Salivary duct carcinoma cytologically diagnosed distinctly from salivary gland carcinomas with squamous differentiation

It has been difficult cytologically to distinguish salivary duct carcinoma (SDC) from high-grade carcinoma. We investigated the microscopic cytological findings, morphometric image analyses, and immunohistochemical features of SDC, focusing on how we achieved an accurate differential diagnosis distinguishing SDC from salivary gland carcinomas with squamous differentiation. Immunohistochemical staining was performed for androgen receptor (AR), gross cystic disease fluid protein-15 (GCDFP15), mammaglobin, human gastric mucin, MUC1, MUC2, p63, and cytokeratin high molecular weight. Of the 13 cases of SDC, 9 cases showed typical cytological findings of sheet clusters with polygonal granular cytoplasm with fine chromatin. The other 4 cases showed unusual cytological findings of a pseudo-papillary cluster or scattered cells only, and the tumor cells showed coarse chromatin. Morphometric image analysis showed that the nucleus area was statistically different between SDC and salivary gland carcinomas with squamous differentiation. AR-positive expression (P = 0.008), GCDFP15-positive expression (P = 0.005) and p63-negative expression (P = 0.001) were effective as SDC-specific markers in immunohistochemistry. An accurate cytological diagnosis of SDC can be determined by immunostaining with AR, GCDFP15, and p63, based on the nuclear findings.     

Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma

Twenty-one cases of primary lung carcinoma were analyzed for correlations between the presence of somatic mutations of the epidermal growth factor receptor (EGFR) gene and the phosphorylation status of EGFR, which was analyzed by immunohistochemistry with antibodies recognizing the phosphorylated form of EGFR. Somatic mutations were detected in 11 (52.4%) of the 21 cases. Immunohistochemistry with an antibody recognizing EGFR phosphorylated at tyrosine (pEGFR-tyr) 992 and an antibody recognizing EGFR phosphorylated at tyrosine 1173 (pEGFR-tyr1173) revealed that 12 (57.1%) and 21 (100%) of the 21 cases were positive, respectively. Interestingly, the mutation status of the EGFR gene was strongly correlated with immunoreactivity for pEGFR-tyr992 (P = .0019). pEGFR-tyr992 immunoreactivity was significantly correlated with clinical responsiveness to gefitinib (P = .0011). These findings suggest that immunohistochemical evaluation with anti-pEGFR-tyr992 antibody is useful for prediction of responsiveness to gefitinib.     

Peripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states

Ghrelin induces orexigenic behavior by activation of growth hormone secretagogue 1 receptors (GHSRs) in the ventral tegmental area (VTA) as well as hypothalamus, suggesting the involvement of mesolimbic dopamine system in the action of ghrelin. The present study aimed to identify neuronal mechanisms by which peripherally administered ghrelin regulates the mesolimbic dopamine system under different food-consumptive states. Ghrelin was administered to rats peripherally (3 nmol, i.v.) as well as locally into the VTA (0.3 nmol). Dopamine in the nucleus accumbens shell (NAc) was measured by microdialysis. Peripheral administration of ghrelin decreased dopamine levels in the NAc when food was removed following ghrelin administration. This inhibitory effect was mediated through GABA_A and N-methyl-d-aspartate (NMDA) receptors in the VTA. In contrast, when animals consumed food following ghrelin administration, dopamine levels increased robustly. This stimulatory effect was mediated through NMDA receptors, but not through GABA_A receptors, in the VTA. Importantly, both the inhibitory and stimulatory effects of ghrelin primarily required activation of GHSRs in the VTA. Furthermore, local injection of ghrelin into the VTA induced dopamine release in the NAc and food consumption, supporting the local action of ghrelin in the VTA. In conclusion, peripherally administered ghrelin activates GHSRs in the VTA, and induces bimodal effects on mesolimbic dopamine neurotransmission depending on food-consumptive states.     

The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n?=?44; gemcitabine?+?nab-paclitaxel [GnP], n?=?28; and gemcitabine?+?S-1 [GS], n?=?32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

     

Density of γ/δ+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age

Increased density of γ/δ T cell receptor (TCR)⁺ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial γ/δ and α/β TCR⁺ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial γ/δ T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of γ/δ⁺ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P< 0.0001). In controls, the density of γ/δ⁺ cells remained low throughout the age-range studies, from age 0.6–57 years. In controls, α/β⁺ cells increased with age (r = 0.57, P< 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.     

CD95 ligand is expressed in Reed–Sternberg cells of Hodgkin's disease

Reed-Sternberg (RS) cells and their mononuclear variants, Hodgkin's (H) cells, are considered to be the neoplastic cells of Hodgkin's disease (HD). The cellular origin of H-RS cells remains the subject of considerable controversy, although most recent papers have claimed that H-RS cells are of B cell origin. Recently, however, it has been reported that some H-RS cells express granzyme B, as observed in cytotoxic T cells and/or natural killer cells, which also express CD95 ligand (FasL/APO-1L). In the present study, the expression of CD95L and granzyme B in H-RS cells of HD was investigated. CD95L was detected in H-RS cells in five of nine HD cases (one case of lymphocyte-rich classical HD, two of these cases of nodular sclerosis type, and two of four cases of mixed cellularity type). All three examined HD cell lines expressed CD95L in the cytoplasm, although cell surface expression was seen only in L428 cells. Three HD cases expressed both CD95L and granzyme B. It was concluded that CD95L is frequently expressed in H-RS cells, which is one of their notable characteristics; albeit it seems to be irrespective of cell lineage.     

Visualization of the lower cranial nerves by 3D-FIESTA

MR cisternography has been introduced for use in neuroradiology. This method is capable of visualizing tiny structures such as blood vessels and cranial nerves in the cerebrospinal fluid (CSF) space because of its superior contrast resolution. The cranial nerves and small vessels are shown as structures of low intensity surrounded by marked hyperintensity of the CSF. In the present study, we evaluated visualization of the lower cranial nerves (glossopharyngeal, vagus, and accessory) by the three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA) sequence and multiplanar reformation (MPR) technique. The subjects were 8 men and 3 women, ranging in age from 21 to 76 years (average, 54 years). We examined the visualization of a total of 66 nerves in 11 subjects by 3D-FIESTA. The results were classified into four categories ranging from good visualization to non-visualization. In all cases, all glossopharyngeal and vagus nerves were identified to some extent, while accessory nerves were visualized either partially or entirely in only 16 cases. The total visualization rate was about 91%. In conclusion, 3D-FIESTA may be a useful method for visualization of the lower cranial nerves.     

High prevalence of acetabular retroversion in both affected and unaffected hips after Legg-Calvé-Perthes disease

Background

Acetabular retroversion is observed in hips after various pediatric hip diseases. This study sought to examine the frequency of acetabular retroversion in both affected and unaffected hips after Legg-Calvé-Perthes disease and its correlation with the prominence of the ischial spine.

Methods

We retrospectively investigated the version and morphological features of the acetabulum using pelvic radiographs after Legg-Calvé-Perthes disease (107 affected hips treated non-operatively and 72 unaffected hips from the contralateral side). The diagnosis of acetabular retroversion was made based on the presence of a positive cross-over sign on anteroposterior pelvic radiographs. The correlation between the presence of a positive cross-over sign and modified Stulberg classes, the onset age of Legg-Calvé-Perthes disease, radiographic parameters for acetabular dysplasia and the prominence of the ischial spine were examined.

Results

The prevalence of a positive cross-over sign was 49.5 % (45 of 91 hips) in affected hips and 45.8 % (33 of 72 hips) in unaffected hips. Hips with a positive cross-over sign were significantly coexistent bilaterally. The prevalence of prominence of the ischial spine in the positive cross-over sign group was 71.4 % in the affected side and 81.8 % in the unaffected side, indicating a significant correlation between the cross-over sign and the prominence of the ischial spine in both affected and unaffected hips. The positive cross-over sign did not have any correlation with the parameters for acetabular dysplasia and the onset age, however, had a significant correlation with the severity of the femoral head deformity.

Conclusions

High prevalence of acetabular retroversion in both affected and unaffected hips after Legg-Calvé-Perthes disease was demonstrated. Symmetric acetabular deformity and the coexistence of prominence of the ischial spine suggested the effects of the Legg-Calvé-Perthes disease lesions on the skeletal development of the whole pelvis. Further follow-up is needed to clarify the pathological significance of acetabular retroversion after Legg-Calvé-Perthes disease.     

Propofol Drip Infusion Anesthesia for MRI Scanning: Two Case Reports

The magnetic resonance imaging (MRI) room is a special environment. The required intense magnetic fields create unique problems with the use of standard anesthesia machines, syringe pumps, and physiologic monitors. We have recently experienced 2 oral maxillofacial surgery cases requiring MRI: a 15-year-old boy with developmental disability and a healthy 5-year-old boy. The patients required complete immobilization during the scanning for obtaining high-quality images for the best diagnosis. Anesthesia was started in the MRI scanning room. An endotracheal intubation was performed after induction with intravenous administration of muscle relaxant. Total intravenous anesthesia via propofol drip infusion (4–7 mg/kg/h) was used during the scanning. Standard physiologic monitors were used during scan pauses, but special monitors were used during scanning. In MRI scanning for oral maxillofacial surgery, general anesthesia, with the added advantage of having a secured airway, is recommended as a safe alternative to sedation especially in cases of patients with disability and precooperative chidren.Key Words: Magnetic resonance imaging (MRI), General anesthesia, Propofol drip infusion, Children, Developmental disability patientsThe magnetic resonance imaging (MRI) scanning room is a special environment. The required intense magnetic fields create unique problems with the usage of standard anesthesia machines, syringe pumps, and physiologic monitors (electrocardiogram, pulse oximeter, capnograph, and noninvasive blood pressure).^1–3 Moreover, the scanning procedure lasts around 1 hour. In addition, there is high-level acoustic noise in the MRI room. For the best quality of magnetic resonance imaging and diagnosis, complete immobilization of the patient is needed during scanning, often assisted by general anesthesia or sedation.³ However, special anesthesia instruments made of nonmagnetic materials needed for MRI scanning are not available at our university dental hospital.In this paper, we report 2 general anesthesia cases for MRI scanning in our dental hospital using alternative equipment.