Two-Day Fraction Gamma Knife Radiosurgery for Large Brain Metastasis.

Objective: We investigated how treating large brain metastasis (LBM) using two-day fraction gamma knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for two consecutive days, with a biologically effective dose (BED) equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods: Between November 2017 and December 2021, 42 patients (mean age: 68.3 years, range: 50-84 years, male: 29 [69.1%], female: 13 [30.9%]) with 44 tumors underwent two-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (NSCLC, N=16), small cell lung cancer (SCLC, N=7), colorectal cancer (N=7), breast cancer (N=3), gastric cancer (N=2), and other cancers (N=7). Twenty-one (50.0%) patients had a single LBM, nineteen (46.3%) had a single LBM and other metastasi(e)s, and two had two (4.7%) large brain metastases. At the time of the two-day fraction GKRS, the tumors had a mean volume of 23.1 cc (range: 12.5-67.4). on each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results: We obtained clinical and magnetic resonance imaging (MRI) follow-up data for 34 patients (81%) with 35 tumors, who had undergone two-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (P = 0.019) and lung cancer origin (P = 0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat SRS ranged from 15-878 days (median: 263±38 days, mean: 174±43) after the two-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion: Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

Spontaneous regression of colloid cyst on the third ventricle: a case report with the review of the literature.

BACKGROUND: Colloid cyst (CC) is a rare and benign cyst found in the third ventricle near the foramen of Monro. Although the role of surgical resection is well established in symptomatic large-sized CC, it remains debatable whether surgical removal of CC with no symptoms or minimal symptoms is necessary. CASE PRESENTATION: A 49-year-old male patient visited our institute for incidentally detected intracranial mass. MRI demonstrated typical, 12 mm-sized CC located in the third ventricle. It was noticed that the cyst spontaneously decreased in size from 12 mm to 4 mm on MRI at 18 months after the first visit. CONCLUSION: Although spontaneous regression is a very rare phenomenon in CC, regular imaging study and frequent neurologic examination can be an alternative option for well-selected, asymptomatic cases.

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs.

Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO2), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.

Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer.

PURPOSE: To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS: We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). RESULTS: With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. CONCLUSION: ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

Perforation of Surgical Gloves during Lower Extremity Fracture Surgery and Hip Joint Replacement Surgery.

PURPOSE: To assess the frequencies and sites of surgical glove perforations in lower extremity fracture surgery and hip joint replacement (HJR) surgery. Additionally, we also studied the usefulness of an indicator system glove. MATERIALS AND METHODS: We assessed surgical glove perforations in 30 cases of lower extremity fracture surgery and 18 cases of HJR surgery conducted by one right handed 1st operator from April 2013 to July 2013. We assessed frequencies and sites of perforation in 152 gloves; 95 used in lower extremity fracture surgery and 57 used in HJR surgery. We studied the perforation rates and sites according to participants and operation types. Using the Biogel indicator system glove, which is well known as a fast indicator of glove perforation, we were also able to assess the time difference between operative participant detection of perforation and inspector nurse detection while observing in the operative field. RESULTS: There were 18 of 30 cases in lower extremity fracture surgeries and 12 of 18 cases in HJR surgeries which had more than one surgical glove perforation event. Of all 152 gloves used, perforation occurred in 15 of 57 gloves (26.3%) in HJR surgery and 23 of 95 gloves (24.2%) in lower extremity fracture surgery. Perforation occurred more frequently in operators than assistant doctors or scrub nurses. The most frequent perforation site was the second digit of the left hand. On average, the time difference between operative participant notice of perforation and inspector nurse notice of perforation was 20.6 seconds. CONCLUSION: The perforation of surgical gloves happened in approximately one out of every four persons. Importantly, we noted a 37.0% prevalence of glove perforation in 1st operators. Considering that glove perforation is a critical factor responsible for intra-operative infection, surgeons must be conscious of the risk of surgical glove perforation and use double gloving regularly. Furthermore, indicator double gloving is recommended for fast detection of outer glove perforation.

The presence of fast-exchanging proton species in aqueous solutions of paraCEST agents can impact rate constants measured for slower exchanging species when fitting CEST spectra to the Bloch equations.

LnDOTA-tetraamide complexes typically exist in solution as a mixture of square-antiprismatic (SAP) and twisted square-antiprismatic (TSAP) coordination isomers. In most cases, the SAP isomer, which is preferred for CEST imaging, predominates, and the presence of the minor TSAP isomer is assumed to have little influence on quantitative measures of the water-exchange rate constant for the SAP isomer. Here, we sought to confirm the validity of this assumption by mixing two chelates with different SAP and TSAP isomer populations while measuring the water-exchange rate constant of the SAP isomer. The results show that an increase in the population of the TSAP isomer in solution results in as much as a 30% overestimation of the water-exchange rate constant for the SAP isomer when CEST spectra are fit to the Bloch equations. This effect was shown to be significant only when the TSAP isomer population exceeded 50%.

Results of Primary Total Hip Arthroplasty with 36-mm Femoral Heads on Highly Cross-linked Polyethylene-Minimum Seven-years Follow-up.

PURPOSE: We evaluate the clinical and radiographic midterm results of primary total hip arthroplasty (THA) using a 36 mm diameter femoral head on highly cross-linked polyethylene (minimum 7-year follow-up). MATERIALS AND METHODS: We retrospectively reviewed 73 patients (74 hips) that underwent primary THA with a 36 mm diameter femoral head on highly cross-linked polyethylene between July 2004 and February 2007. Clinical follow-ups included specific measurements like modified Harris hip scores (HHS) and Merle d'Aubigne and Postel score. For radiologic evaluations, together with position of acetabular cup at 6 weeks later of post-operation, we separately calculated the penentrations of femoral heads into polyethylene liners during post-operation and one year later check-ups, and during one year later check-ups and final check-ups. RESULTS: There were no complications except for one case of dislocation. Average modified HHS at final follow-up was 88±7.5 (range, 81-96), and Merle d'Aubigne and Postel scores were more than 15 (range, 15-18). Mean acetabular cup inclination and anteversion were 50.1°(range, 35°-58°) and 23.6°(range, 5°-38°), respectively. Average femoral head penetration during the first postoperative year was 0.071±0.034 mm/year, and steady-state wear rate determined using radiographs taken at one-year postoperatively and at latest follow-up was 0.051±0.022 mm/year. Average femoral head penetration during entire follow-ups was 0.058±0.013 mm/year. CONCLUSION: Primary THA with a large diameter femoral head on highly cross-linked polyethylene was found to produce the results comparable to previous in vitro laboratory hip simulation studies. And we also find out good scores in terms of patient's functionality.

Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy.

PURPOSE: For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer. MATERIALS AND METHODS: We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy). RESULTS: The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1). CONCLUSION: Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.

Phosphate-responsive promoter of a Pichia pastoris sodium phosphate symporter.

To develop a functional phosphate-regulated promoter in Pichia pastoris, a phosphate-responsive gene, PHO89, which encodes a putative sodium (Na(+))-coupled phosphate symporter, was isolated. Sequencing analyses revealed a 1,731-bp open reading frame encoding a 576-amino-acid polypeptide with 12 putative transmembrane domains. The properties of the PHO89 promoter (P(PHO89)) were investigated using a bacterial lipase gene as a reporter in 5-liter jar fermentation experiments. P(PHO89) was tightly regulated by phosphate and was highly activated when the cells were grown in a phosphate-limited external environment. Compared to translation elongation factor 1alpha and the glyceraldehyde-3-phosphate dehydrogenase promoter, P(PHO89) exhibited strong transcriptional activity with higher specific productivity (amount of lipase produced/cell/h). Furthermore, a cost-effective and simple P(PHO89)-based fermentation process was developed for industrial application. These results demonstrate the potential for efficient use of P(PHO89) for controlled production of recombinant proteins in P. pastoris.

Antiadhesive effect of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose after endoscopic sinus surgery.

BACKGROUND: We evaluated the clinical efficacy and safety of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HA-CMC) for prevention of adhesion after endoscopic sinus surgery. METHODS: Preoperative computed tomography (CT) scans were graded. At the completion of surgery, HA-CMC was applied to Merocel and repeatedly applied after the removal of Merocel. As a control, normal saline was applied. Endoscopic examination was performed postoperatively and grading was done. RESULTS: The rate of adhesion was the highest at 2 weeks postoperatively and was significantly lower in the HA-CMC-treated group than the control on all postoperative days. The grouping of cases by CT scores at 2 weeks postoperatively showed lower adhesion formation with the HA-CMC treatment than the control. The safety profile of the patients was normal at 4 weeks postoperatively. CONCLUSION: HA-CMC is an efficacious and safe material in decreasing the incidence of adhesion after endoscopic sinus surgery.

Expression of 15-lipoxygenase-1 in human nasal epithelium: its implication in mucociliary differentiation.

15-lipoxygenase-1 (15-LO-1) is involved in the differentiation of human tracheobronchial epithelial cells. Here, we investigated the relation between 15-LO-1 expression and the differentiation of human nasal epithelium. In retinoic acid (RA)-sufficient culture media, 15-LO-1 expression in normal human nasal epithelial cell time-dependently increased, but its expression was undetectable in RA-deficient culture media. Moreover, in RA-deficient culture media, IL-4 at 1 ng/ml concentration time-dependently induced 15-LO-1 expression. In addition, MUC8 gene expression, a marker of mucociliary differentiation, was up-regulated by 15-LO-1, which was itself induced by IL-4. In murine nasal mucosa, the expression of leukocyte type-12-LO, a functional equivalent of 15-LO-1, reduced after postnatal day 7. Our findings suggest that 15-LO-1 is related to the differentiation of human nasal epithelium, and that it may mediate the mucociliary differentiation of human nasal epithelium.

Ginkgo biloba extract (EGb 761) induces apoptosis by the activation of caspase-3 in oral cavity cancer cells.

We have investigated whether Ginkgo biloba extract (EGb 761) induces apoptosis of oral cavity cancer cells and attempted to characterize the apoptotic pathway activated by EGb 761. The inhibition of SCC 1483 oral cavity cancer cells proliferation was noted from 250 micro/ml of EGb 761. Apoptosis was observed after 24 h of incubation with 250 microg/ml EGb 761 and occurred in a time- and dose-dependent manner. Apoptosis was confirmed by DNA fragmentation and PARP cleavage. Co-treatment with the caspase inhibitor (z-VAD-fmk) inhibited apoptosis and PARP cleavage induced by EGb 761. Caspase-3 activity was upregulated by EGb 761 but reduced to the control level by co-treating with z-VAD-fmk. In summary, EGb 761 induces apoptosis of oral cavity cancer cells and caspase-3 is activated in this apoptosis. Therefore, EGb 761 may be considered as a possible chemopreventive agent against oral cavity cancer.

A case of solitary neurofibroma of the nasal dorsum: resection using an external rhinoplasty approach.

A 7-year-old girl had suffered from progressive swelling of the nasal dorsum over 2 years. Computed tomography and magnetic resonance imaging showed a large soft tissue density in the nasal dorsum. Tc-99m DTPA cisternography and brain SPECT showed a restricted mass in the nasal dorsum without intracranial connection. The mass was resected using an external rhinoplasty approach, and the pathologic diagnosis was of neurofibroma. Furthermore, the nasal dorsum was identified as the origin of the neurofibroma without the stigma of neurofibromatosis. Here, we present this case and discuss the clinical and pathological aspects of neurofibroma arising in the nasal dorsum.

Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene.

We have investigated whether NAG-1 is induced in oral cavity cancer cells by various NSAIDs and if apoptosis induced by NSAIDs can be linked directly with the induction of NAG-1. NAG-1 expression was increased by diclofenac, aceclofenac, indomethacin, ibuprofen, and sulindac sulfide, in the order of NAG-1 induction, but not by acetaminophen, piroxicam or NS-398. Diclofenac was the most effective NAG-1 inducer. Incubation with diclofenac inhibited cell proliferation and induced apoptosis. The expression of NAG-1 was observed in advance of the induction of apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila cells inhibited SCC 1483 cells proliferation and induced apoptosis. In summary, some NSAIDs induce NAG-1 expression in oral cavity cancer cells and the induced NAG-1 protein appears to mediate apoptosis. Therefore, NSAIDs may be considered as a possible chemopreventive agent against oral cavity cancer.