The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy

The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin-embedded tumor tissues. The median age was 65 years (range, 44-90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N-positive). Thirty-five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16-positive). Thirty-nine (83.0%) patients were positive for p16. After median follow-up of 51.7 months (range, 5.1-136.0 months), HPV16-positive group had significantly better 4-year progression-free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16-negative) group. Patients with p16-positive tumor also had a better 4-year PFS (52.5% vs. 25.0%, p = 0.014) than those with p16-negative tumor. In multivariate analysis for PFS, N-positive and HPV16-negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco-regional failure was statistically superior in HPV16-positive over HPV16-negative groups (p = 0.006), but time to systemic failure was not different (p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.     

Effect of particle size on the dissolution behaviors of poorly water-soluble drugs

This study examined the effects of the particle size of various poorly water-soluble drugs on their dissolution behavior through physicochemical and mathematical analysis. As model drugs, hydrochlorothiazide, aceclofenac, ibuprofen and a discovery candidate were selected. The materials were crystallized using an evaporation method and milled without transformation behavior of crystal forms. The particles were sieved and divided into four size groups (< 45 μm, 45～150 μm, 150～250 μm, and 250～600 μm). The specific surface area with regard to the particle size was measured using a BET surface area measurement. The specific surface area increased with decreasing particle size of the drug, resulting in an increase in dissolution rate. During the initial period of the dissolution study, significant differences in dissolution rate were observed according to the particle size and specific surface areas. On the other hand, in the later stages, the surface-specific dissolution rate was almost consistent regardless of the particle size. These observations were evaluated mathematically and the results suggested that the dissolution rate of poorly soluble drugs is strongly related to the particle size distribution. Moreover, physicochemical analysis helped explain the effect of particle size on the dissolution profiles.     

Comparative study of the uniformity of coating thickness of pellets coated with a conventional Wurster chamber and a swirl generator-equipped Wurster chamber

This study evaluated the performance of two bottom-spray coaters and the effect of pellet-size variability on coating uniformity. A conventional Wurster chamber was used for the first group of trials, and a Wurster chamber with a novel swirl-flow generator design was used for the second. The results confirmed that when using a conventional Wurster coating chamber, pellets with a smaller diameter receive significantly less coating material compared to those with larger diameters. The swirl generator-equipped Wurster chamber achieved close to uniform coating thickness regardless of pellet size. The ratio (M(S)) of the mass of dye deposited in the coating layer to pellet surface area indicates that coating was much more evenly distributed using the swirl-flow coater. Coating thickness was also analyzed using SEM micrographs and the results were in close agreement with the M(S) factor values. Inter-particle coating mass variation was also lower in case of swirl-flow coater. The results of this study show that a swirl-flow coater is suitable for coating particles of variable size. They also showed an improvement in coating process yield when using the swirl-flow coater.     

Development of enterohepatic fistula after embolization in ileal gastrointestinal stromal tumor: A case report

Gastrointestinal stromal tumor(GIST)is a rare mesenchymal tumor of the gastrointestinal tract that has been associated with the formation of fistulas to adjacent organs in few case reports.However,GIST with enterohepatic fistula has not been reported.Here we report the case of an enterohepatic fistula that occurred after embolization of a liver mass originating in the distal ileum.An 87-year-old woman was hospitalized for melena.On initial conventional endoscopy,a bleeding focus in the gastrointestinal tract was not found.Because of massive hematochezia,enteroscopy was performed through the anus.A protruding,ulcerative mass was found in the distal ileum that was suspected to be the source of the bleeding;a biopsy sample was taken.Electrocoagulation was not successful in controlling the bleeding;therefore,embolization was performed.After embolization,the patient developed a high fever and severe abdominal tenderness with rebound tenderness.Follow-up abdominopelvic computed tomography revealed an enterohepatic fistula between the liver and distal ileum.The fistula was treated surgically by segmental resection of the distal ileum and unlooping of the liver mass.     

Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats

OBJECTIVES: Expression of neuronal neuropeptides in inflammatory conditions is altered. The changes in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG) neurons were investigated by immunohistochemistry one week after unilateral ligature-induced periodontitis in rats. DESIGN: A retrograde nerve tracer Fluorogold (FG) was applied into the gingival sulcus of the second maxillary molar to identify the neurons in TG that specifically innervate the inflamed gingivomucosa. In addition, neurons from the corresponding maxillary and the adjacent mandibular-ophthalmic regions in TG were analysed. RESULTS: Statistically significantly higher frequencies of CGRP-positive neurons, regardless of their size, were found in TG ipsilateral to the periodontitis (83% and 73% in FG-labelled and maxillary regions, respectively) than in the control group without periodontitis (52% and 42% in FG-labelled and maxillary regions, respectively). The frequency of small FG-labelled SP-positive neurons in the ipsilateral TG (60%) was significantly higher than in the control TG (25%). In the contralateral TG the frequency of CGRP-positive neurons in maxillary region (66%) was significantly higher than in the control group. Surprisingly, the number of SP-positive neurons in all regions of contralateral TG decreased when compared to control and ipsilateral TGs. CONCLUSIONS: Taken together, these results implicate a role of neurogenic component in the pathogenesis of periodontitis. The contralateral response in the TG could be mediated through the transmedian neurological pathways crossing in the trigeminal nuclear complex or through the systemic inflammatory reaction and the activation of the so called "neuro-immune axis".     

Operative stabilization of the remaining mobile segment in ankylosed cervical spine in systemic onset- juvenile idiopathic arthritis:A case report

We describe a case of a 19-year-old young man with oligoarthritis type of juvenile idiopathic arthritis, who presented with several month duration of lower neck pain and progressive muscular weakness of all four limbs. X-rays of the cervical spine demonstrated spontaneous apophyseal joint fusion from the occipital condyle to C6 and from C7 to Th2 with marked instability between C6 and C7. Surgical intervention began with anterolateral approach to the cervical spine performing decompression, insertion of cage and anterior vertebral plate and screws, followed by posterior approach and fixation. Care was taken to restore sagittal balance. The condition was successfully operatively managed with multisegmental, both column fixation and fusion, resulting in pain cessation and resolution of myelopathy. Postoperatively, minor swallowing difficulties were noted, which ceased after three days. Patient was able to move around in a wheelchair on the sixth postoperative day. Stiff neck collar was advised for three months postoperatively with neck pain slowly decreasing in the course of first postoperative month.On the follow-up visit six months after the surgery patient exhibited no signs of spastic tetraparesis, X-rays of the cervical spine revealed solid bony fusion at single mobile segment C6-C7. He was able to gaze horizontally while sitting in a wheelchair. Signs of myelopathy with stiff neck and single movable segment raised concerns about intubation, but were successfully managed using awake fiber-optic intubation. Avoidance of tracheostomy enabled us to perform an anterolateral approach without increasing the risk of wound infection. Regarding surgical procedure, the same principles are obeyed as in management of fracture in ankylosing spondylitis or Mb. Forestrier.