Massive osteolysis in a girl with agenesis of thyroid C cells

A rare case of massive osteolysis affecting the pelvis of a young girl is presented. The clinical, radiographic, and histopathological features are described in detail. Septicemia complicated the clinical course and the patient eventually died. Histopathological examination of the pelvic lesion revealed massive osteolysis characterized by prominent osteoclastic activity with extensive bone resorption. A thorough post-mortem histological examination of the thyroid gland showed no C cells. This is an interesting observation, since it is known that thyroid C cells are the primary source of calcitonin. Since the main biological effect of calcitonin is to inhibit osteoclastic bone resorption, there is a possibility that massive osteolysis in our case could have been related to the lack of this hormone. There is a clear need for further investigation regarding the role of thyroid C cells and calcitonin in this puzzling disease.     

Duplicated muscularis mucosae invasion has similar risk of lymph node metastasis and recurrence-free survival as intramucosal esophageal adenocarcinoma

Duplicated muscularis mucosae (MM) in early esophageal adenocarcinoma (EAC) can cause overstaging of the disease on endoscopic ultrasound and pathology specimens. No study has determined the correlation between lymph node metastasis and invasion in the space between duplicated MM in pathologic tumor stage (pT) 1 EAC. Hematoxylin and eosin-stained slides from surgically resected pT1 EAC (n=99) were reviewed for tumor configuration, grade, level of invasion (lamina propria/inner MM, space between duplicated MM, and submucosa), quantitative depth of invasion in millimeter, and lymphovascular invasion (LVI). These pathologic characteristics were correlated with lymph node status and recurrence-free survival (RFS). All specimens had duplicated MM with thick-walled blood vessels. Tumor differentiation was well in 37, moderate in 47, and poor in 15 specimens. EAC invaded the lamina propria/inner MM in 28 cases, duplicated MM space in 41 cases, and submucosa in 30 cases. LVI was identified in 23 tumors. Eleven patients had lymph node metastasis. Quantitative depth of invasion as a continuous variable (P=0.002), poorly differentiated histology (P=0.028), presence of LVI (P=0.001), and submucosal invasion versus duplicated MM/lamina propria invasion (P=0.02) were associated with increased risk of lymph node metastasis and shorter RFS by univariate analysis. By multivariate analysis, LVI was an independent predictor of lymph node status and RFS. EAC invasion into the space between duplicated MM confers a similar risk of lymph node metastasis and recurrence as those of intramucosal EAC, and LVI is the best predictor of lymph node status and RFS in pT1 EAC.     

Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia

Background: The association between celiac disease (CD) and type 1 diabetes mellitus (T1DM) is well known. Up to now, CD prevalence in children and adolescents with T1DM in Serbia has not been reported. The aim of the present study was to determine CD prevalence and its clinical manifestations in patients with T1DM. Methods: One hundred and twenty‐one patients (70 girls, 51 boys; mean age, 10.8 years) with T1DM (mean duration of diabetes, 3.4 years) and 125 control group participants (75 girls, 50 boys; mean age, 10.4 years) were tested for CD on tissue transglutaminase antibodies (tTG). In seven serologically positive T1DM patients endoscopic small bowel biopsies were taken and examined on histopathology. In all patients with CD and T1DM age, duration of T1DM, height for age, body mass index, glycosylated hemoglobin and clinical symptoms were noted. Results: Nine patients with T1DM were positive on IgA tTG antibodies. In seven of them small bowel biopsy was performed, and all were proven to have CD on histopathology. The prevalence of biopsy‐proven CD in children and adolescents with T1DM was significantly higher in the study group compared to controls (5.79%. vs 0.8%, P < 0.05). Conclusion: The significantly higher prevalence of CD in children with type 1 diabetes, in accordance with the large volume of data published in the literature, underlines the need for yearly screening of CD in patients with diabetes in order to promptly start a gluten‐free diet when appropriate.     

Therapy-induced expression of NF-κB portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation

Activated nuclear factor‐kappa B (NF‐κB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF‐κB prior to any therapy portends poor prognosis, and it is also known that activated NF‐κB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment‐induced activation of NF‐κB (meaning their cancers activate NF‐κB during or after therapy) is not been reported. We hypothesized that the treatment‐induced activation of NF‐κB would impart poor prognosis similar to that imparted by constitutively activated NF‐κB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre‐ and post‐therapy cancer tissue available were selected. Pre‐ and post‐therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF‐κB. The overall survival (OS) and disease‐free survival were assessed and compared for patients who had intrinsic constitutively activated NF‐κB cancer with those who had induced activation of NF‐κB only post‐therapy. A total of 41 patients with LEA were investigated. Twenty‐five patients had NF‐κB positive cancer at baseline, and 16 had NF‐κB negative cancer at baseline but became positive post‐therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease‐free survival (P = 0.86), and median survivals (Converters: 24 months [95% confidence intervals: 7.78 to 40.22]vs. Nonconverters: 34.13 months [95% confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF‐κB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre‐therapy evaluation of NF‐κB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti‐NF‐κB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF‐κB or cancer may have to be monitored during therapy with biomarker assessments.