Fetal Cerebellar Growth Curves Based on Biomathematics in Normally Developing Japanese Fetuses and Fetuses with Trisomy 18

We used biomathematics to describe and compare cerebellar growth in normally developing and trisomy 18 Japanese fetuses. This retrospective study included 407 singleton pregnancies with fetuses at 14-39 weeks of gestation and 33 fetuses with trisomy 18 at 17-35 weeks. We used ultrasonography to measure fetal transverse cerebellar diameter (TCD) and anteroposterior cerebellar diameter (APCD). We hypothesized that cerebellar growth is proportional to cerebellar length at any given time point. We determined the formula L(t) ≒Keat+r, where e is Napier’s number, t is time, L is cerebellar length, and a, K, and r are constants. We then obtained regression functions for each TCD and APCD in all fetuses. The regression equations for TCD and APCD values in normal fetuses, expressed as exponential functions, were TCD(t)=27.85e0.02788t−28.62 (mm) (adjusted R2=0.997), and APCD(t)=324.29e0.00286t−322.62 (mm) (adjusted R2=0.995). These functions indicated that TCD and APCD grew at constant rates of 2.788%/week and 0.286%/week, respectively, throughout gestation. TCD (0.0153%/week) and APCD (0.000430%/week) grew more slowly in trisomy 18 fetuses. This study demonstrates the potential of biomathematics in clinical research and may aid in biological understanding of fetal cerebellar growth

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3–131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted

院内肺炎重症群（Ｃ群）に対するTazobactam/Piperacillin, Pazufloxacin 併用療法の有効性と安全性に関する検討

　院内肺炎重症群（Ｃ群）に対するTazobactam/Piperacillin（TAZ/PIPC），Pazufloxacin（PZFX）併用療法の有効性と安全性を検討した．院内肺炎重症群（C 群）20例を対象とし，TAZ/PIPC １回4.5g，１日３回， PZFX １回500mg，１日２回の併用投与を行い，その臨床効果，細菌学的効果，副作用などにつき検討した．その結果，臨床効果は，有効率60.0％（20例中12例有効）であった．細菌学的効果は，除菌率69.2％（13株中９株除菌）であり，Escherichia coli ３株中３株，Streptococcus pneumoniae ２株中２株，methicillin-sensitive Staphylococcus aureus ，Serratiamarcescense 各々１株中１株，Enterococcus faealis ，Pseudomonas aeruginosa 各々２株中１株が除菌された．副作用として，注射部位静脈炎が３例（15.0％）にみられ，臨床検査値の異常変動は８例（40.0％：肝機能障害４例，腎機能障害４例）にみられたが，いずれも軽度であった．以上より，TAZ/PIPC, PZFX 併用投与は，院内肺炎重症群（Ｃ群）に対して推奨できる治療法と考えられた．　The clinical effect and safety of Tazobactam/piperacillin and Pazufloxacin combination therapy on hospital-acquired pneumonia severe group (C group) was evaluated. Twenty patients were treated by combination of TAZ/PIPC (4.5g per dose, 3 times daily) and PZFX (500mg per dose, twice daily) .　Clinical effect, bacteriological effect, and adverse events were examined. Clinical efficacy rate was 60.0% (effectiveness in 12 of 20 patients). As for bacteriological effect, 3 of 3 Escherichia coli strais , 2 of 2 Streptococcus pneumoniae strains, 1 of 1 methicillin-sensitive Staphylococcus aureus strain and Serratia marcescense strain respectively, 1 of 2 Enterococcus faealis strains and Pseudomonas aeruginosa strains respectively were eradicated. In total, 9 (69.2%) of 13 strains were eradicated. Adverse events were infection site phlebitis in 3 patients (15.0%), and abnormal laboratory findings were observed including mild liver dysfunction in 4 patients and mild renal dysfunction in 4 patients. Consequently, TAZ/PIPC and PZFX combination therapy is recommended for hospital-acquired pneumonia severe group(C group)

Genomic Profiling of Submucosal-Invasive Gastric Cancer by Array-Based Comparative Genomic Hybridization

Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic

Carbon ion radiotherapy for desmoid tumor of the abdominal wall: a case report

The Erratum to this article has been published in World Journal of Surgical Oncology 2017 15:95[Background] Desmoid tumors, which are associated with familial adenomatous polyposis (FAP), tend to occur frequently in the abdominal wall and mesentery. Currently, there are no recognized treatments other than surgery, and frequent surgeries result in gastrointestinal obstructions and functional gastrointestinal disorders. [Case presentation] After surgery that was performed on a 39-year-old patient with FAP, we performed a second tumor excision which was the procedure used for frequently occurring mesenteric desmoid tumors. It was determined that the enlarged tumor would be difficult to operate on through an abdominal incision. Subsequently, the carbon ion radiotherapy of 50 Gy was then performed on the patient. Three years later, the tumor still remains reduced in size. In addition, we have not observed any negative effect on the digestive tract. [Conclusions] This is the first instance that the carbon ion radiotherapy has been effective for the unresected desmoid tumor, and it is believed that this will become the one effective option for the treatment of desmoid tumors

Recent advances in personalized lung cancer medicine

The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine