Endovascular Intervention Reduces Thrombosis Risk in Retrievable Inferior Vena Cava Filters: A Multicenter Propensity-Matched Analysis.

The detection of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human epidermal growth factor receptor 2 (HER-2) is important for the stratification of breast cancer and the selection of therapeutic modalities. This study aimed to determine the quantitative expression of ER, PR and HER-2 using Immunohistochemistry and their correlation with quantitative baseline Ct values measured using Quantitative Polymerase Chain Reaction (PCR). This study also assessed the use of fresh breast tissue biopsies preserved in RNAlater solution in the quantitative detection of these receptors using PCR technique. The study evaluated 20 matched formalin fixed paraffin embedded and RNAlater preserved samples for ER, PR, and HER-2 using IHC and quantitative PCR technique. One portion of the breast tissue biopsy was fixed immediately in 10% neutral buffered formalin and another was preserved in RNAlater. After the histological confirmation of breast cancer by the H&E technique, formalin fixed paraffin embedded tissues (FFPE)—positive cases were matched with their corresponding RNAlater samples for IHC and qPCR. The extracted RNA was quantified using Nanodrop technology, resulting into complementary DNA. ER and PR using IHC were expressed in 60% (n = 12) of the study samples and were negative in 40% (n = 8) of samples. HER-2 was negative in 70% (n = 14) of study samples, 25% (n = 5) positive, and 5% (n = 1) equivocal. With the quantitative expression of ER, PR, and HER-2 being reported in the IHC triple—negative breast cancer cases. The mean Ct values for the hormonal receptors correlated with what has been previously studied with ER at 19.631, PR at 25.410 and HER-2 at 25.695. There was no statistically significant difference between the mean Ct values of RNAlater and FFPE with their P-values being 0.9919, 0.0896 and < 0.0001 for ER, PR, and HER-2 respectively. P-values; 0.9919 and 0.0896 for ER and PR respectively being greater than 0.05 it’s a borderline significance although HER-2 had a statistical significance. With a concordance in the detection of these breast cancer hormonal receptors, qPCR can be used in our setting considering the delays that may be associated in following the samples through IHC processing.

Periodontal and endodontic infections are interrelated and most common during routine dental practice. Palatogingival groove, a morphological anomaly usually reported on the palatal aspect of maxillary incisors, cause periodontal attachment loss and alveolar bone destruction and finally tooth loss. Unknown etiology was reported for the developmental defect, develops in to pathological condition only when the there is a discontinuity in the epithelial attachment. Early diagnosis and proper selection of therapeutic modalities helps in preservation of involved tooth. Milder cases were treated by saucerization, odontoplasty and strict oral hygiene maintenance protocol. Moderate case was treated by open flap debridement, regenerative applications such as bone graft and membrane placement. PGG restored using various restorative material and seal the morphology. Clinical diagnosis become unnoticed in most cases, hence proper diagnosis and therapeutic interventions are of prime importance in PGG management.

Abstract Introduction: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt the function of polarized molecules within cancer cells. Initial data showed an anti-mitotic effect on cancerous cells whilst more recent findings confirmed additional effects such as downregulation of DNA double strand break repair, replication stress, upregulation of autophagy, and immunogenic cell death. Identification of TTFields-driven alterations in pan-cancer and tumor specific pathway is needed to aid selection of therapeutic modalities to be applied concomitant with TTFields for improved treatment outcomes. The aim of this study was to identify common pathways involved in the response to TTFields by comparing transcriptomics of various tumor type. Methods: Control and TTFields-treated non-small cell lung carcinoma cell lines and animal model, glioblastoma (GBM) cell lines and patient-derived cell lines, and a hepatocellular carcinoma animal model were examined. Samples from GBM patients treated with concomitant TTFields and temozolomide (TMZ) were compared to samples from patients treated with TMZ alone. A list of differentially expressed genes (DEGs) was generated from transcriptomics analysis. Enrichment analysis was conducted according to the Gene Set Enrichment Analysis (GSEA) of MSigDB, Reactome, and Kegg pathway databases. Significantly overlapping pathways were identified using ActivePathways package according to the Reactome and Kegg gene sets, and an enrichment map was created according to the number of datasets supporting each pathway. Results: DEGs in response to TTFields application included genes of the cytoskeleton, immune system, and some secretion proteins. Common pathways downregulated by TTFields (negative GSEA) included DNA repair, DNA and RNA synthesis, and cell cycle regulation, specifically the G2M checkpoint, E2F targets, and Myc targets. Common pathways upregulated by TTFields (positive GSEA) included the immune response, specifically complement cascades, coagulation, and lysosome activity. ActivePathways enrichment map results agreed with the gene set enrichment results, and revealed additional pathways involved in the response to TTFields, such as SUMOylation, metabolism of carbohydrates, unfolded protein response, and signaling by interleukins. Conclusions: Transcriptomic analysis revealed common pathways involved in the responses to TTFields, regardless of the origin of the sample. Some identified pathways were in line with previously demonstrated effect of TTFields, such as mitotic interference, inhibition of DNA damage repair and upregulation of the innate immune response. New pathways revealed in this work support the examination of novel combination strategies with TTFields to increase the therapeutic effect in patients bearing various solid tumor types. Citation Format: Kerem Wainer-Katsir, Gitit Lavy-Shahaf, Shiri Davidi, Sara Jacobovitch, Tali Voloshin, Itai Tzchori, Yaara Porat, Lianghao Ding, Michael Story, Niv Pencovich, Ilan Volovitz, Joshua Branter, Stuart J. Smith, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Transcriptomics analysis for identification of pathways involved in the response to Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1866.

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. The selection of therapeutic modalities and the prognosis of affected patients are well known to be dependent not only on the tumor burden but also on the hepatic reserve function. Antiviral treatments for chronic hepatitis related to a viral infection and an increase in cases of nonviral HCC associated with the aging of society have resulted in dramatic changes regarding the characteristics of HCC patients. With recent developments in therapeutic modalities for HCC, a more detailed assessment of hepatic function has become an important need. Studies in which the relationship of albumin-bilirubin (ALBI) grade with the prognosis of HCC patients was investigated were reviewed in order to evaluate the usefulness of newly developed ALBI and modified ALBI (mALBI) grades for HCC treatment, as those scoring methods are considered helpful for predicting the prognosis and selecting therapeutic modalities based on the expected prognosis.

Oral squamous cell carcinoma (OSCC) accounts for 95% of entire oral malignant tumors. The development as well as the distribution of many tumors such as OSCC is driven by cancer stem cells (CSCs). Sex determining region Y-box 2 (SOX2) is a functional CSCs marker; it is a transcription factor coding gene, present at chromosomal 3q26.33 area. The current study was conducted to evaluate SOX2 immunohistochemical expression in OSCC in addition to correlation of its expression in various histologic grades and the existing clinical parameters. Paraffin blocks tumor tissues from forty patients of OSCC were utilized to assess SOX2 immunohistochemical expression. The present study demonstrated that SOX2 expression displayed highly significant inverse association with histologic differentiation of OSCC (P=0.001), clinical stages (P=0.007) and lymph node metastases (LNM) (P=0.035). The current study recommended that, SOX2 expression might be utilized as a prognostic predictor for OSCC, and might help in establishment of the diagnosis as well as proper selection of therapeutic modality of cancers.

PurposeIdentification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield.Materials and MethodsIn this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT).ResultsMRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively.ConclusionMRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.

This paper shall discuss the importance of protocol application in modern dentistry. Literature data that include recommendations and consensuses in dental practice point out to their presence in available literature, printed papers, reviewed journals and supplements in the form of expert group conclusions. It should be noted that the protocols most commonly rely on valid postulates of different branches of medicine, supported by specific conditions of the environment in which they are implemented. Additionally, in our settings, applicable dentistry protocols are the result of requirements that institutions and practices should fulfil according to renewable accreditation, as well as following recommendations given in the good clinical practice guidelines with different binding obligations levels. Certain protocols offer therapeutic modalities categorized into classes intended to help users to select appropriate treatments. The second part of this paper shall address one such protocol which classifies partially edentulous patients. The emphasis is on the partial edentulism classification recommended by The American College of Prosthodontists (ACP), which relies on four diagnostic criteria essential for therapeutic decision. Edentulous areas location and extent, abutment teeth health, occlusion model, and residual ridge characteristics represent the parameters which have defined the four classes of partial edentulism of different complexity. In this way, comprehensive approach to the clinical status of the patients has, for the first time been offered to the dental practitioners assuring, among others, higher uniformity of professional attitudes in selection of therapeutic modalities.

Pulmonary arterial hypertension is a progressive and debilitating disorder with an associated high morbidity and mortality rate. Significant advances in our understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary hypertension have occurred over the past several decades. This has allowed the development of new therapeutic options in this disease. Today, our selection of therapeutic modalities is broader, including calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase inhibitors, and soluble guanylate cyclase stimulators, but the disease remains fatal. This underscores the need for a continued search for novel therapies. Several potential pharmacologic agents for the treatment of pulmonary arterial hypertension are under clinical development and some promising results with these treatments have been reported. These agents include rho-kinase inhibitors, long-acting nonprostanoid prostacyclin receptor agonists, tyrosine protein kinase inhibitors, endothelial nitric oxide synthase couplers, synthetically produced vasoactive intestinal peptide, antagonists of the 5-HT2 receptors, and others. This article will review several of these promising new therapies and will discuss the current evidence regarding their potential benefit in pulmonary arterial hypertension.

Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

Large cell carcinoma of lung: On the verge of extinction?

Objectives To evaluate the application of preoperative endoscopic ultrasonography (EUS) in assessment of invasive risk and selection of therapeutic modalities for gastric stromal tumors (GST). Methods The clinical data of 135 patients with GST admitted in our hospital from January 2011 to January 2012 were retrospectively analyzed. The invasion extent of GST was assessed by image of EUS before surgery, and compared with pathological results after surgery; the Fletcher 4-tier system was used for predicting the aggressiveness of GST. The selection of therapeutic modalities in 38 patients, who underwent surgical treatment was analyzed. Results No specific clinical manifestations were noticed, but some patients with enormous GST had symptoms of ulcer, hematemesis, and melena. Among 135 patients 97 cases received conservative treatment and followed up; in remaining 38 cases, according to invasion risk assessed by EUS, there were 9 cases in low risk, 18 in intermediate risk and 11 in high risk. The surgical modalities were selected based on the risk assessment: endoscopic therapy was performed in 15 cases, laparoscopic with gastroscopic surgery in 17 cases and laparotomy in 6 cases. The coincidence rate of diagnosis between preoperative EUS and postoperative pathological examination was 79.0%. Conclusions Preoperative endoscopic ultrasonography is of value in assessment of invasion risk and selection of appropriate therapeutic modalities for gastric stromal tumors. Key words: Gastrointestinal stromal tumor; Endosonography; Diagnosis

Background: Salivary gland tumours comprise a significant proportion of oral tumours and are the next common neoplasm of the mouth after squamous cell carcinoma. These neoplasm’s have widely variable histopathologic and biologic characteristics, which makes it difficult to determine the pathogenesis and selection of therapeutic modalities. Alteration in some proto-oncogenes and tumour suppressor genes may lead to the development and progression of these tumours. Aim: The purpose of this study was to analyze the immune histochemical expression of Bcl-2 and epithelial podoplanin and lymph angiogenesis in benign and malignant salivary gland tumours. Material and method: The sample consisted of 20 formalin-fixed paraffin embedded blocks of benign and malignant salivary glands tumours. Immunohistochemical staining procedure was performed using monoclonal anti Bcl-2 antibody and D2-40 antibody. The sections were evaluated for Bcl-2 and epithelial podoplanin expression and D2-40 positive lymphatic vessels. Results and conclusion: Bcl-2 showed positive immune expression in all benign and malignant salivary gland tumours with mucoepidermoid carcinomas showing most intense expression. Podoplanin immunostaining was also assessed, highest recorded score was in peripheral mucoepidermoid carcinoma (10.4? 3.05). Lymphatic micro vessel density expressed by podoplanin showed intense score in central mucoepidermoid carcinoma (5.05? 5.0). Present investigation demonstrated positive Bcl-2, podoplanin response and Lymphatic micro vessel density in both benign and malignant salivary gland tumours suggesting that Bcl-2 and podoplanin alteration may be associated with the progression of these neoplasms.

Objectives: The selection of therapeutic modalities, including endovascular coil embolization and surgical clipping, for management of unruptured paraclinoid aneurysms, remains controversial. Detailed long-term outcome data for endovascular coil embolization of unruptured paraclinoid aneurysms are still lacking. Thus, we evaluated the safety and efficacy of coil embolization of unruptured paraclinoid aneurysms.Methods: From January 1998 to July 2010, 138 patients underwent endovascular coiling for 140 unruptured paraclinoid aneurysms. Their medical records and radiologic images were reviewed retrospectively.Results: Complications occurred in 5·7% of 140 procedures and the morbidity rate was 0·7%. Of the 140 unruptured paraclinoid aneurysms, a total of 111 aneurysms underwent follow-up imaging evaluation at 2 years or more, or showing reopening on imaging studies within 2 years (65·6±37·2 months). Multivariate analysis revealed two predictors for reopening of the aneurysms: a maximum diameter of aneurysms and a dome/neck ratio of aneurysms (P<0·05). Reopening rates of aneurysms with maximum sizes of <8, 8–10, and >10 mm were 1%, 25%, and 75%, respectively. Reopening rates were significantly different among the three groups (P<0·05). In aneurysms with a maximum diameter of 8–10 mm, there was a significant difference of dome/neck ratios between the presence and absence of reopened aneurysms (P<0·05).Discussion: The results indicate that endovascular coil embolization is a safe and effective treatment modality in selected patients with unruptured paraclinoid aneurysms. Consideration of the aneurysm size and the dome/neck ratio could assist in the selection of therapeutic modalities for these aneurysms.

The gatekeeper needs a disease management of his patients who smoke. Questionnaires will help to define the diagnosis and grade of nicotine dependence as well as the fingerprint of the patients smoking career. The ICD-10 Code and the Fagerström Nicotine Dependence Test are used. There is no therapy indicated without the optimal motivation of the patient. The transtheoretical model of Prochaska and DiClemente ist widely accepted to separate the stadium of motivation into precontemplation, contemplation, preparation and action. Many other factors like earlier experiences, catastrophe scenaries, self-efficacy and selection of therapeutic modality are important for the best outcome. 90 % of the work of a gatekeeper is minimal intervention. This means individually tailored argumentations to shift the motivation of the patient to smoking cessation. The concept is defined in the rules of the five R's with relevance, risks, rewards, roadblocks and repetition. Following these criterias, the gatekeeper gets a positive shift of his motivation in up to 60 % with only one minimal intervention. The smoking cessation guidelines through the world are very similar and show a level A grade for a synergy of behavioural therapy and medication by either nicotine replacement, bupropion or vareniclin. The selection of any other regimen is either less efficient or anecdotally and leads to a further loss of life expectancy of the smoker. The gatekeeper has the infrastructure, the know how and the confidence of his patient to act as disease manager. A successful therapy is possible over six months with about seven consultations, the success rate is expected to be even higher than the values in the medication studies. Smokers should be informed by the health organizations to avoid self therapies and look for specialists help. The gatekeeper is an ideal candidate.

Orbital vascular lesions, mainly including hemangioma and vascular malformation, are the most common disorders among orbital diseases. Vascular lesions of the orbit have clinically complicated presentations and are very hard to deal with. Selection of therapeutic modality on orbital vascular lesions requires an appropriate classification of them. An improved classification of these lesions has been proposed by the Orbital Society based on the pathological types and hemodynamic features and has been extensively used in developed countries. However, orbital vascular lesions are still being classified based on morphology in China. This classification system does not represent the pathological difference between hemangioma and vascular malformation of the orbit, nor the hemodynamic characteristics among different vascular malformations of the orbit. Morphology based classification has hampered scientific dialogue and confused clinicians, with occasionally serious consequences for patients. Thus, the use of a pathology and hemodynamics based classification of orbital vascular lesions should be highly advocated. We can expect that the use of appropriate classification can improve the management of these lesions in our country.

Ureteropelvic Junction Obstruction: Does CT Angiography Allow Better Selection of Therapeutic Modalities and Better Patient Outcome?

Double-Balloon Endoscopy for Diagnoses of Small Bowel Tumors

To determine whether preoperative helical CT angiography (CTA) with three-dimensional (3D) reconstructed images improves outcome in patients with ureteropelvic junction obstruction (UPJO) by identifying crossing vessels that may lead to surgical failure. Twenty-five patients with UPJO underwent imaging with CTA to identify crossing vessels. Patients with crossing vessels or severe hydronephrosis underwent laparoscopic dismembered pyeloplasty. In the absence of crossing vessels, and with >25% renal function on MAG-3 scan, the patient underwent an endopyelotomy. Procedures were assessed as successful by resolution of patient symptoms as well as relief of obstruction on renal scintography. Twenty-seven procedures (14 laparoscopic dismembered pyeloplasties [9 in the setting of a crossing vessel], 11 ureteroscopic endopyelotomies, and two antegrade endopyelotomy procedures) were performed. Follow-up ranged from 2.4 to 40 months (mean 21.6 months). Twenty-three of the primary procedures (92.0%) were successful. Primary laparoscopic pyeloplasty was successful in 100% of patients, while primary endopyelotomy had a success rate of 83.3%. Both secondary procedures were successful rendering the patients unobstructed and pain free. No complications occurred. The sensitivity and specificity of CTA in determining crossing vessels was 78% and 40%, respectively. Helical CT angiography with 3D reconstructed images provides valuable preoperative information in patients with UPJO scheduled for surgical intervention. This study may be used in selecting patients for proper operative intervention according to the anatomy of crossing vessels to attain high treatment success rates.

The possibility of a relationship between discographic pain responses and Minnesota Multiphasic Personality inventory scores was investigated. To determine if patients with elevated Minnesota Multiphasic Personality Inventory scale scores were more likely to report pain on the injection of a nondisrupted disc than were patients without such high scores. In general, injection into disrupted discs provokes pain, whereas injection into nondisrupted discs does not. However, discordant results are sometimes obtained and create a more difficult diagnostic challenge. The primary study group was composed of 72 patients who underwent computed tomography/discography at the three lowest lumbar levels for diagnostic purposes and completed the Minnesota Multiphasic Personality Inventory. The mean scores on the Minnesota Multiphasic Personality Inventory hypochondriasis and hysteria scales were significantly greater for patients reporting reproduction of clinical pain than for patients not reporting pain on injection of a nondisrupted disc (hypochondriasis: 77.2 vs. 68.6, P < 0.01; hysteria: 74.5 vs. 68.3, P < 0.05). The scores on the depression scale followed a similar trend (68.6 vs. 63.6, P < 0.15). Multivariate analysis, adjusting the means for possible confounding effects of age, symptom duration, and sex, did not alter the results. Discographic pain reports are not only related to anatomic abnormalities, but are influenced by personality as assessed by the Minnesota Multiphasic Personality Inventory. Patients with elevated scores on the hypochondriasis, hysteria, and depression scales may tend to overreport pain during discographic injection. Among such patients, even those with a concordant computed tomography/discographic image, selection of therapeutic modalities should be made with caution.