Measurement of Trunk Movement during Sit-to-Stand Motion Using Laser Range Finders: A Preliminary Study.

The sit-to-stand (STS) motion evaluates physical functions in frail older adults. Mounting sensors or using a camera is necessary to measure trunk movement during STS motion. Therefore, we developed a simple measurement method by embedding laser range finders in the backrests and seats of chairs that can be used in daily life situations. The objective of this study was to validate the performance of the proposed measurement method in comparison with that of the optical motion capture (MoCap) system during STS motion. The STS motions of three healthy young adults were simultaneously measured under seven conditions using a chair with embedded sensors and the optical MoCap system. We evaluated the waveform similarity, absolute error, and relationship of the trunk joint angular excursions between these measurement methods. The experimental results indicated high waveform similarity in the trunk flexion phase regardless of STS conditions. Furthermore, a strong relationship was observed between the two measurement methods with respect to the angular excursion of the trunk flexion. Although the angular excursion of the trunk extension exhibited a large error, the developed chair with embedded sensors evaluated trunk flexion during the STS motion, which is a characteristic of frail older adults.

PP6 deficiency in mice with KRAS mutation and Trp53 loss promotes early death by PDAC with cachexia-like features.

To examine effects of PP6 gene (Ppp6c) deficiency on pancreatic tumor development, we developed pancreas-specific, tamoxifen-inducible Cre-mediated KP (KRAS(G12D) plus Trp53-deficient) mice (cKP mice) and crossed them with Ppp6cflox / flox mice. cKP mice with the homozygous Ppp6c deletion developed pancreatic tumors, became emaciated and required euthanasia within 150 days of mutation induction, phenotypes that were not seen in heterozygous or wild-type (WT) mice. At 30 days, a comparative analysis of genes commonly altered in homozygous versus WT Ppp6c cKP mice revealed enhanced activation of Erk and NFκB pathways in homozygotes. By 80 days, the number and size of tumors and number of precancerous lesions had significantly increased in the pancreas of Ppp6c homozygous relative to heterozygous or WT cKP mice. Ppp6c-/- tumors were pathologically diagnosed as pancreatic ductal adenocarcinoma (PDAC) undergoing the epithelial-mesenchymal transition (EMT), and cancer cells had invaded surrounding tissues in three out of six cases. Transcriptome and metabolome analyses indicated an enhanced cancer-specific glycolytic metabolism in Ppp6c-deficient cKP mice and the increased expression of inflammatory cytokines. Individual Ppp6c-/- cKP mice showed weight loss, decreased skeletal muscle and adipose tissue, and increased circulating tumor necrosis factor (TNF)-α and IL-6 levels, suggestive of systemic inflammation. Overall, Ppp6c deficiency in the presence of K-ras mutations and Trp53 gene deficiency promoted pancreatic tumorigenesis with generalized cachexia and early death. This study provided the first evidence that Ppp6c suppresses mouse pancreatic carcinogenesis and supports the use of Ppp6c-deficient cKP mice as a model for developing treatments for cachexia associated with pancreatic cancer.

Ppp6c deficiency accelerates K-rasG12D -induced tongue carcinogenesis.

BACKGROUND: Effective treatments for cancer harboring mutant RAS are lacking. In Drosophila, it was reported that PP6 suppresses tumorigenicity of mutant RAS. However, the information how PP6 regulates oncogenic RAS in mammals is limited. METHODS: We examined the effects of PP6 gene (Ppp6c) deficiency on tongue tumor development in K (K-rasG12D)- and KP (K-rasG12D + Trp53-deficient)-inducible mice. RESULTS: Mice of K and KP genotypes developed squamous cell carcinoma in situ in the tongue approximately 2 weeks after the induction of Ppp6c deficiency and was euthanized due to 20% loss of body weight. Transcriptome analysis revealed significantly different gene expressions between tissues of Ppp6c-deficient tongues and those of Ppp6c wild type, while Trp53 deficiency had a relatively smaller effect. We then analyzed genes commonly altered by Ppp6c deficiency, with or without Trp53 deficiency, and identified a group concentrated in KEGG database pathways defined as 'Pathways in Cancer' and 'Cytokine-cytokine receptor interaction'. We then evaluated signals downstream of oncogenic RAS and those regulated by PP6 substrates and found that in the presence of K-rasG12D, Ppp6c deletion enhanced the activation of the ERK-ELK1-FOS, AKT-4EBP1, and AKT-FOXO-CyclinD1 axes. Ppp6c deletion combined with K-rasG12D also enhanced DNA double-strand break (DSB) accumulation and activated NFκB signaling, upregulating IL-1ß, COX2, and TNF.

Ppp6c haploinsufficiency accelerates UV-induced BRAF(V600E)-initiated melanomagenesis.

According to TCGA database, mutations in PPP6C (encoding phosphatase PP6) are found in c. 10% of tumors from melanoma patients, in which they coexist with BRAF and NRAS mutations. To assess PP6 function in melanoma carcinogenesis, we generated mice in which we could specifically induce BRAF(V600E) expression and delete Ppp6c in melanocytes. In these mice, melanoma susceptibility following UVB irradiation exhibited the following pattern: Ppp6c semi-deficient (heterozygous) > Ppp6c wild-type > Ppp6c-deficient (homozygous) tumor types. Next-generation sequencing of Ppp6c heterozygous and wild-type melanoma tumors revealed that all harbored Trp53 mutations. However, Ppp6c heterozygous tumors showed a higher Signature 1 (mitotic/mitotic clock) mutation index compared with Ppp6c wild-type tumors, suggesting increased cell division. Analysis of cell lines derived from either Ppp6c heterozygous or wild-type melanoma tissues showed that both formed tumors in nude mice, but Ppp6c heterozygous tumors grew faster compared with those from the wild-type line. Ppp6c knockdown via siRNA in the Ppp6c heterozygous line promoted the accumulation of genomic damage and enhanced apoptosis relative to siRNA controls. We conclude that in the presence of BRAF(V600E) expression and UV-induced Trp53 mutation, Ppp6c haploinsufficiency promotes tumorigenesis.

Hypofractionated Radiotherapy for Anaplastic Thyroid Carcinoma: 15 Years of Experience in a Single Institution.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare cancer and has a poor prognosis. Several radiation protocols have been reported, but the results were not satisfactory. OBJECTIVE: The aim of this study was to determine the effect of hypofractionated radiotherapy. METHODS: Thirty-three patients who received radiotherapy for ATC between January 2000 and December 2014 were retrospectively included. We defined hypofractionated radiotherapy as a single dose ≥5 Gy. RESULTS: Nineteen patients were treated with hypofractionated radiotherapy. Twenty-eight patients died, and 27 of those patients died from ATC. Sixteen patients died from distant metastasis and 6 from local recurrence. In the hypofractionated radiotherapy group, local recurrence occurred in 5 patients and 1 of them died from active bleeding from a local tumor. There was local recurrence in 7 patients who received the other protocol, and 5 of them died from asphyxiation, active bleeding, or uncontrollable growth of a local tumor on the neck. The median overall survival (OS) was 5 months. In multivariate analysis, patients who received an equivalent dose in 2-Gy fractions (EQD2) ≥50 Gy had significantly better OS (p = 0.016). In univariate analysis, patients who received hypofractionated radiotherapy did not have significantly better OS (p = 0.872) or local control (p = 0.090). The χ2 test showed that significantly fewer patients died from local recurrence in the hypofractionated radiotherapy group (p = 0.025). CONCLUSIONS: Multivariate analysis showed that an EQD2 ≥50 Gy resulted in better OS, and hypofractionated radiotherapy decreased the rate of mortality from local recurrence.

Prognostic Impact of Renin-Angiotensin Inhibitors in Patients with Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Renin-angiotensin system blockade has been effective for the treatment of patients with several types of malignancy. This study evaluated the prognostic impact of renin-angiotensin system inhibitors, including angiotensin-2 converting enzyme inhibitors and angiotensin 2 receptor blockers, in patients with bladder cancer undergoing radical cystectomy. METHODS: This retrospective study included 269 patients who had undergone radical cystectomy. The oncologic outcomes of patients treated or not treated with renin-angiotensin system inhibitors after surgery were evaluated. Overall survival and cancer-specific survival were assessed by the Kaplan-Meier method and by Cox regression analysis. RESULTS: The median follow-up duration after radical cystectomy in survivors was 44.5 months. The 5-year, cancer-specific survival rates in patients who did and did not receive renin-angiotensin system inhibitors were 79.0 and 66.4 %, respectively (P = 0.011). Similarly, the 5-year overall survival rates were 76.1 and 61.4 %, respectively (P = 0.0097). Multivariable analyses showed that use of renin-angiotensin system inhibitors was an independent prognostic factor for cancer-specific survival (hazard ratio 0.47, P = 0.036) and for overall survival (hazard ratio 0.36, P = 0.022). CONCLUSIONS: Renin-angiotensin system inhibitors significantly reduced the risks of cancer-specific and overall mortality after radical cystectomy in patients with bladder cancer. Renin-angiotensin system inhibitors may improve oncologic outcomes in high-risk patients with bladder cancer.

Definitive Chemoradiotherapy for Advanced Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer with a poor prognosis. We herein report on a case of pulmonary sarcomatoid carcinoma that was treated successfully by concurrent chemoradiotherapy. A 65-year-old man was diagnosed to have pulmonary pleomorphic carcinoma (clinical T4N2M0 stage IIIB). He received concurrent chemoradiotherapy (60 Gy of radiotherapy in 30 fractionations and two courses of chemotherapy with carboplatin and paclitaxel). After chemoradiotherapy, a significant reduction of the tumor size was observed. Two courses of adjuvant chemotherapy were performed. He is currently alive at 15 months after the first treatment without any recurrence or metastasis.

Prognostic impact of perioperative lymphocyte-monocyte ratio in patients with bladder cancer undergoing radical cystectomy.

Various systemic inflammatory response biomarkers are associated with oncological outcome. We evaluated the superiority of prognostic predictive accuracy between neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR), and the prognostic significance of their perioperative change in patients with bladder cancer undergoing radical cystectomy (RC). We retrospectively analyzed 302 patients who had undergone RC in four institutions. Comparison of predictive accuracy between NLR and LMR was performed using receiver operating characteristic curve analysis. Overall survival (OS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method and Cox regression analysis. Preoperative and postoperative LMR showed higher predictive accuracy for OS than NLR did (p = 0.034). Applying a cutoff of 3.41, change in perioperative LMR stratified patients into three groups (low, intermediate, and high risk), showing a significant difference in OS and CSS (p < 0.001, each), and pathological outcomes. Multivariable analyses for OS and CSS showed that poor changes in LMR (high risk) were an independent prognostic factor (hazard ratio 5.70, 95 % confidence interval 3.49-9.32, p < 0.001; hazard ratio 4.53, 95 % confidence interval 2.63-7.82, p < 0.001; respectively). Perioperative LMR is significantly associated with survival in patients with bladder cancer after RC, and it is possibly superior to NLR as a prognostic factor.

Antimicrobial prophylaxis to prevent perioperative infection in urological surgery: a multicenter study.

We prospectively investigated the rates of incidence of surgical site infection (SSI), urinary tract infection (UTI), and remote infection (RI) in 4,677 patients who underwent urological surgery from January to December 2010, including 2,507 endourological cases, 1,276 clean cases, 807 clean-contaminated cases, and 87 contaminated cases involving bowel segments. A single dose of antimicrobial prophylaxis (AMP) was administered in the endourological, clean, and clean-contaminated surgery cases, except for patients who underwent transurethral resection of the prostate (TURP) or percutaneous nephrolithotripsy (PNL). AMP was administered within 72 h in TURP and PNL, and AMP was administered within 48 h in contaminated surgery cases. In cases of endourological surgery, UTI was observed in 4% and RI in 0%, and SSI, UTI, and RI were seen in 1%, 1%, and 1%, respectively, of clean surgery cases, in 3%, 3%, and 2%, respectively, of clean-contaminated surgery cases, and in 17%, 30%, and 10%, respectively, of contaminated surgery cases. In multivariate analysis of the risk factors for infection, operative time was a significant risk factor for UTI in endourological surgery, and American Society of Anesthesiologists score and operative time were significant risk factors for RI in clean surgery. No significant risk factor was found in analyses of clean-contaminated and contaminated surgery cases. A single-dose AMP regimen was shown to be effective and feasible for prevention of perioperative infection in urological surgery.

[A case of inflammatory myofibroblastic tumor of the urinary bladder].

A 61 year-old man complaining of asymptomatic gross hematuria was admitted to our hospital in May 2005. Transurethral resection of bladder tumor (TUR-BT) was performed for a bladder tumor (urothelial carcinoma (UC), pTa, G2). The TUR-BT was performed again because cystoscopy revealed a nonpapillary bladder tumor on the posterior bladder wall in September 2007. The pathological findings showed a UC, pTa, G2 and an inflammatory myofibroblastic tumor (IMT), pT1. The TUR-BT was performed two more times for tumor recurrences. We considered a total cystectomy because of the possibility of a pathologically low grade sarcoma and the considerable enlargement of the tumor size for a month after the TUR-BT. Ultimately, a malignant sarcoma was not diagnosed from the pathological findings. We practiced conservative therapy with a steroid and the tumor was reduced.

[An analysis of upper urinary tract recurrence following radical cystectomy for bladder cancer].

Transitional cell carcinoma of the urothelium is often multifocal, and subsequent tumors may occur anywhere in the urinary tract afer treating the initial carcinoma. The risk of an upper urinary tract recurrence following a radical cystectomy has been reported to be approximately 2 to 8%, but there are few reports with regard to the pattern and predictive factors of upper tract recurrence. We report here the incidence and pattern of upper tract recurrence following a radical cystectomy. Of the 166 patients 5 (3%) had upper tract recurrence. The prognosis of upper urinary tract recurrence is significantly better than other site of recurrence.

[Case with rupture of renal arterial aneurysm caused by fibromuscular dysplasia].

A 47-year-old women referred to our hospital with sudden left lower abdominal pain and state of shock in April 2006. Computed tomographic (CT) scan revealed a retroperitoneal hematoma and we suspected a renal tumor or angio myolipoma but enhanced CT scan show bleeding from a left renal artery. We perfomed left renal artery angiography and admitted a arteryal stenosis. Finally we diagnosed renal artery aneurysm caused by fibromuscular dysplasia. We performed left radical nephrectomy on the same day. We report the details of this case.