Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production

Background

Because of the rarity and variety of pancreatic neuroendocrine tumors (PNETs), there have been few reports regarding the indication for lymph node dissection in patients with these tumors. This study aimed to evaluate the risk of lymph node metastasis of PNETs based on the tumor size and hormonal production.

Methods

Data for a total of 66 patients who had PNETs resected at our department between 1987 and 2010 were retrospectively studied. The clinicopathological features, including the disease-specific survival rate, were assessed based on the status of lymph node metastasis at the time of initial surgical resection. Then the cut-off point of tumor size to predict lymph node metastasis was estimated.

Results

There were 12 patients (18%) with lymph node metastasis. The frequency of lymph node metastasis tended to be higher in gastrinomas than that in other tumors (43 vs. 15%; P?=?0.08). The size of PNETs with lymph node metastasis was significantly larger than that of the PNETs without metastasis (P?=?0.04). The postoperative survival rate in the PNET patients with lymph node metastasis was significantly lower than that in the patients without metastasis (P?Conclusions Non-gastrinomas with a tumor size of ≥15?mm and all gastrinomas would be an indication for pancreatectomy with lymph node dissection.     

The hematopoietic cell-specific Rho GTPase inhibitor ARHGDIB/D4GDI limits HIV type 1 replication

Rho GTPases are able to influence the replication of human immunodeficiency virus type 1 (HIV-1). However, little is known about the regulation of HIV-1 replication by guanine nucleotide dissociation inhibitors (GDIs), one of the three major regulators of the Rho GTPase activation cycle. From a T cell-based cDNA library screening, ARHGDIB/RhoGDIβ, a hematopoietic lineage-specific GDI family protein, was identified as a negative regulator of HIV-1 replication. Up-regulation of ARHGDIB attenuated the replication of HIV-1 in multiple T cell lines. The results showed that (1) a significant portion of RhoA and Rac1, but not Cdc42, exists in the GTP-bound active form under steady-state conditions, (2) ectopic ARHGDIB expression reduced the F-actin content and the active forms of both RhoA and Rac1, and (3) HIV-1 infection was attenuated by either ectopic expression of ARHGDIB or inhibition of the RhoA signal cascade at the HIV-1 Env-dependent early phase of the viral life cycle. This is in good agreement with the previous finding that RhoA and Rac1 promote HIV-1 entry by increasing the efficiency of receptor clustering and virus-cell membrane fusion. In conclusion, the ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions.     

Risk Factors of Local Oropharyngeal and Laryngeal Adverse Effects from Use of Single Inhaled Corticosteroids and Long-Acting Beta-Agonists

Background: Single inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) are clinically effective and safe. However, if local oropharyngeal and laryngeal adverse effects (LOLAE) appear, adherence to the use of ICS is impaired. To minimize the development of adverse effects, it is essential to identify the underlying risk factors.Methods: The study included 481 asthmatic patients who were prescribed ICS/LABA for the first time in their life between January and September of 2010. Patients ranged in age from 14 to 86 years old and consisted of 281 never smokers and 200 smokers. All data were collected retrospectively by respirologists.Results: Seventy-three out of 481 patients suffered from one or more adverse effects, with 54 of these exhibiting LOLAE. Patients with LOLAE (51.4 ± 16.2 yrs) were significantly older than those without LOLAE (43.7 ± 15.9 yrs) (p = 0.0011) and were also prescribed a significantly higher dose of ICS. The pack-years of patients with LOLAE (2.1 ± 4.9) were significantly lowerthan those without LOLAE (6.0 ± 13.0) (p = 0.0087). The type of administered ICS was also significantly associated with a risk of developing LOLAE.Conclusions: Our survey indicated that a greater age, a higher dose of ICS, and the type of ICS were potential risk factors of LOLAE. The identified factors should be considered in a clinical setting in order to prevent the development of LOLAE and provide optimal treatment to patients.     

Central visual field change after fornix-based trabeculectomy in Japanese normal-tension glaucoma patients managed under 15 mmHg

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate how the central visual field would be changed after fornix-based trabeculectomy with mitomycin C in Japanese...     

Detailed magnetic analysis and successful deep-neural-network-based conformational prediction for [VO(dmso)5][BPh4]2

Pentakis(dimethylsulfoxide-κO)oxidovanadium(iv) bis(tetraphenylborate), [VO(dmso)₅][BPh₄]₂ (dmso: dimethylsulfoxide), was synthesized, and its pseudo-C₄ VO₆ coordination geometry was revealed by a single-crystal X-ray method. A novel equation set was obtained for magnetic susceptibility and magnetization of the d¹ complexes, considering the axial distortion and the spin–orbit coupling for the ²D free-ion term. The equation set enabled magnetic simulation for significantly symmetry-lowered d¹ complexes to obtain the anisotropic g-values and also the excitation energies. In addition, conformational prediction was conducted, using the enumeration results on the basis of the group theory. The dominant conformers were predicted on the basis of the density functional theory (DFT) method, and especially, the conformer in the crystal was successfully predicted by a deep neural network method.

The conformer in the crystal was successfully predicted by a deep neural network method.     

Trial using pig cells with the H–D antigen knocked down

Purpose

This report describes an attempt to reduce the expression level of Hanganutziu–Deicher (H–D) antigens by small interfering RNA (siRNA) for pig cytidine monophospho-N-acetylneuraminic acid hydroxylase (pCMAH).

Methods

A pig endothelial cell (PEC) line, and PEC and fibroblasts from an α1,3galactosyltransferase knockout (GalT-KO) piglet were used. Real-time PCR was used to evaluate the degradation of mRNA by siRNA. The H–D antigen was stained, and then the cells were incubated with human serum for the FACS analysis. The extent of lysis in human serum was next calculated using an LDH assay.

Results

Suppression of the mRNA of pCMAH by each siRNA was first determined. The mixture of siRNAs for pCMAH reduced the expressions of the H–D antigen on the PEC and fibroblasts to a considerable extent. The further reduction in the xenoantigenicity for human serum of the GalT-KO cells was then confirmed. In addition, the PEC line showed a significant downregulation in complement-dependent cytotoxicity by the siRNAs, thus indicating that the anti-H–D antigen in human serum is capable of causing lysis of the pig cells.

Conclusion

pCMAH silencing by siRNA reduced the expression of the H–D antigen and its antigenicity, thus confirming that the H–D antigen is one of the major non-Gal antigens in this situation.     

Innervation pattern at the undersurface of the extensor carpi radialis brevis tendon in recalcitrant tennis elbow

Purpose

We investigated the general, sensory, and sympathetic innervation patterns at the undersurface of the extensor carpi radialis brevis (ECRB) origin in patients with recalcitrant tennis elbow.

Methods

Eight elbows in eight consecutive patients (6 females and 2 males) with tennis elbow who underwent arthroscopic surgery were included in this study. The mean age was 45 years (38–66 years), and the mean duration of symptoms before surgery was 23 months (13–52 months). Operative treatment consisted of an arthroscopic inspection and debridement of the ECRB origin. Control tissues were obtained from biopsy of the ECRB capsule in two patients with osteochondritis dissecance of the capitellum who underwent arthroscopic resection of loose bodies. The tissue specimens were investigated immunohistochemically with antibodies delineating general (PGP9.5), sensory (SP/CGRP), and sympathetic (NPY) nerve patterns.

Results

In the non-tendinosis control tissue, SP/CGRP and NPY immunoreactions were heterogeneously distributed in association with blood vessels. Pathologic evaluation of the biopsy tissue showed atypical fibrous granulation containing numerous vessels and nerve structures in all eight patients. Marked reactions to PGP 9.5 took the form of nerve fibers associated with arteries and arterioles in the atypical granulation. Most of the perivascular innervation was found to express NPY. The immunoreactions for SP and CGRP were invariably weak.

Conclusion

Increased perivascular sympathetic innervation accompanied with loss of sensory innervation at the undersurface of the ECRB tendon may play a role in chronic pain generation in recalcitrant tennis elbow.

Level of evidence

Diagnostic, Level IV.     

Clinicopathological Features of Recurrence in Patients After 10-year Disease-free Survival Following Curative Hepatic Resection of Hepatocellular Carcinoma

Background

The present study aimed to clarify the clinicopathologic features of long-term disease-fee survival after resection of hepatocellular carcinoma (HCC).

Methods

This retrospective study identified 940 patients who underwent curative resection of HCC between 1991 and 2000 at five university hospitals. Seventy-four patients with 10 years of recurrence-free survival were identified and followed up. They were divided into two groups, 60 recurrence-free and 14 with recurrence after a 10-year recurrence-free period.

Results

Overall survival rates of recurrence and non-recurrence groups were 68 and 91 % at 16 years, and 34 and 91 % at 20 years (p = 0.02), respectively. There were five (36 %), and two deaths (3 %), respectively, after 10 recurrence-free years. A second resection for recurrence was performed in four patients (29 %), and mean survival was 15.3 years after the first hepatectomy. Although three patients in the non-recurrence group (5 %) developed esophageal and/or gastric varices, seven patients in the recurrence group (50 %) developed varices during 10 years (p < 0.0001). In multivariate analysis, preoperative and 10-year platelet count was identified as a favorable independent factor for maintained recurrence-free survival after a 10-year recurrence-free period following curative hepatic resection of HCC.

Conclusions

Recurrence of HCC may occur even after a 10-year recurrence-free period. Long-term follow-up after resection of HCC is important, and should be life-long. Patients with higher preoperative and 10-year platelet counts are more likely to have long-term survival after resection. A low platelet count, related to the degree of liver fibrosis, is a risk factor for recurrence and survival of HCC after curative resection.     

Pyogenic discitis due to Abiotrophia adiacens

INTRODUCTIONAbiotrophia species have been referred to as nutritionally variant streptococci because of their fastidious nutritional requirements for growth. Abiotrophia species are difficult to identify with conventional solid culture.PRESENTATION OF CASEA 48-year-old woman was admitted to our hospital with severe low back pain and body temperature of 38.2 °C. Magnetic resonance imaging revealed edema and contrast enhancement of the L4 and L5 vertebral bodies with high signal intensity in the L3-4 and L4-5 intervertebral discs on the T2-weighted images. The patient underwent needle biopsy of the L3-4 disk. Cultures of disk biopsy samples and blood yielded gram positive cocci in short chains with scanty growth on chocolate agar. Further subculture with supplemented medium and subsequent 16S ribosomal RNA gene sequencing identified the pathogen as Abiotrhophia adiacens. The patient was treated with intravenous ampicillin. At 6-month follow-up, the patient was free of symptoms.DISCUSSIONCausative microorganisms remain unidentified in 25–40% of spinal infection cases. Abiotrophia species grow poorly on conventional solid media, and require pyridoxal or thiol group supplementation. Use of Brucella HK agar or GAM agar plate is helpful for detection of Abiotrophia species. We first confirmed the diagnosis by direct identification of Abiotrophia adiacens from infected disk. Abiotrophia species are one of the major pathogens of infective endocarditis accounting for 5% of cases. Considering their fastidious nature, it is likely that most cases of Abiotrophia discitis are falsely classified as culture-negative discitis; therefore, their role in pyogenic discitis may be underestimated.CONCLUSIONSubculture using nutritionally supplemented media is crucial for their identification.     

Effect of loading conditions on the fracture toughness of zirconia

PurposeA Vickers hardness indenter was pressed into yttria-stabilized zirconia (Y-TZP) by the indentation fracture method (IF method).MethodsThe effect on the calculated Vickers hardness, fracture toughness values, and indentation fracture load (9.8, 49, 98, 196, and 294 N) was examined to deduce the optimum conditions of the IF method. Calculated Vickers hardness and fracture toughness values were analyzed with one-way analysis of variance and then multiple comparisons (Scheffe). The appearance of on indentation and cracks was also evaluated using a scanning electron microscopy (SEM).ResultsIndentation of Y-TZP was generated by 9.8 and 49 N of indentation fracture load, however cracks could not be confirmed with the microscope attached to the Vickers hardness tester. Both indentation and cracks were observed at 98, 196 and 294 N of indentation fracture load obtained values of 7.1 and 6.8 MPam^1/2. Cracks noted at the 98 N were not clear, whereas the 196 and 294 N showed especially clear cracks. Due to the hardness of zirconia and the light loads, fracture toughness values for 9.8, 49, and 98 N could not be calculated. There was no significant difference between 196 and 294 N, when calculated fracture toughness values were analyzed with multiple comparisons. SEM revealed clear indentation and cracks, that extended linearly, but no chips or fractures were observed. Surface changes were observed at 196 and 294 N that are presumed to be accompanied by phase transition around the cracks.ConclusionsOptimum experimental conditions of the indentation fracture load in the IF method were determined as 196 and 294 N.