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TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer.
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Cuello del Útero , Mucinas , Vagina , Femenino , Humanos , Proteínas Portadoras , Moléculas de Adhesión Celular/metabolismo , Cuello del Útero/inmunología , Inmunidad Innata , Inmunoglobulina G/metabolismo , Mucinas/metabolismo , Factor Trefoil-2/metabolismo , Factor Trefoil-3/genética , Factor Trefoil-3/metabolismo , Vagina/inmunologíaRESUMEN
OBJECTIVES: To investigate associations between apparent diffusion coefficient (ADC) and cell count, Ki 67, tumor-stroma ratio (TSR), and tumoral lymphocytes in different hepatic malignancies. METHODS: We identified 149 cases with performed liver biopsies: hepatocellular cancer (HCC, n = 53), intrahepatic cholangiocarcinoma (iCC, n = 29), metastases of colorectal cancer (CRC, n = 24), metastases of breast cancer (BC, n = 28), and metastases of pancreatic cancer (PC, n = 15). MRI was performed on a 1.5-T scanner with an axial echo-planar sequence. MRI was done before biopsy. Biopsy images of target lesions were selected. The cylindrical region of interest was placed on the ADC map of target lesions in accordance with the needle position on the biopsy images. Mean ADC values were estimated. TSR, cell counts, proliferation index Ki 67, and number of tumor-infiltrating lymphocytes were estimated. Spearman's rank correlation coefficients and intraclass correlation coefficients were calculated. RESULTS: Inter-reader agreement was excellent regarding the ADC measurements. In HCC, ADC correlated with cell count (r = - 0.68, p < 0.001) and with TSR (r = 0.31, p = 0.024). In iCC, ADC correlated with TSR (r = 0.60, p < 0.001) and with cell count (r = - 0.54, p = 0.002). In CRC metastases, ADC correlated with cell count (r = - 0.54 p = 0.006) and with Ki 67 (r = - 0.46, p = 0.024). In BC liver metastases, ADC correlated with TSR (r = 0.55, p < 0.002) and with Ki 67 (r = - 0.51, p = 0.006). In PC metastases, no significant correlations were found. CONCLUSIONS: ADC correlated with tumor cellularity in HCC, iCC, and CRC liver metastases. ADC reflects TSR in BC liver metastases, HCC, and iCC. ADC cannot reflect intratumoral lymphocytes. CLINICAL RELEVANCE STATEMENT: The present study shows that the apparent diffusion coefficient can be used as a surrogate imaging marker for different histopathological features in several malignant hepatic lesions. KEY POINTS: ⢠ADC reflects different histopathological features in several hepatic tumors. ⢠ADC correlates with tumor cellularity in HCC, iCC, and CRC metastases. ⢠ADC strongly correlates with tumor-stroma ratio in BC metastases and iCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Antígeno Ki-67 , Neoplasias Hepáticas/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells. Tff1-deficient mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas, indicating that Tff1 is a tumor suppressor. As a hallmark, TFF1 contains seven cysteine residues with three disulfide bonds stabilizing the conserved TFF domain. Here, we systematically investigated the molecular forms of TFF1 in the human gastric mucosa. TFF1 mainly occurs in an unusual monomeric form, but also as a homodimer. Furthermore, minor amounts of TFF1 form heterodimers with GKN2, FCGBP, and an unknown partner protein, respectively. TFF1 also binds to the mucin MUC6 in vitro, as shown by overlay assays with synthetic 125I-labeled TFF1 homodimer. The dominant presence of a monomeric form with a free thiol group at Cys-58 is in agreement with previous studies in Xenopus laevis and mouse. Cys-58 is likely highly reactive due to flanking acid residues (PPEEEC58EF) and might act as a scavenger for extracellular reactive oxygen/nitrogen species protecting the gastric mucosa from damage by oxidative stress, e.g., H2O2 generated by dual oxidase (DUOX).
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Mucosa Gástrica/metabolismo , Factor Trefoil-1/química , Factor Trefoil-1/metabolismo , Proteínas Portadoras/metabolismo , Moléculas de Adhesión Celular/metabolismo , Cisteína/metabolismo , Humanos , Mucina 6/metabolismo , Unión Proteica , Multimerización de Proteína , Antro Pilórico/metabolismoRESUMEN
Introduction: Patients with chronic pancreatitis (CP) as well as with pancreatic head carcinoma (CA) undergo the surgical intervention named "pylorus-preserving pancreatoduodenectomy according to Traverso-Longmire (PPPD)", which allowed a comparative analysis of the postoperative courses. The hypothesis was that patients with CA would have worse general as well as immune status than patients with CP due to the severity of the tumor disease and that this would be reflected in the more disadvantageous early postoperative outcome after PPPD. Methods: With the aim of eliciting the influence of the different diagnoses, the surgical outcome of all consecutive patients who underwent surgery at the Dept. of General, Abdominal, Vascular and Transplant Surgery at the University Hospital at Magdeburg between 2002 and 2015 (inclusion criterion) was recorded and comparatively evaluated. Early postoperative outcome was characterized by general and specific complication rate indicating morbidity, mortality, and microbial colonization rate, in particular surgical site infection (SSI, according to CDC criteria). In addition, microbiological findings of swabs and cultures from all compartments as well as preoperative and perioperative parameters from patient records were retrospectively documented and used for statistical comparison in this systematic retrospective unicenter observational study (design). Results: In total, 192 cases with CA (68.1%) and 90 cases with CP (31.9%) met the inclusion criteria of this study. Surprisingly, there were similar specific complication rates of 45.3% (CA) vs. 45.6% (CP; p = 0.97) and in-hospital mortality, which differed only slightly at 3.65% (CA) vs. 3.3% (CP; p = 0.591); the overall complication rate tended to be higher for CA at 23.4% vs. 14.4% (CP; p = 0.082). Overall, potentially pathogenic germs were detected in 28.9% of all patients in CP compared to 32.8% in CA (p = 0.509), and the rate of SSI was 29.7% (CA) and 24.4% (CP; p = 0.361). In multivariate analysis, CA was found to be a significant risk factor for the development of SSI (OR: 2.025; p = 0.048); the underlying disease had otherwise no significant effect on early postoperative outcome. Significant risk factors in the multivariate analysis were also male sex for SSI and microbial colonization, and intraoperatively transfused red cell packs for mortality, general and specific complications, and surgical revisions. Conclusions: Based on these results, a partly significant, partly trending negative influence of the underlying disease CA, compared to CP, on the early postoperative outcome was found, especially with regard to SSI after PPPD. This influence is corroborated by the international literature.
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AIM: By means of the scientific description of two uncommon cases who underwent. surgical resection of multinodous goiter and following histopathological investigation revealing isolated extrapulmonary manifestation of sarcoidosis, this uncommon diagnosis including symptomatology, clinical findings, diagnostic and therapeutic management is to be illustrated. CASE DESCRIPTIONS: Diagnostics: Scintigraphy of the thyroid gland with a left-thyroid cold node; ultrasound-guided puncture (cytological investigation, non-suspicious). THERAPY: Elective thyroidectomy with no macroscopic anomalies und no abnormal aspects with regard to surgical tactic and technique. Histopathological investigation: Complete resection specimen of the thyroid gland with granulomatous inflammation consistent with sarcoidosis. CLINICAL COURSE: Uneventful with no further manifestations of sarcoidosis in the following diagnostics. DIAGNOSTICS: Ultrasound, inhomogeneous node (37×30×35 mm) of the right thyroideal gland with echo-poor parts and peripheral vascularization; scintigraphy showing marginally compensated unifocal autonomy of the thyroid gland (laboratory parameters, increased serum level of thyroglobulin [632â¯ng/mL]). THERAPY: Planned right hemithyroidectomy with confirmed nodous structure of thyroid parenchyma, without suspicious lymph nodes. Histopathological investigation: 33-mm follicular, nodular, encapsulated structure of thyroid parenchyma (diagnosed as follicular adenoma); 2nd opinion: low-grade differentiated carcinoma of thyroid gland with angioinfiltrating growth and granulomatous inflammation of sarcoidosis type. Procedural intent: After tumor-board consultation, completing thyroidectomy was performed within a 5-weeks interval (pT2 pN0[0/1] V1 L0 G3 R0) with subsequent ablating radio'active iodine therapy; 18â¯F-FDG-PET-CT (several atypical infiltrates within the right upper lobe of the lung) and bronchoscopy with no detection of further manifestation of sarcoidosis. CONCLUSION: Sarcoidosis is considered a rare granulomatous multi-locular, systemic disease of not completely known etiopathogenesis with substantial heterogeneity. In most cases, it is associated with the lung, but which can become manifest in various organs. Frequently, extrapulmonary manifestations are usually detected as histological findings by coincidence, which require further investigation to find out additional manifestations as well as to exclude florid infection or other granulomatous processes (clarifying competently differential diagnosis). Therapy is only indicated in symptomatic organ manifestations, taking into account the high rate of spontaneous healing and possible side effects.
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Bocio Nodular , Bocio , Sarcoidosis , Neoplasias de la Tiroides , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/patología , Bocio/complicaciones , Bocio/cirugía , Tiroidectomía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Inflamación/complicaciones , Bocio Nodular/complicaciones , Bocio Nodular/patología , Bocio Nodular/cirugíaRESUMEN
Objectives: The Kasabach-Merritt syndrome (KMS) is characterized by the occurrence of hemangioendothelioma (giant hemangioma with thrombosis leading to thrombocytopenia), which can be associated with disseminated intravasal coagulation. Specific aim: Based on (i) selective references from the current scientific literature and derived recommendations as well as (ii) own experiences obtained in the diagnostic and perioperative management of a representative case from daily practice in abdominal surgery, the specific case undergoing elective cholecystectomy (CCE) in KMS is to be described by means of scientific case report. Case presentation: (Patient-, finding- and treatment-specific characteristics): - Medical history: 72-years old female patient with a known KMS of the left arm and upper thorax, recurrent thrombophlebitis of the left arm and thoracic veins, previous upper GI bleeding (Mallory-Weiss syndrome in 2006, chronic anemia in lack of vitamin B12, type-A gastritis, former bleeding complications after teeth extraction/open appendectomy 1962/Caesarean section 1968 with need of transfusion [60 red blood cell packages]), intraabdominal adhesions, hypothyreosis, initial liver cirrhosis. - Symptomatology: Characteristic for cholecystolithiasis (CCL). - Diagnostic: Abdominal ultrasound shows CCL, fibroscan does not confirm suspicious cirrhosis. Laboratory parameters showed: Activation of intravasal coagulation with elevated prothrombin fragments, D-dimers and reduced antiplasmin concentration. Accelerated fibrinolysis capacity; currently, no secondary thrombocytopenia or factor-13 decrease. In addition, fibrinogen concentration within normal range, no hint onto the manifestation of an aquired von-Willebrand's syndrome. - Diagnosis: Chronic fibrosing cholecystitis in CCL after former acute cholecystitis (3â¯months ago) with indication for surgical intervention. - Therapy: Laparoscopic CCE including careful exploration of upper abdominal cavity for KMS manifestation (with no revision of bile duct) and peritoneal adhesiolysis (histological finding, chronic fibrosing cholecystitis with thickening of the wall of the gall bladder but no hint of malignancy) under perioperative prophylaxis with antibiotics and temporary cessation of platelet medication for 7â¯d preoperatively, "bridging" with low molecular weight heparin (Clexane, 1 × 40â¯mgâ¯s.c.; Sanofi-Aventis, Frankfurt/Main, Germany); 1â¯h preoperatively, 15-20â¯mg/kg body weight Cyclocapron i.v. (once again 6-8â¯h postoperatively; thereafter, 500â¯mg of Cyclocapron 4×/d until the 3rd postoperative day). - Intraoperatively: Congestion of veins but not at the immediate surgical field (gall bladder, hepatic bed of the gall bladder, Calot's triangle). - Outcome: Uneventful, in particular, no (bleeding) complications. Conclusions: If surgical approach is indicated, the intervention should be thoroughly planned (in particular, under elective circumstances) with regard to hemangioma site and extension as well as distance to the surgical field and possible surgical alternative options (surgical access site, open/laparoscopic approach etc.) to prevent - at the best possible rate - bleeding complications intra-/postoperatively and, thus, to provide adequate patient safety.
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Dedifferentiated chondrosarcoma (DDCS) is a rare malignant cartilage tumor arising out of a low-grade chondrosarcoma, whereby the well-differentiated and the dedifferentiated components coexist in the same localization. DDCS has a massively increased metastatic potential in comparison to low-grade chondrosarcoma. So far, the underlying mechanisms of DDCS development and the increased malignancy are widely unknown. Targeted DNA sequencing revealed no genetic differences between both tissue components. Besides genetic events, alterations in epigenetic control may play a role in DDCS development. In this preliminary study, we have analyzed the differential miRNA expression in paired samples of both components of four primary DDCS cases and a rare lung metastasis with both components using the nCounter MAX analysis system from NanoString technologies. We identified 21 upregulated and two downregulated miRNAs in the dedifferentiated components of the primary cases. Moreover, three miRNAs were also significantly deregulated in the dedifferentiated component of the lung metastasis, supporting their possible role in DDCS development. Additionally, validated targets of the 23 deregulated miRNAs are involved in signaling pathways, like PI3K/Akt, Wnt/ß-catenin, and TGF-ß, as well as in cellular processes, like cell cycle regulation, apoptosis, and dedifferentiation. Further investigations are necessary to confirm and understand the role of the identified miRNAs in DDCS development.
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Neoplasias Óseas , Condrosarcoma , MicroARNs , Humanos , MicroARNs/genética , Fosfatidilinositol 3-Quinasas , Neoplasias Óseas/patología , Factor de Crecimiento Transformador beta , Condrosarcoma/genética , Condrosarcoma/patologíaRESUMEN
Autoimmune gastritis (AIG) is a chronic immune-mediated inflammation of the gastric corpus/fundus mucosa leading to progressive atrophy of the oxyntic gastric glands (AOM) and their consecutive loss of function. Possible clinical consequences of AIG include iron deficiency anemia, pernicious anemia, gastric neuroendocrine tumors (gNET), and gastric adenocarcinoma. This article provides a review of interdisciplinary aspects of the diagnosis and treatment of AIG.
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Anemia Ferropénica , Enfermedades Autoinmunes , Gastritis , Neoplasias Gástricas , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/patología , Anemia Ferropénica/terapia , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/terapia , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapiaRESUMEN
Lipoblastoma is a rare benign, but highly proliferative tumor most commonly seen in early childhood. Recurrence rates are high when complete resection is unfeasible and systemic therapy is necessary. We report the case of a large, aggressive thoracic and mediastinal lipoblastoma in a 20-year-old woman, which was surgically not resectable. The tumor has been characterized extensively including molecular pathology, molecular karyotyping, conventional chromosomal analysis and in vitro-chemosensitivity testing in search for alternative therapies. Nevertheless, this did not reveal treatable targets and systemic therapies, which were based on chemosensitivity testing proved ineffective. Despite all treatment attempts, the disease showed a progressive fatal course.
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Lipoblastoma , Lipoma , Neoplasias del Mediastino , Femenino , Humanos , Preescolar , Lactante , Adulto Joven , Adulto , Neoplasias del Mediastino/patologíaRESUMEN
Background: Antibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains. Aim: To study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account. Methods: Helicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I-II) and moderate/severe atrophy (OLGA Stage III-IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains. Results: Among 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R. Conclusion: In treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen.
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PURPOSE: (1) To assess the clinical applicability of commercially available solutions for MR-based quantification of the hepatic fat fraction (HFF) and (2) to compare their results with clinically established in-phase/oppose-phase (IP/OP) imaging as proposed by Dixon. METHODS: Twenty-eight patients underwent MRI examinations using multigradient-echo sequences including multi-peak modeling and T2∗ correction, IP/OP imaging and multi-echo spectroscopy with successive HFF evaluation. Histopathological examination yielded the fraction of adipose hepatocytes (fAH) and the presence of increased liver iron concentration (LIC). We correlated HFF with fAH, and assessed concordance correlations among the MR-based methods with the presence of increased LIC as a control parameter. We investigated the liver segmentation quality and overall workflow of the postprocessing solutions (Philips LiverHealth and Siemens LiverLab). RESULTS: IP/OP imaging yielded a very strong correlation (r=0.88) with fAH when excluding three cases with increased LIC. Multigradient echo imaging and multiecho spectroscopy quantifications yielded similar correlations (r=0.87 0.93) as IP/OP imaging but were insensitive to increased LIC. Visceral fat, kidney tissue and major vessels were included regularly in the segmentation. Spectroscopic fat quantification was sensitive to the inclusion of visceral fat. CONCLUSIONS: IP/OP imaging allows HFF quantification when ruling out hepatic siderosis, whereas dedicated multi-echo imaging sequences and spectroscopy show no bias for increased iron concentration. The segmentation quality and workflow of both postprocessing solutions need to be improved. Nevertheless, all solutions are able to bring MRI-based hepatic fat quantification into the clinical application. We therefore recommend commercial hepatic fat quantification tools for institutions specialised to abdominal imaging.
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Hígado Graso , Tejido Adiposo/diagnóstico por imagen , Hígado Graso/diagnóstico por imagen , Hepatocitos , Humanos , Hígado/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Radiation-induced damage of the upper gastrointestinal (GI) tract results from radiation of GI tumors or structures adjacent to the GI tract. Radiation-induced damages of the upper GI tract may be acute or delayed, and ranges from lack of appetite, mucosal inflammation (i.e. esophagitis, gastritis, duodenitis) to ulcers, which may be complicated by perforation, penetration, bleeding and stenosis. Radiation-related factors as well as individual patient predisposing factors may increase susceptibility to post-radiation damage. High quality evidence for the treatment of radiation-induced GI damage is scarce and the management is often extrapolated from studies on GI lesions of different etiology. Treatment depends on severity and localization of the radiation-induced damage, and ranges from supportive and dietary measures to endoscopic interventions or surgery. Modern radiation techniques may decrease the incidence and severity of the radiation-induced upper gastrointestinal disease.
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Enfermedades Gastrointestinales , Tracto Gastrointestinal Superior/efectos de la radiación , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/terapia , HumanosRESUMEN
Neuronatin (NNAT) is a proteolipid involved in cation homeostasis especially in the developing brain. Its expression has been associated with the progression of lung cancer, glioblastoma, and neuroblastoma as well as glucose induced apoptosis in pancreatic cells. We performed a retrospective study of 148 breast cancer specimens for NNAT expression by immunohistochemistry to evaluate this protein as a prognostic marker for breast cancer. We found a high NNAT immunoreactivity score (by multivariate cox regression) to be an independent prognostic marker for relapse-free (hazard ratio HR = 3.55, p = 0.002) and overall survival (HR = 6.29, p < 0.001). However, NNAT expression was not associated with classical parameters such as hormone receptor expression (p = 0.86) or lymph node metastasis (p = 0.83). Additional independent risk factors in this study population were tumor size (≤2 cm; overall survival: HR = 0.36, p = 0.023; relapse-free survival: HR = 0.26, p < 0.01) and blood vessel infiltration (overall survival: HR = 0.34 p < 0.01). NNAT expression determined by immunohistochemistry might therefore become a helpful additional biomarker to identify high-risk breast cancer patients.