Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions:A rare case report

BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures

Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists.Despite advances in endoscopic techniques and instruments,it is difficult to differentiate between benign and malignant pathology.A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery,or to inform other types of therapy.Endoscopic retrograde cholangiopancreato-graphy with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate.Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality.In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate histology to facilitate clinical management.

Clinical approach to indeterminate biliary strictures:Clinical presentation,diagnosis,and workup

Despite advances in cross-sectional imaging and endoscopic technology,bile duct strictures remain a challenging clinical entity.It is crucial to make an early determination of benign or malignant nature of biliary strictures.Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis.Conventional imaging and endoscopic techniques,particularly endoscopic retrograde cholangiopancreatography(ERCP)and tissue sampling techniques play a key in establishing a diagnosis.Indeterminate biliary strictures(IDBSs)have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology.In this review,we discuss possible etiologies,clinical presentation,diagnosis,and management of IDBSs.Based on available data and expert opinion,we depict an evidence based diagnostic algorithm for management of IDBSs.Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology,intraductal biopsies,fluorescence in situ hybridization and flow cytometry.We also describe the role of endoscopic ultrasound(EUS)-guided fine needle aspiration and biopsies,cholangioscopy,confocal laser endomicroscopy,and intraductal EUS in management of IDBSs.

Role of artificial intelligence in the characterization of indeterminate pancreatic head mass and its usefulness in preoperative diagnosis

Artificial intelligence(AI)has been used in various fields of day-to-day life and its role in medicine is immense.Understanding of oncology has been improved with the introduction of AI which helps in diagnosis,treatment planning,management,prognosis,and follow-up.It also helps to identify high-risk groups who can be subjected to timely screening for early detection of malignant conditions.It is more important in pancreatic cancer as it is one of the major causes of cancer-related deaths worldwide and there are no specific early features(clinical and radiological)for diagnosis.With improvement in imaging modalities(computed tomography,magnetic resonance imaging,endoscopic ultrasound),most often clinicians were being challenged with lesions that were difficult to diagnose with human competence.AI has been used in various other branches of medicine to differentiate such indeterminate lesions including the thyroid gland,breast,lungs,liver,adrenal gland,kidney,etc.In the case of pancreatic cancer,the role of AI has been explored and is still ongoing.This review article will focus on how AI can be used to diagnose pancreatic cancer early or differentiate it from benign pancreatic lesions,therefore,management can be planned at an earlier stage.

Current endoscopic approach to indeterminate biliary strictures

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

Indeterminate pulmonary nodules in colorectal cancer

AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpatients,40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography(CT)were enrolled.The decision to perform a lung operation was made if the patient met the following criteria:(1)completely resected or resectable primary CRC;(2)completely resectable IPNs;(3)controlled or controllable extrapulmonary metastasis;and(4)adequate general condition and pulmonary function to tolerate pulmonary operation.Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation.RESULTS:A total of 40 cases of lung resection was performed in 29 patients.Five patients underwent repeated lung resection.The final pathology result showed metastasis from the CRC in 30 cases(75%)and benign pathology in 10 cases(25%).The primary tumor site was the rectum in 26/30(86.6%)cases with pulmonary metastasis,but only 3/10(30%)cases in the benign group had a primary rectal cancer(P=0.001).Positron emission tomography(PET)-CT was performed for 22/30(73.4%)patients in the lung metastasis group and for 6/10(60.0%)patients in the benign group.PET-CT revealed hot uptake of18fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups.The group with pulmonary metastasis had a higher incidence of primary rectal cancer(P=0.001),a more advanced tumor stage(P=0.011),and more frequent lymphatic invasion of tumor cells(P=0.005).Six cases with previous liver metastasectomy were present in the lung metastasis group.Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients.CONCLUSION:The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.

Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn's colitis

Patients with indeterminate colitis(IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis(UC) or Crohn's colitis(CC) which is not offered in 15%-30% of inflammatory bowel disease(IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry(MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as beingeither a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis.

Histopathology and the predominantly progressive,indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy

BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.

Indeterminate liver lesions on gadoxetic acid-enhanced magnetic resonance imaging of the liver:Case-based radiologic-pathologic review

Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology.It is necessary to characterise focal liver lesions accurately as not only benign and malignant lesions are managed differently,but also certain benign lesions have differing management.These lesions are increasingly being detected due to rapid growth of use of crosssectional imaging as well as improvement in image quality and new imaging techniques.Contrast enhanced magnetic resonance imaging(MRI)is considered the gold standard technique in characterising focal liver lesions.Addition of gadoxetic acid has been shown to significantly increase diagnostic accuracy in the detection and characterization of liver abnormalities.Classic imaging characteristics of common liver lesions,including their behaviour on gadoxetic acid enhanced MRI,have been described in literature over recent years.It is important to be familiar with the typical aspects of these lesions as well as know the uncommon and overlapping imaging features to reach an accurate diagnosis.In this article,we will review the well-described characteristic imaging findings of common and rare focal liver lesions and present several challenging cases encountered in the clinical setting,namely hepatocellular adenoma,focal nodular hyperplasia,hepatic angiomyolipoma,hepatocellular carcinoma,intrahepatic cholangiocarcinoma,neuroendocrine tumours as well as a pleomorphic liposarcoma of the liver.

Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture

To investigate presence and extent of eosinophilic cholangitis (EC) as well as IgG4-related disease in patients with indeterminate biliary stricture (IBS).METHODSAll patients with diagnosis of sclerosing cholangitis (SC) and histopathological samples such as biopsies or surgical specimens at University Hospital Frankfurt from 2005-2015 were included. Histopathological diagnoses as well as further clinical course were reviewed. Tissue samples of patients without definite diagnosis after complete diagnostic work-up were reviewed regarding presence of eosinophilic infiltration and IgG4 positive plasma cells. Eosinophilic infiltration was as well assessed in a control group of liver transplant donors and patients with primary sclerosing cholangitis.RESULTSone hundred and thirty-five patients with SC were included. In 10/135 (13.5%) patients, no potential cause of IBS could be identified after complete diagnostic work-up and further clinical course. After histopathological review, a post-hoc diagnosis of EC was established in three patients resulting in a prevalence of 2.2% (3/135) of all patients with SC as well as 30% (3/10) of patients, where no cause of IBS was identified. 2/3 patients with post-hoc diagnosis of EC underwent surgical resection with suspicion for malignancy. Diagnosis of IgG4-related cholangitis was observed in 7/135 patients (5.1%), whereas 3 cases were discovered in post-hoc analysis. 6/7 cases with IgG4-related cholangitis (85.7%) presented with eosinophilic infiltration in addition to IgG4 positive plasma cells. There was no patient with eosinophilic infiltration in the control group of liver transplant donors (n = 27) and patients with primary sclerosing cholangitis (n = 14).CONCLUSIONEC is an underdiagnosed benign etiology of SC and IBS, which has to be considered in differential diagnosis of IBS.

Powell dynamic identification of displacement parameters of indeterminate thin-walled curve box based on FCSE theory

The FCSE controlling equation of pinned thinwalled curve box was derived and the indeterminate problem of continuous thin-walled curve box with diaphragm was solved based on flexibility theory. With Bayesian statistical theory,dynamic Bayesian error function of displacement parameters of indeterminate curve box was founded. The corresponding formulas of dynamic Bayesian expectation and variance were deduced. Combined with one-dimensional Fibonacci automatic search scheme of optimal step size,the Powell optimization theory was utilized to research the stochastic identification of displacement parameters of indeterminate thin-walled curve box. Then the identification steps were presented in detail and the corresponding calculation procedure was compiled. Through some classic examples,it is obtained that stochastic performances of systematic parameters and systematic responses are simultaneously deliberated in dynamic Bayesian error function. The one-dimensional optimization problem of the optimal step size is solved by adopting Fibonacci search method. And the Powell identification of displacement parameters of indeterminate thin-walled curve box has satisfied numerical stability and convergence,which demonstrates that the presented method and the compiled procedure are correct and reliable.During parameters鈥？iterative processes,the Powell theory is irrelevant with the calculation of finite curve strip element（FCSE） partial differentiation,which proves high computation effciency of the studied method.

Internal Force Analysis Due to the Supporting Translation in Statically (Indeterminate) Structures for Different Elastic Modulus

For statically indeterminate structure, the internal force will be changed with the translation of the supports, because the internal force is related to the absolute value of the stiffness EI. When the tension is different with the compression modulus, EI is the function of internal force and is not constant any more that is different from classic mechanics. In the other words, it is a nonlinear problem to calculate the internal force. The expression for neutral axis of the statically indeterminate structure was derived in the paper. The iterative program for nonlinear internal force was compiled. One case study was presented to illustrate the difference between the results using the different modulus theory and the single modulus theory as in classical mechanics. Finally, some reasonable suggestions were made for the different modulus structures.

A Two-Stage Method for an Approximate Calculation of Statically Indeterminate Trusses

The paper presents the principles of a method, which in two simple stages makes possible to carry out the statically calculation of values of forces acting in the fiat static indeterminate trusses. In each stage, it is considered the static determinate truss, scheme of which is obtained after remove the suitable number of members from the basic static indeterminate truss. The both intermediate statically determinate trusses are of the same clear span and they are loaded by forces of half values applied to the corresponding truss nodes. The method applies one of the typical procedures of calculation of the statically determinate trusses and then it is applied in an appropriate way the rule of superposition for obtaining the final values of forces acting in particular members of the basic truss. The values of forces calculated in this way are of a very close approximation to the force values determined in the special and complex ways being considered as the exact calculation methods. The proposed method can be useful mostly but not only for the initial structural design of such systems. The simplicity of the two-stage method justifies an assumption that it can be relatively easy and worthy to adjust to the requirements of the computer aided technology of statically calculation of the complex forms of trusses.

Investigation on the Indeterminate Information of Rock Joint Roughness through a Neutrosophic Number Approach

To better estimate the rock joint shear strength,accurately determining the rock joint roughness coefficient(JRC)is the first step faced by researchers and engineers.However,there are incomplete,imprecise,and indeterminate problems during the process of calculating the JRC.This paper proposed to investigate the indeterminate information of rock joint roughness through a neutrosophic number approach and,based on this information,reported a method to capture the incomplete,uncertain,and imprecise information of the JRC in uncertain environments.The uncertainties in the JRC determination were investigated by the regression correlations based on commonly used statistical parameters,which demonstrated the drawbacks of traditional JRC regression correlations in handling the indeterminate information of the JRC.Moreover,the commonly used statistical parameters cannot reflect the roughness contribution differences of the asperities with various scales,which induces additional indeterminate information.A method based on the neutrosophic number(NN)and spectral analysis was proposed to capture the indeterminate information of the JRC.The proposed method was then applied to determine the JRC values for sandstone joint samples collected from a rock landslide.The comparison between the JRC results obtained by the proposed method and experimental results validated the effectiveness of the NN.Additionally,comparisons made between the spectral analysis and common statistical parameters based on the NN also demonstrated the advantage of spectral analysis.Thus,the NN and spectral analysis combined can effectively handle the indeterminate information in the rock joint roughness.

A METHOD OF ADJUSTING BAR-LENGTH OF STATICALLY INDETERMINATE TRUSS FOR INCREASING ITS LOAD CAPACITY

Based on the character of the internal force distribution of the statically indeterminate truss, the elements stresses were changed by adjusting the length of bars to increase load capacity of structure. The efficiency of the method is illustrated by several examples.

Strong/weak limits and strong/weak differentials of multi-variable indeterminate forms. I: Deduction and geometric illustration

Strong and weak limits as well as strong and weak differentials of multi-variable indeterminate forms are discussed based on the thorough exploration of differentiation to solve the strong and weak limits and differentials of unitary indeterminate forms. The fruit of this work is going to be reported in three parts. The first part presents the standard analysis on this subject which supplements, systematizes and advances L. Hospital抯 principles on differential calculus by applying special ,general, and limit guaranteeing theories together with K(t) and XhK0 theories. The combination of theoretical analysis and geometric signification makes the derivation intuitional, visual and easy to perceive.

Strong/weak limits and strong/weak differentials of multi-variable indeterminate forms. III: Transformations

Various transforms of the indeterminate forms are presented in this part, which include simplification in spherical coordinates, origin translation, axis alteration, transformation of limit conservation and application of Xh?K0. Fundamental factors for numerical simplification are provided respectively for bi-variable indeterminate forms, tri-variable indeterminate forms and the universal extending multiplier.

Strong/weak limits and strong/weak differentials of multi-variable indeterminate forms. II: Supplementary annotations and analysis

Supplementary annotations on special forms 1to 4, discussion on the general characteristics of K(t) and K(t, t), and analyses on two noticeable limits are presented in this part. It is demonstrated that strong and weak parabolic transforms can be employed to change the standard form of a multi-variable indeterminate form into xmK type, hence to derive the standard formulae of the limit and the differential.

Tumor-Associated Autoantibodies: Re-Optimization of EarlyCDT-Lung Diagnostic Performance and Its Application to Indeterminate Pulmonary Nodules

Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish malignant from benign pulmonary nodules would be hugely beneficial. EarlyCDT-Lung measures serum autoantibodies to tumor-associated antigens and has found clinical acceptance to aid early detection of lung cancer for high risk patients. However performance was optimized for screening. The construction of a receiver-operating characteristic (ROC) curve would enable optimization of performance for alternative settings, including nodule malignancy. Methods: A Monte-Carlo search method was used to construct a ROC curve using a case-control cohort, enabling high and low specificity versions of EarlyCDT-Lung to be determined. These were used for a theoretical evaluation of a nodule cohort, and positive predictive value (PPV) was calculated under the assumption of independence of risk source. Patients or their nodules are typically classified into three risk groups: low (0% - 10%), intermediate (10% - 65%) and high (>65%) risk of malignancy. The predicted shift in risk group by application of the high and low specificity versions, along with the current commercial EarlyCDT-Lung, was then estimated. Results: The ROC curve, with an area under the curve of 0.743, was constructed. The high specificity (98%), low specificity (49%) and current commercial (91% specificity) versions of EarlyCDT-Lung re-classified 27%, 23% and 26% of intermediate nodules, respectively, to either a higher (10%, 8% and 10%) or lower (17%, 15% and 16%) risk group. Conclusion: A ROC curve was constructed to allow performance prediction of EarlyCDT-Lung at different specificities in the indeterminate nodule setting. This enabled risk re-classification of intermediate risk nodules, and could therefore facilitate alternative more appropriate intervention. We have shown how a multivariate biomarker test can add to the interpretation of pulmonary nodules and therefore aid patient management.