cost-effective public policies that strengthen health systems to tackle this expensive and deadly disease.

Improved early diagnosis of cystadenocarcinoma of the pancreas

BACKGROUND: Cystadenocarcinoma of the pancreas is insensitive to radiotherapy and chemotherapy, and surgery is at present the definitive treatment. Early and accurate diagnosis of cystadenocarcinoma is crucial for increasing the five-year survival rate and the resectable rate. There is no definitive and effective method of early diagnosis of cystadenocarcinoma of the pancreas in China and other countries. METHODS: We compared endoscopic ultrasonography-guided (EUS-guided) fine needle aspiration biopsy combined with cyst fluid carcinoembryonic antigen (CEA), CA19-9 examination with computed tomography (CT), B-ultrasonography (B-US) and serum CEA and CA19-9, to explore methods of early diagnosis of cystadenocarcinoma of the pancreas. Retrospective analysis was made on the clinical data of 126 cases of benign pancreatic lesion (90 cases) and cystadenocarcinoma (36). RESULTS: The sensitivity of B-US and CT for cystadenocarcinoma was 52.8% and 77.8%, while the specificity was 78.9% and 86.7%, respectively. When measurement of CEA and CA19-9 of cyst fluid was combined with EUS-guided fine needle aspiration biopsy, the sensitivity was 94.4%, higher than that of B-US and CT (P<0.05). The sensitivity of cyst fluid CEA, CA19-9 examinations was considerably higher than that of serum CEA, CA19-9 (P<0.05). Upper gastrointestinal barium meal and endoscopic retrograde cholangiopancreatography (ERCP) had low sensitivity and specificity. CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid CEA, CA19-9 is a credible means for early diagnosis of cystadenocarcinoma of the pancreas. B-US, CT and serum CEA, CA19-9 measurements are in common use, their findings are also very important.

The value of three-dimensional computed tomographic angiography in the early diagnosis and treatment of spontaneous subarachnoid hemorrhage (616 cases report)

Objective To evaluate the clinical value of three dimensional computerized tomography angiography in the diagnosis and treatment of spontaneous subarachnoid hemorrhage. Methods 616 cases were diagnosed as suspected intracranial aneurysms in 3D CTA system. Computed tomographic scans and CTA studies were

Advances in early diagnosis and therapy of pancreatic cancer

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database) RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

GEAR CRACK EARLY DIAGNOSIS USING BISPECTRUM DIAGONAL SLICE

A study of bispectral analysis in gearbox condition monitoring is presented.The theory of bispectrum and quadratic phase coupling (QPC) is first introduced, and then equationsfor computing bispectrum slices are obtained. To meet the needs of online monitoring, a simplifiedmethod of computing bispectrum diagonal slice is adopted. Industrial gearbox vibration signalsmeasured from normal and tooth cracked conditions are analyzed using the above method. Experimentsresults indicate that bispectrum can effectively suppress the additive Gaussian noise andchracterize the QPC phenomenon. It is also shown that the 1-D bispectrum diagonal slice can capturethe non-Gaussian and nonlinear feature of gearbox vibration when crack occurred, hence, this methodcan be employed to gearbox real time monitoring and early diagnosis.

Comparison of plasma microRNA-1 and cardiac troponin T in early diagnosis of patients with acute myocardial infarction

BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.

Diagnosis of boundary in early gastric cancer

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique,which allowsresection of larger superficial tumors in the esophagus,stomach,and colon.Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD,because too much resection can potentially take more time and can induce a higher complication rate,while too little resection can result in a non-curative resection.The boundary diagnosis is often difficult for early gastric cancer,mainly because of the underlying condition of chronic gastritis.Due to recent developments in endoscopy,including magnified endoscopy and narrow band endoscopy,the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.