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1.
Diagnostics (Basel) ; 13(16)2023 Aug 17.
Article En | MEDLINE | ID: mdl-37627957

We aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as "sternal", "manubrium", and "metastasis" within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females' ages were between 34 and 80 (mean of 57.28) and the males' ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

2.
Diagnostics (Basel) ; 13(8)2023 Apr 07.
Article En | MEDLINE | ID: mdl-37189469

Metastasis to the pancreas represents a small proportion of all pancreatic malignancies. Among primary tumors that metastasize to the pancreas, renal cell carcinoma (RCC) is one of the most common causes of metastatic pancreatic lesions. We herein report a case series of three patients with pancreatic metastasis from RCC. The first is a 54-year-old male with a history of left nephrectomy for RCC, in whom an isthmic pancreatic mass suggestive of a neuroendocrine lesion was found during oncological follow-up. Endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) identified pancreatic metastasis of RCC and the patient was referred for surgery. The second case is a 61-year-old male, hypertensive, diabetic, with left nephrectomy for RCC six years previously, who complained of weight loss and was found with a hyperenhancing mass in the head of the pancreas and a lesion with a similar pattern in the gallbladder. EUS-FNB from the pancreas proved to be a metastatic pancreatic lesion. Cholecystectomy and treatment with tyrosine kinase inhibitors were recommended. The third case is a 68-year-old dialysis patient referred for evaluation of a pancreatic mass, also confirmed by EUS-FNB, who was started on sunitinib treatment. We report a literature summary on epidemiology and clinical features, diagnosis and differential diagnosis and treatment and outcomes in pancreatic metastasis of RCC.

3.
Cancers (Basel) ; 14(24)2022 Dec 10.
Article En | MEDLINE | ID: mdl-36551569

Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13%; EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time.

4.
Life (Basel) ; 12(12)2022 Dec 16.
Article En | MEDLINE | ID: mdl-36556492

The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.

5.
Exp Ther Med ; 22(3): 959, 2021 Sep.
Article En | MEDLINE | ID: mdl-34335901

The present study constitutes a retrospective study for patients with hyperparathyroidism surgically operated on at the Department of Thoracic Surgery of the Central Military Emergency University Hospital 'Dr. Carol Davila', Bucharest, Romania (SUUMC), over a period of 6 years. The study aimed to elucidate the diagnostic and surgical attitude for an effective treatment, practiced at SUUMC, Romania. The study group included 55 patients: 41 women and 14 men, diagnosed at the endocrinology department, who underwent various personalized surgeries (Kocher modified incision) for typical and ectopic locations of parathyroid pseudotumor formations (hyperplasia and parathyroid adenoma), to cure the disease. The recommended protocol was followed by immediate and 30-day postoperative evaluation which showed normalization of the blood tests, and improved clinical and imaging anomalies. In conclusion, the thoracic surgeon has the necessary knowledge to perform surgery at the cervical, thoracic-cervical and mediastinal levels. Postoperative, the results of laboratory tests for calcium (Ca) and parathyroid hormone (PTH) gradually returned to normal, as can be seen from the statistical study.

6.
Front Oncol ; 11: 697409, 2021.
Article En | MEDLINE | ID: mdl-34277443

Colorectal cancer (CRC) is often characterized by mutations and aberrant DNA methylation within the promoters of tumor suppressor genes and proto-oncogenes. The most frequent somatic mutations occur within KRAS and BRAF genes. Mutations of the KRAS gene have been detected in approximately 40% of patients, while mutations in BRAF have been detected less frequently at a rate of 10%. In this study, the DNA methylation levels of 22 candidate genes were evaluated in three types of tissue: mucosal tumoral tissue from 18 CRC patients, normal adjacent tissues from 10 CRC patients who underwent surgical resection, and tissue from a control group of six individuals with normal colonoscopies. A differential methylation profile of nine genes (RUNX3, SFRP1, WIF1, PCDH10, DKK2, DKK3, TMEFF2, OPCML, and SFRP2) presenting high methylation levels in tumoral compared to normal tissues was identified. KRAS mutations (codons 12 or 13) were detected in eight CRC cases, and BRAF mutations (codon 600) in four cases. One of the CRC patients presented concomitant mutations in KRAS codon 12 and BRAF, whereas seven patients did not present these mutations (WT). When comparing the methylation profile according to mutation status, we found that six genes (SFRP2, DKK2, PCDH10, TMEFF2, SFRP1, HS3ST2) showed a methylation level higher in BRAF positive cases than BRAF negative cases. The molecular sub-classification of CRC according to mutations and epigenetic modifications may help to identify epigenetic biomarkers useful in designing personalized strategies to improve patient outcomes.

7.
Cancers (Basel) ; 13(9)2021 May 08.
Article En | MEDLINE | ID: mdl-34066837

(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17-12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09-15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.

8.
Mol Clin Oncol ; 8(4): 595-599, 2018 04.
Article En | MEDLINE | ID: mdl-29541469

Although gastric metastases have been estimated to occur in less than 2% of cancer patients, an increased use of upper digestive tract endoscopy allows for a higher detection of secondary gastric tumors. We describe the case of a 66-year-old male patient presenting with mild pain in the sternum and upper abdominal area. Physical examination revealed a right parietal skull tumor, with no other significant clinical changes. Upon exclusion of an acute coronary syndrome, upper digestive tract endoscopy was performed, showing the presence of an ulcerated tumor located in the gastric fundus. Histopathologic examination of the biopsy sample and immunohistochemical tests suggested a pulmonary origin of the gastric tumor. Whole body computer tomography showed the presence of tumors in the gastric fundus, left lung, liver, kidneys, bones and brain. Transbronchial biopsy of the lung tumor certified the diagnosis of non-small cell lung cancer, with the same immunohistochemical profile as the gastric tumor. Hence, it was considered the origin of the metastases. Biopsy of the skull tumor also had the identical tumor histology. Whole brain radiotherapy was performed for the brain metastases and subsequent chemotherapy was administered. Although non-specific, gastrointestinal signs and symptoms occurring in lung cancer patients should alert the clinicians as to the possibility of gastrointestinal metastases and prompt endoscopic evaluation.

9.
Rom J Morphol Embryol ; 58(2): 685-688, 2017.
Article En | MEDLINE | ID: mdl-28730262

OBJECTIVES: Patients with Helicobacter pylori (HP) infection have been reported to have in addition to duodenitis architectural changes of the duodenal bulb mucosa including villous atrophy and crypt hyperplasia. We here for the first time present two cases of HP-infected adult patients with a crypt hyperplastic enteropathy also in the distal duodenum mimicking celiac disease (CD). METHODS: We evaluated separately the morphology of the anatomical bulb and distal duodenal mucosa using validated quantitative morphometric tools, i.e., the villous height (VH) and crypt depth (CrD) and their ratios. The fresh frozen samples were evaluated for the presence of the CD-specific transglutaminase 2-targeted subepithelial IgA deposits. RESULTS: Both patients had celiac-type crypt hyperplastic mucosal injury in the distal part of the duodenum in the absence of serum autoantibodies and subepithelial IgA deposits. After two years follow-up, having still a normal gluten-containing diet, none of the patients developed CD. Moreover, in the patient re-biopsied two years later, the CD-type enteropathy had healed after HP eradication. CONCLUSIONS: Prospective studies on HP-infected patients are needed in order to confirm our findings.


Duodenum/pathology , Helicobacter Infections/diagnosis , Helicobacter pylori/pathogenicity , Female , Helicobacter Infections/pathology , Humans , Male , Middle Aged
10.
Rom J Morphol Embryol ; 58(1): 7-14, 2017.
Article En | MEDLINE | ID: mdl-28523291

This paper draws on the author's extensive experience in the clinical research focused on the implementation of the new biotechnologies able to identify precancerous cervical lesions and is intended to be a systematic approach to new achievements. The goal of this review is to provide updated information concerning the significance of each biotechnology used in clinical medicine to screen women for cervical cancer or to allow a pertinent discrimination between spontaneous remission lesions and progressive lesions. The data is arranged according to the most widely used biotechnologies and the worldwide recommendations of specialized guidelines.


Biotechnology/methods , Colposcopy/methods , Immunohistochemistry/methods , Mass Screening/methods , Precancerous Conditions/diagnosis , Uterine Cervical Neoplasms/diagnosis , Female , Humans
11.
Oncol Lett ; 11(1): 189-193, 2016 Jan.
Article En | MEDLINE | ID: mdl-26870187

Neuroendocrine carcinomas of the uterine cervix are rare, but extremely aggressive, gynecological malignancies that are associated with an overall poor prognosis. The present study reports the case of a 41-year-old patient diagnosed with large cell neuroendocrine cervical tumor. A radical total hysterectomy with bilateral adnexectomy, pelvic and lymph node dissection was performed. The post-operative course was uneventful, and the patient was discharged on post-operative day 8.

12.
Rom J Morphol Embryol ; 57(4): 1365-1370, 2016.
Article En | MEDLINE | ID: mdl-28174805

Epithelioid trophoblastic tumor (ETT) is a very rare case of malignant trophoblastic tumor, which can occur particularly during the fertile age of women with a long history of abortion and delivery. ETT originates from the intermediate trophoblastic cells of chorion laeve. The main features of this tumor include lack of vessels within the tumor, nuclear hyperchromasia and pleomorphism and a large zone of necrosis and hyalinization. The clinical features of ETT are specific to each case and often consist of vaginal bleeding or amenorrhea in the absence of other complains. The beta-human chorionic gonadotropin (ß-hCG) serum level cannot be an absolute criterion useful in defining diagnosis. The right diagnosis can only be established by a histopathological examination of the tissue picked-up via intrauterine curettage. This paper describes the case of a 35-year-old woman who required gynecological investigation for amenorrhea. The diagnosis established by biopsic curettage and the clinical evolution have influenced the physician's decision to perform hysterectomy. The only method to differentiate between the microscopic diagnosis of ETT and choriocarcinoma was the immunohistochemical staining of trophoblastic cells for cytokeratin AE1÷AE3, p63, Ki67. Despite the diagnosis of malignity, this tumor does not usually require a recommendation for chemotherapy and does not seem to have a bad prognostic. However, these data do not rule out that clinical behavior is sometimes difficult to predict. We analyzed the clinical and histology criteria in line with the data published in literature.


Epithelioid Cells/pathology , Trophoblastic Neoplasms , Adult , Female , Humans , Trophoblastic Neoplasms/pathology , Trophoblastic Neoplasms/therapy
13.
Maedica (Bucur) ; 11(2): 109-114, 2016 Jun.
Article En | MEDLINE | ID: mdl-28461829

BACKGROUND: Once considered a disease of childhood, celiac disease (CD) is now seen quite frequently in adults also, but with different and various clinical presentation. Little data is currently available about pediatric and adult CD features in Romanian patients. METHODS: 38 newly-diagnosed CD patients (17 adults and 21 children) were recruited for this study. The two groups (adult and pediatric) were compared regarding demographic, clinical, serologic and histological data. RESULTS: Regarding demographic data, female gender was predominant in both groups (71% and 67% respectively). Median age was 42 (range 23-83) in the adult CD group and 4 (1-17) in the pediatric CD group. Classic presentation was more frequently seen in children than adults (62% vs. 53%). Altered liver function tests, anemia and iron deficiency were more prevalent in the pediatric group. Children with CD also had higher titers of tTG antibodies (81% over 200 U/l, compared to 29% adults) and a higher frequency of destructive histology on small bowel biopsy (95% Marsh>3a, compared to 76% adults). CONCLUSION: Significant differences in pediatric and adult CD were seen in our study cohort, regarding clinical, laboratory and histological parameters. CD manifests differently in children and adults.

14.
J Gastrointestin Liver Dis ; 24(3): 369-73, 2015 Sep.
Article En | MEDLINE | ID: mdl-26405709

BACKGROUND: Primary intestinal lymphangiectasia (Waldmann's disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia. CASE PRESENTATION: We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed. A low-fat diet along with nutritional therapy with medium-chain triglyceride supplementation improved the protein-losing enteropathy, but did not solve the anemia. Octreotide was also unsuccessful, and after attempting angiographic embolization therapy, limited small bowel resection together with antiplasmin therapy managed to correct the anemia and control the exudative enteropathy. CONCLUSIONS: Although primary intestinal lymphangiectasia is usually adequately managed by nutritional therapy, complications such as anemia can occur and can prove to be a therapeutic challenge.


Anemia/etiology , Lymphangiectasis, Intestinal/complications , Lymphedema/complications , Anemia/blood , Anemia/diagnosis , Anemia/therapy , Antifibrinolytic Agents/therapeutic use , Biopsy , Chronic Disease , Diet, Fat-Restricted , Dietary Supplements , Digestive System Surgical Procedures , Embolization, Therapeutic , Endoscopy, Gastrointestinal , Humans , Lymphangiectasis, Intestinal/diagnosis , Lymphangiectasis, Intestinal/therapy , Lymphedema/diagnosis , Lymphedema/therapy , Male , Octreotide/therapeutic use , Protein-Losing Enteropathies/etiology , Protein-Losing Enteropathies/therapy , Severity of Illness Index , Treatment Outcome , Triglycerides/administration & dosage , Young Adult
15.
Rom J Morphol Embryol ; 56(2): 601-5, 2015.
Article En | MEDLINE | ID: mdl-26193237

There is increased evidence that end-stage renal disease patients, especially the hemodialyzed population, may present various unexpected forms of complications, contributing to a poor prognosis. Furthermore, neuroendocrine tumors, rarely encountered in daily practice, present in dialyzed individuals can significantly exacerbate the inflammatory condition with negative impact on patients' quality of life. We present an unusual case of uterus neuroendocrine tumor with multiple metastases in a 49-year-old female hemodialyzed patient with a history of alcoholic liver cirrhosis and uterus fibromatous. Multiple endoscopic techniques (e.g., upper endoscopy, colonoscopy, upper and lower echoendoscopy), histological evaluation of biopsy samples from involved areas (the operatory piece) were performed in order to complete and refine the diagnosis.


Liver Cirrhosis, Alcoholic/complications , Neuroendocrine Tumors/complications , Renal Dialysis , Uterine Neoplasms/complications , Cell Differentiation , Colonoscopy , Fatal Outcome , Female , Humans , Liver Cirrhosis, Alcoholic/diagnostic imaging , Liver Cirrhosis, Alcoholic/pathology , Middle Aged , Myometrium/pathology , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Prognosis , Ultrasonography , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/pathology
16.
Rom J Morphol Embryol ; 55(2 Suppl): 635-42, 2014.
Article En | MEDLINE | ID: mdl-25178337

Complete regression of primary cutaneous melanoma is a very rare phenomenon. Only 49 cases of well-documented completely regressed primary cutaneous melanoma have been reported to date. The clinical picture and histological findings may vary considerably. The presence of regional lymphadenopathy represents a necessary requisite for the diagnosis of completely regressed primary cutaneous melanoma. However, some cases lie outside these criteria and are difficult to diagnose and classify. Moreover, completely regressed melanoma is not specifically referred to in the current AJCC (American Joint Commission on Cancer) melanoma staging system. We report three cases of completely regressed primary cutaneous melanoma. One of the cases presented with unquestionable clinical and histopathological findings of completely regressed primary cutaneous melanoma, but without concomitant regional lymph node metastasis. As expected, this patient eventually developed nodal metastatic disease. An extraordinary case of a completely regressed melanoma that appeared in association with a congenital melanocytic nevus is also documented. This case revealed a unique type of regression that affected only the melanoma. The nevus was left undisturbed by the immunological response.


Melanoma/classification , Melanoma/diagnosis , Neoplasm Regression, Spontaneous/pathology , Adult , Fatal Outcome , Female , Humans , Male , Melanoma/pathology , Melanoma/therapy , Middle Aged , Pigmentation , Skin Neoplasms , Melanoma, Cutaneous Malignant
17.
Rom J Morphol Embryol ; 55(2): 407-12, 2014.
Article En | MEDLINE | ID: mdl-24969993

BACKGROUND: Pulmonary inflammatory myofibroblastic tumor (PIMT) is a rare disease that occurs more frequently in younger patients. Its etiopathogeny remains debated whether this is an inflammatory lesion characterized by uncontrolled cell growth or a true neoplasm. AIM: To present a case of PIMT in a young men, HIV-positive since childhood. Patient, Methods and Results: We report the case of an HIV-positive patient, aged 21 years, with collapsed immunity (CD4=23 cells/mm3), which in the second half of 2009 was clinically and radiologically diagnosed with recurrent right pneumonia. Serological tests were negative for Mycoplasma, Epstein-Barr and HHV-8 and positive for cytomegalovirus (CMV). Further monitoring of this episode raises imaging suspicion of the tumor in right upper pulmonary lobe. A lung wedge biopsy by thoracotomy was performed. The result of histopathological examination was suggestive for Kaposi sarcoma but required an immunohistochemical examination (vimentin, smooth muscle actin, CD34, anaplastic lymphoma kinase, CK7, L26/CD20, CD38, CD68), which established diagnosis of PIMT. In our case, we noticed a favorable evolution under antiretroviral treatment (by increasing CD4 count - immunity slowly improved), broad-spectrum antibiotics, and steroidal anti-inflammatory treatment, with regression of PIMT over eight months. CONCLUSIONS: Although inflammatory myofibroblastic tumor (IMT) is rare, it should be considered in the differential diagnosis of pulmonary tumoral lesions in young adults. This is the first PIMT case in an HIV-positive patient described in Romania. Even good response in such cases was noticed after surgical treatment, in our case we achieved complete remission of the disease with anti-inflammatory steroidal therapy and combined antiretroviral therapy (cART). As other infectious etiologies, CMV also could represent a trigger for developing a pulmonary inflammatory myofibroblastic tumor.


Acquired Immunodeficiency Syndrome/complications , Lung Neoplasms/complications , Neoplasms, Muscle Tissue/complications , Pneumonia/complications , Humans , Lung Neoplasms/diagnosis , Male , Neoplasms, Muscle Tissue/diagnosis , Pneumonia/diagnosis , Pneumonia/etiology , Young Adult
18.
BMC Gastroenterol ; 13: 115, 2013 Jul 12.
Article En | MEDLINE | ID: mdl-23849178

BACKGROUND: Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose. METHODS: As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects. RESULTS: In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive. CONCLUSION: The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.


Autoantibodies/blood , Celiac Disease/diagnosis , GTP-Binding Proteins/immunology , Point-of-Care Systems , Transglutaminases/immunology , Adolescent , Adult , Aged , Biomarkers/blood , Child , Child, Preschool , Erythrocytes/enzymology , Humans , Immunoglobulin A/blood , Infant , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Middle Aged , Protein Glutamine gamma Glutamyltransferase 2 , Young Adult
19.
Rom J Morphol Embryol ; 54(1): 43-9, 2013.
Article En | MEDLINE | ID: mdl-23529308

Tumor infiltrating lymphocytes (TIL), as a microenvironment component were studied in various epithelial tumors, with contradictory results. Recent data about regulatory T-cells (Treg) revealed new explanations for pro- and anti-tumor implications of TIL. Tregs immunoprofile was recently completed with Foxp3 expression. A T-cell fraction (Th) is producing cytokine IL17 and is now considered acting in tumor progression. Our study aimed to analyze immunohistochemically (IHC) Foxp3+ and IL17 expression in resected lung adenocarcinomas, since they could become possible targets in the antitumor immunotherapy. The studied material was represented by paraffin-embedded tumor fragments from 59 patients with TIL identified on HE staining. The antibodies used were Foxp3 and IL17. The statistical analysis used logistical regression on SPSS19 software (Chicago, IL, USA). TIL was usually mild or scarce. A positive statistic correlation resulted between the amounts of TIL in peritumoral and intratumoral location but without correlation to histopathological grading. Foxp3 and IL17 were present in TIL lymphocytes, tumor cells and fibroblasts; IL17 was expressed also in periendothelial cells (PEC). Foxp3 positivity was significantly correlated for lymphocytes÷tumor cells, lymphocytes÷fibroblasts and tumor cells÷fibroblasts, suggesting their concerted action. Tumor cells and lymphocytes Foxp3 expression was inversely correlated with the amount of TIL. Between lymphocytic Foxp3 and PEC IL17, we found a weak negative correlation. The TIL had a quite positive correlation with PEC IL17. In these conditions, Foxp3 could be a mediator of the tumor cells inhibitory aggression upon the immune system and could be used as a molecular target for biological antitumor therapy.


Adenocarcinoma/metabolism , Forkhead Transcription Factors/biosynthesis , Interleukin-17/biosynthesis , Lung Neoplasms/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Female , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Prognosis
20.
Rom J Morphol Embryol ; 54(4): 1169-71, 2013.
Article En | MEDLINE | ID: mdl-24399019

The neuroendocrine tumors (NETs) have an increased incidence related to the age. Secondary osteoporosis might be found in patients with bone metastases and in those with NETs associated Cushing's disease or primary hyperparathyroidism. Primary osteoporosis might be found in postmenopausal women, but in case with non-metastatic NET as G1 NET it is difficult to establish the NET contribution to the bone loss. We present the case of a 53-year-old female accidentally diagnosed with G1 lung NET after surgery of the tumor. The immunohistochemistry pointed positive reaction for CHROMO, SYN and negative for CK7 and TTF1, and a Ki67 of 1-2% (well-differentiated neuroendocrine tumor). The central Dual X-Ray Absorptiometry (DXA) showed osteoporosis based on a T-score of -3. The patient had normal neuroendocrine markers and she was asymptomatic. She remained so for one year and the only therapy provided was weekly alendronate with adequate vitamin D and calcium supplements. Based on the pathological and immunohistochemistry profile, the low risk NET was diagnosed. We encourage the skeletal status assessment as central DXA in postmenopausal women with NETs, regardless clinical evidence of bone loss. The future will provide more epidemiological and pathogenic connections between the two dynamic fields of medicine as neuroendocrine tumors and osteoporosis.


Cell Differentiation , Incidental Findings , Neuroendocrine Tumors/complications , Neuroendocrine Tumors/pathology , Osteoporosis/complications , Osteoporosis/pathology , Absorptiometry, Photon , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Neuroendocrine Tumors/diagnostic imaging , Osteoporosis/diagnostic imaging , Synaptophysin/metabolism
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