Prediction of pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography.

AIM: To determine whether the pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) can be predicted using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (F-18 FDG-PET). MATERIALS AND METHODS: Twenty-eight patients with PDAC who underwent only neoadjuvant chemotherapy (NAC) before surgery were enrolled in the study. All patients had F-18 FDG-PET examinations before NAC. The resected specimen was pathologically evaluated according to the Classification of Pancreatic Carcinoma (7th edn). Patients were categorised into a non-response group and a response group based on the pathological findings. The non-response group (Grades 1a and 1b) showed ≤50% necrosis in the specimen, while the specimens of the response group (Grades 2-3) showed >50% necrosis. The maximum standardised uptake values (SUVmax) of the tumours on F-18 FDG-PET were measured. The mean values of SUVmax were compared between the two groups. The diagnostic performance of SUVmax in distinguishing the two groups was also evaluated using receiver operating characteristic analysis. RESULTS: The mean SUVmax of the response group was higher than that of the non-response group (9.00 ± 1.78 versus 4.26 ± 2.35; p<0.001). The optimal cut-off value of SUVmax was 9.28 for distinguishing the two groups. The sensitivity, specificity, and accuracy for the prediction in the response group were 80%, 95.7%, and 92.9%, respectively. CONCLUSIONS: SUVmax on F-18 FDG-PET may be useful as a biomarker to predict the pathological response to NAC in patients with PDAC.

Remarkable Improvement of Cardiac Function After Pre-emptive Kidney Transplant in a Patient With Severe Mitral Regurgitation Accompanied by Low Cardiac Function: A Case Report.

Patients with end-stage renal disease are at a high risk for cardiovascular diseases. It is controversial whether end-stage renal disease patients with low cardiac function can safely accept kidney transplant. Here, we present a 42-year-old kidney transplant recipient with severe mitral regurgitation accompanied by low cardiac function. He wanted to undergo a pre-emptive kidney transplant from his uncle. We decided to perform living kidney transplant prior to cardiac surgery. Despite adequate ultrafiltration and hemodiafiltration before operation, the patient's ejection fraction still remained 35% 1 day before transplant. He showed complete recovery of cardiac function in only 2 days after pre-emptive kidney transplant, although his body weight did not change before and after the operation. Early removal of the uremic toxin or inflammatory cytokines may play a role in rapid improvement of the cardiac function. Increase of vasoactive substances by improvement of kidney function may lead to reduction of afterload and amelioration of cardiac microcirculation. This report also suggests that optimal timing for operation might be important.

Relationships among maxillofacial morphologies, bone properties, and bone metabolic markers in patients with jaw deformities.

The aim of this study was to determine the relationships among bone properties, bone metabolic markers, and types of jaw deformity. The subjects were 55 female patients with jaw deformities. Skeletal morphology was examined using lateral cephalograms, and the patients were divided into three groups according to the type of anteroposterior skeletal pattern. Serum osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b, as well as deoxypyridinoline in urine, were measured as bone metabolic markers. Quantitative ultrasound (QUS) measurements were used to assess bone properties at the calcaneal bone. The bone volume and bone density of the condylar process were measured in 43 patients by computed tomography. There were no significant differences in bone metabolic markers and QUS parameters between the groups, although bone formation and resorption markers tended to be higher in patients with a protrusive mandible. On the other hand, patients with mandibular retrusion had a higher tendency to have small and dense condylar processes. In conclusion, the results suggest that growth depression or a degenerative change in the mandibular condyle is involved in the pathogenesis of mandibular retrusion, although risk factors for progressive condylar resorption were not determined.

Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis.

OBJECTIVES: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA. METHOD: OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and LOX-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression. RESULTS: In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX-1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression. CONCLUSIONS: These data indicate that the LOX-1/ox-LDL system plays a pivotal role in the pathogenesis of instability-induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte-forming cells may be possible targets to prevent disease progression in OA.

MR Imaging Findings of a Leiomyosarcoma of the Thoracic Spine: A Case Report.

We report a case of leiomyosarcoma of the thoracic spine. Primary leiomyosarcoma is a malignant connective tissue tumor originating from smooth muscle cells. Leiomyosarcoma frequently occurs in the uterus, retroperitoneal space, gastrointestinal tract, and deep soft tissues; primary leiomyosarcoma of the bone is rare. The MR imaging including intravoxel incoherent motion (IVIM) imaging findings of the current case indicated a low diffusion coefficient and high blood flow, which were in concurrence with high cell density on histology and increased vascularity by angiography. Although some benign tumors such as osteoblastoma and giant cell tumor would show similar findings on IVIM imaging, these additional imaging features may narrow the differential diagnosis of spinal tumors.

Identification and analysis of CXCR4-positive synovial sarcoma-initiating cells.

Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro. The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity than negative ones and possessed both self-renewal and multipotent differentiation ability. Immunohistochemical analysis of 39 specimens of synovial sarcoma patients revealed that CXCR4 strongly correlated with poor prognosis of synovial sarcoma. Thus, we conclude that CXCR4 is the marker of synovial sarcoma-initiating cells, a new biomarker for prognosis and a new potential therapeutic target.

Laparoscopic en bloc excision of gastrointestinal stromal tumors of the rectum after neoadjuvant imatinib therapy: anteriorly extended intersphincteric resection combined with partial resection of the prostate.

We herein present a novel technique for laparoscopic en bloc excision involving anteriorly extended intersphincteric resection with partial resection of the posterior lobe of the prostate for large rectal gastrointestinal stromal tumors (GISTs). The sequence of neoadjuvant imatinib therapy and this less invasive surgery for marginally resectable rectal GISTs has the potential to obviate the need for urinary reconstruction and permanent stomas without jeopardizing the tumor margin status.

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey.

PURPOSE: Intestinal neuronal dysplasia Type B (IND-B) has been proposed to be an allied disorder of Hirschsprung's disease (ADHD). The original histological criteria included hyperganglionosis, giant ganglia, ectopic ganglion cells and an increased AChE activity in the lamina propria. The criteria for IND-B have been gradually revised. The present diagnostic criteria are [1] more than 20 % of the submucosal ganglia contain nine or more ganglion cells and [2] the patient is older than 1 year. To clarify the current status of IND-B in Japan, a nationwide retrospective cohort study was performed. METHODS: Questionnaires were sent to 161 major institutes of pediatric surgery and gastroenterology in Japan. RESULTS: A total of 355 cases of ADHD were collected, including 18 cases of IND-B (5 %). Based on original criteria, 13 out of 18 cases were diagnosed as IND-B. However, only four cases met the current criteria. Three of the four patients (75 %) required pull-through operation. All of the patients exhibited giant ganglia and ganglioneuromatosis-like hyperplasia of the myenteric plexus. CONCLUSIONS: IND-B cases matching the current criteria are thought to be quite rare and they are associated with marked hyperplasia of the myenteric plexus. "True" IND-B is a rare and intractable disease.

Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living-donor liver transplantation for primary biliary cirrhosis.

INTRODUCTION: Few studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Fifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed. RESULTS: The 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥ 4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from "chronic immune-mediated reaction syndrome," showed reciprocal changes over time. No patient died of recurrent PBC. CONCLUSIONS: Male donor and ≥ 4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC.

Factors affecting variability in home blood pressure in patients with type 2 diabetes: post hoc analysis of a cross-sectional multicenter study.

Recent studies have shown that variability in home blood pressure has an important role in the progression of organ damage. The objective of this study was to investigate the factors that affect variability in home blood pressure in patients with type 2 diabetes. We assessed the relationship between home blood pressure variability, defined as coefficient of variation of mean of triplicate morning and evening blood pressure for 14 consecutive days, and various factors using univariate and multivariate linear regression analyses in 1114 patients with type 2 diabetes. Age (ß=0.149, P<0.001), female sex (ß=0.125, P=0.010), duration of diabetes mellitus (ß=0.103, P=0.005), heart rate (ß=0.136, P<0.001), current smoker (ß=0.118, P=0.005), white-coat hypertension (ß=0.136, P=0.002) and treatment with calcium channel blockers (ß=-0.094, P=0.024) were independently associated with coefficient of variation of morning systolic blood pressure. Our findings implicate that factors that might be intervened such as heart rate, smoking status, use of antihypertensive medication in addition to age, sex and duration of diabetes mellitus are associated with variability in home blood pressure in patients with type 2 diabetes.

Oxidative DNA damage in human esophageal cancer: clinicopathological analysis of 8-hydroxydeoxyguanosine and its repair enzyme.

Both internal and external oxidative stresses act on DNA and can induce carcinogenesis. 8-hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and it leads to transversion mutations and carcinogenesis. 8-OHdG is excision-repaired by 8-OHdG DNA glycosylase (OGG1). The purpose of this study is to clarify the effect of oxidative DNA damage and repair enzymes on esophageal carcinogenesis. The levels of 8-OHdG and OGG1 were immunohistochemically evaluated in resected specimens, including squamous cell carcinoma (SCC) in 97 patients with esophageal cancer. Higher levels of 8-OHdG in normal esophageal epithelium were associated with a higher smoking index (P = 0.0464). The 8-OHdG level was higher in cancerous areas than in normal epithelia (P = 0.0061), whereas OGG1 expression was weaker in cancerous areas than in normal epithelia (P < 0.0001). An increase of OGG1 expression in normal epithelium was observed as 8-OHdG levels increased (P = 0.0011). However, this correlation was not observed in cancerous areas. High OGG1 expression in the cytoplasm was related to deeper tumors (P = 0.0023), node metastasis (P = 0.0065) and stage (P = 0.0019). Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis and its progression.

Endometrial metaplasia: correlation of histological and cytological specimens obtained from 103 cases undergoing hysterectomy for endometrial carcinoma.

OBJECTIVE: To assess the frequency of endometrial metaplasia in histological and cytological specimens from the same cases, and to determine the relationship between various types of metaplasia and clinicopathological findings. METHODS: We reviewed 103 histological specimens diagnosed as endometrioid adenocarcinoma, in which endometrial smears had been obtained before surgery. We examined the correlation between the frequency of endometrial metaplasia occurring in association with carcinoma in both histological and cytological specimens. The categories of metaplasia were eosinophilic metaplasia, squamous metaplasia, mucinous metaplasia, ciliated cell metaplasia and others. We compared the incidence of endometrial metaplasia with the clinicopathological findings for each case. RESULTS: Endometrial metaplasia was recognized in 90 (87.4%) of the histological and 80 (77.7%) of the cytological specimens of 103 specimens, with the respective frequency of subtypes as follows: eosinophilic metaplasia (36.0% and 43.7%), squamous metaplasia (70.9% and 68.0%), mucinous metaplasia (38.8% and 19.4%), ciliated cell metaplasia (22.3% and 2.9%) and others (11.7% and 0%). Mixed subtypes were seen in 58.3% and 41.7% of histological and cytological specimens, respectively. In histology, mucinous metaplasia was significantly more frequent in G1-G2 than G3 carcinomas (P = 0.0089). Ciliated cell metaplasia was significantly related to endometrial hyperplasia (P = 0.0068). In cytology, eosinophilic and mucinous metaplasia were significantly associated with G1-G2 cases (P = 0.0061 and P = 0.0385). CONCLUSIONS: Endometrial metaplasia was seen in 87.4% of the histological and 77.7% of the cytological specimens. Where routine endometrial cytopathology is practiced, it is important to understand the detailed histological and cytological features of these changes.

Evaluating the association between histological manifestations of cord colitis syndrome with GVHD.

Cord colitis syndrome (CCS) is a recently proposed clinical entity characterized by a persistent diarrheal illness after cord blood transplantation (CBT), which is not caused by GVHD or CMV colitis. CCS is histologically characterized by chronic active colitis with granulomatous inflammation and Paneth cell metaplasia suggesting chronicity. However, the specificity of these pathological features to CCS remains to be validated. We conducted a retrospective study of 49 patients who had diarrhea and underwent diagnostic colonoscopy with biopsy following allogeneic hematopoietic SCT. None of the patients met the clinical criteria for CCS. Chronic active colitis with granulomatous inflammation and Paneth cell metaplasia was present in 12/33 (36%) patients with biopsy-proven GVHD, 4/6 (67%) patients with CMV colitis and 2/15 (13%) patients with nonspecific colitis. In patients with GVHD and/or CMV colitis, these pathological features were present in 4/8 (50%) patients after CBT and in 11/26 (42%) patients undergoing BMT or PBSCT. These results demonstrate that chronic active colitis with granuloma and Paneth cell metaplasia is not only a specific feature of CCS but also is present in GVHD and CMV colitis, irrespective of stem cell source.

Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.

Evaluation of bone volume changes after sinus floor augmentation with autogenous bone grafts.

The aim of this study was to establish an objective method for quantitative evaluation of bone volume change after sinus augmentation. 11 sinuses in 9 patients were evaluated by computed tomography images taken before treatment (T0), and 3 months (T1) and at least 1 year (T2) after sinus augmentation. Based on the 3D digital subtraction technique, augmented bone images were extracted and bone volumes were calculated from voxel numbers of the extracted images. The mean augmented bone volumes at T1 and T2 were 2.46 cm3 and 1.85 cm3, respectively. These bone volume changes were statistically significant and the mean bone volume change ± SE was -24.8% ± 6.1%. Loss of augmented bone was observed in all except one of the patients. The correlation coefficient between bone volume change and elapsed time was -0.64, which was statistically significant and indicated that bone resorption progressed with elapse of time after sinus augmentation. The authors' method of analysis enabled visualization of augmented bone and objective assessment of bone volume change. Within the limited number of cases, the present investigation demonstrated a significant decrease in augmented bone volume between 3 and 23 months after surgery.

[Staged carotid artery stent and cardiac surgery under cardiopulmonary bypass].

The presence of carotid disease in patients undergoing cardiac surgery has been known to increase the risk of peri-operative strokes. However, there are some controversies surrounding carotid artery stenting (CAS) in patients undergoing cardiac surgery with carotid disease. We experienced 5 cases of staged carotid artery stent and cardiac surgery under cardiopulmonary bypass. These cases represent 1.7% of the cardiac surgery between August 2006 and June 2009 at our hospital. There were 4 male and 1 female patient whose ages range from 58 to 81 years old (mean 73.0). Two cases were symptomatic and revealed carotid artery stenosis of 50% or more. The remaining 3 asymptomatic cases had 75% or more stenosis. Wallstent RP stents were used in 3 of the cases, and PRECISE stents in the remaining 2. The mean time of carotid angioplasty and stenting was 101 ± 22 minutes. Among the 5 cases, we experienced 2 periprocedural events. One developed bradycardia and cardiac arrest due to severe aortic valve stenosis, which was promptly improved by temporary cardiac pacing. The other experienced transient hemiparesis. The mean period of time between CAS and cardiac surgery was 53 days, with a range of 23 to 78 days. There were no post-operative deaths or strokes. All 5 cardiac operations were performed successfully. Further cooperation among cardiologists, cardiac surgeons and neurosurgeons is suggested for more careful circulatory assessment during CAS in patients with severe cardiac disease.

The lingual lymph node identified as a sentinel node on CT lymphography in a patient with cN0 squamous cell carcinoma of the tongue.

We performed CT lymphography on an 81-year-old female patient with a histologically confirmed squamous cell carcinoma of the tongue with no clinical or radiological evidence of cervical lymph node involvement. The lateral lingual lymph node was identified as a sentinel node, which is the first lymph node to receive drainage from a primary tumour. CT lymphography also showed draining lymphatics passing through the sublingual space, the medial side of the submandibular gland and near the hyoid bone and connected with the middle internal jugular node. Although metastasis to the lateral lingual lymph node is known as one of the crucial events in determining survival outcome in cancer of the tongue and floor of the mouth, very few reports are available on the imaging of the lateral lingual lymph node metastasis. This is the first report regarding the lateral lingual lymph node identified as a sentinel node demonstrated on CT lymphography.

Stromal expression of cathepsin K in squamous cell carcinoma.

BACKGROUND: Cathepsin K (CTSK), a cysteine protease with strong collagenolytic and elastolytic properties involved in extracellular matrix turnover, may be produced by neoplastic cells as well as stromal macrophages and fibroblasts. Its expression is suggested as associated with increased invasive and metastatic potential. OBJECTIVES: The aim of this study is to examine stromal expression of cathepsin K in skin tumors. METHODS: A series of 13 normal skin and 109 skin tumours, including 51 benign and 58 malignant epidermal tumours were tested for CTSK and Ki-67 expression by immunohistochemical analysis. RESULTS: Stromal CTSK expression and the tumoral Ki-67 labelling index were significantly higher in invasive squamous cell carcinoma (SCC) than in other epidermal tumours. CONCLUSION: Cathepsin K-positive stromal fibroblasts may play a crucial role in SCC progression by promoting extracellular matrix degradation, thereby facilitating SCC growth and invasion into surrounding tissue and vasculature. CTSK inhibitors may be a potential novel therapeutic option to decrease SCC progression.