Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte- and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption.     

Single-fulcrum laparoscopic cholecystectomy: a single-incision and multi-port technique

Background: Single-incision laparoscopic cholecystectomy (LC) is still technically demanding and usually requires specially designed instruments. This article describes our own technique, a single-fulcrum LC using only standard ports and instruments. Methods: Between March 2009 and December 2010, 130 consecutive patients, all scheduled to undergo elective LC, underwent this single-fulcrum LC for benign gallbladder disease. Perioperative surgical outcomes were retrospectively evaluated. Results: One hundred and ten patients (84.6%) underwent successful single-fulcrum LC, and 20 patients (15.4%) were converted to conventional surgery (n= 18) or required additional trocars (n= 2) during the procedure because of umbilical hernia (n= 3), severe inflammation or adhesion (n= 9), impacted cystic duct stone (n= 3), anatomical anomaly (n= 3) and iatrogenic injury (n= 2). Two intraoperative complications (iatrogenic injury) were securely managed using additional trocars and there was no post-operative morbidity or mortality. This single-fulcrum LC could be performed with comparable cost to conventional LC, and the sequential operative time showed reasonable learning curve. Conclusion: Single-fulcrum LC is feasible, safe and quite reproducible. The surgical wound can be dramatically reduced at a similar cost to conventional LC. It may be an alternative procedure for most uncomplicated benign gallbladder disease.     

Prediction of Recurrence after Curative Resection of Hepatocellular Carcinoma using Liver Stiffness Measurement (FibroScan?)

Background

The purpose of this study was to investigate whether preoperative liver stiffness measurement (LSM) can predict recurrence after curative resection of hepatocellular carcinoma (HCC). LSM using FibroScan^? can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection of HCC.

Methods

Between February 2006 and March 2009, 133 patients who underwent preoperative LSM and curative resection for HCC were enrolled in this prospective study. LSM values were analyzed for association with recurrence, together with other clinical variables.

Results

The mean age of the patients (117 men and 16 women) was 57?years. During the follow-up period (median, 25.0 (range, 3.0?C54.6) months), HCC recurred in 62 (46.6?%) patients. In multivariate analysis, together with satellite nodule and Edmonson-Steiner grade III?CIV, LSM was selected as an independent predictor of recurrence (P?<?0.05; hazard ratio, 1.034; 95?% confidence interval, 1.007?C1.061). When the study population was stratified into two groups using the optimal cutoff value (13.4?kPa) that maximized the sum of sensitivity (64.7?%) and specificity (76.1?%) from time-dependent receiver operating characteristic curves (area under the receiver operating characteristic curve?=?0.676), patients with LSM values >13.4?kPa were at a significantly greater risk for recurrence with a hazard ratio of 1.925 (P?=?0.01; 95?% confidence interval, 1.17?C3.168) compared with those with LSM values ??13.4?kPa.

Conclusions

Our data suggest that LSM can be a useful predictor of recurrence after curative resection of HCC.     

Surgical treatment of temporal bone chondroblastoma

BACKGROUND: Temporal bone chondroblastoma is a rare primary bone tumor that affects the floor of the middle cranial fossa. This tumor is known to have high recurrence rate after curettage, and wide resection is therefore recommended. However, the literature provides little information regarding long-term results after wide resection of temporal bone chondroblastoma. METHODS: Four cases of surgically treated temporal bone chondroblastoma underwent long-term follow-up. RESULTS: Four patients, 3 males and 1 female, with mean age of 34, were surgically treated at the neurosurgery department of Keio University Hospital. Two patients were treated for recurrent tumor and the other two for new disease. In all cases the tumor mainly involved the mandibular fossa with variable degree of infiltration into tympanic and petrous parts. The tumor was totally removed via zygomatic approach in all patients. In 3 patients, the mandibular condyle was removed to expose the tumor. These patients had temporary malocclusion and restricted motion postoperatively, which resolved within 3 to 12 months with conservative treatment. All patients have no recurrence to date with a mean follow-up period of 9 years. CONCLUSION: Temporal bone chondroblastoma was removed totally with skull base surgical technique and no recurrence has occurred for 6 to 13 years postoperatively. We found that removal of the mandibular head does not cause permanent problems of mastication in patients with normal dentures.     

The anatomical basis for reverse first to fifth dorsal metacarpal arterial flaps

This study discusses the anatomical basis for reverse first to fifth dorsal metacarpal arterial flaps. The arterial pattern and size of the first to fifth dorsal metacarpal arteries were examined in 20 fresh cadaver hands. Their connections to the palmar arterial system at the metacarpal head were observed, and the location, number and diameter of skin perforators from each dorsal metacarpal artery were measured. The first to fourth dorsal metacarpal arteries were found in all specimens; the fifth dorsal metacarpal artery was found in 19 of our 20 specimens. The mean diameters of the first to fifth arteries at their bifurcation site were 0.6, 0.8, 0.5, 0.4 and 0.2 mm, respectively. Each artery gave off four to eight skin perforators (diameter: 0.1-0.3 mm) between the metacarpal head and base. The first to third dorsal metacarpal arteries consistently connected to the palmar arterial system, and connections between the fourth and fifth dorsal metacarpal arteries and the palmar system were found in 65% and 40% of specimens.     

Reduced Field-of-View Diffusion-Weighted Magnetic Resonance Imaging of the Pancreas: Comparison with Conventional Single-Shot Echo-Planar Imaging

ObjectiveTo investigate the image quality (IQ) and apparent diffusion coefficient (ADC) of reduced field-of-view (FOV) di-ffusion-weighted imaging (DWI) of pancreas in comparison with full FOV DWI.ResultsOn qualitative analysis, reduced FOV DWI showed better anatomic structure visualization (2.76 ± 0.79 at b = 0 s/mm² and 2.81 ± 0.64 at b = 400 s/mm²), lesion conspicuity (3.11 ± 0.99 at b = 0 s/mm² and 3.15 ± 0.79 at b = 400 s/mm²), IQ score (8.51 ± 2.05 at b = 0 s/mm² and 8.79 ± 1.60 at b = 400 s/mm²), and higher clinical utility (3.41 ± 0.64), as compared to full FOV DWI (anatomic structure, 2.18 ± 0.59 at b = 0 s/mm² and 2.56 ± 0.47 at b = 500 s/mm²; lesion conspicuity, 2.55 ± 1.07 at b = 0 s/mm² and 2.89 ± 0.86 at b = 500 s/mm²; IQ score, 7.13 ± 1.83 at b = 0 s/mm² and 8.17 ± 1.31 at b = 500 s/mm²; clinical utility, 3.14 ± 0.70) (p < 0.05). Artifacts were significantly improved on reduced FOV DWI (2.65 ± 0.68) at b = 0 s/mm² (full FOV DWI, 2.41 ± 0.63) (p < 0.001). On quantitative analysis, there were no significant differences between the 2 DWI sequences in ADCs of various pancreatic lesions and parenchyma (p > 0.05). ADCs of adenocarcinomas (1.061 × 10^-3 mm²/s ± 0.133 at reduced FOV and 1.079 × 10^-3 mm²/s ± 0.135 at full FOV) and neuroendocrine tumors (0.983 × 10^-3 mm²/s ± 0.152 at reduced FOV and 1.004 × 10^-3 mm²/s ± 0.153 at full FOV) were significantly lower than those of parenchyma (1.191 × 10^-3 mm²/s ± 0.125 at reduced FOV and 1.218 × 10^-3 mm²/s ± 0.103 at full FOV) (p < 0.05).ConclusionReduced FOV DWI of the pancreas provides better overall IQ including better anatomic detail, lesion conspicuity and subjective clinical utility.     

Diagnostic Performance of CT Angiography in Patients Visiting Emergency Department with Overt Gastrointestinal Bleeding

Objective

To investigate the diagnostic performance of computed tomography angiography (CTA) in identifying the cause of bleeding and to determine the clinical features associated with a positive test result of CTA in patients visiting emergency department with overt gastrointestinal (GI) bleeding.

Materials and Methods

We included 111 consecutive patients (61 men and 50 women; mean age: 63.4 years; range: 28-89 years) who visited emergency department with overt GI bleeding. They underwent CTA as a first-line diagnostic modality from July through December 2010. Two radiologists retrospectively reviewed the CTA images and determined the presence of any definite or potential bleeding focus by consensus. An independent assessor determined the cause of bleeding based on other diagnostic studies and/or clinical follow-up. The diagnostic performance of CTA and clinical characteristics associated with positive CTA results were analyzed.

Results

To identify a definite or potential bleeding focus, the diagnostic yield of CTA was 61.3% (68 of 111). The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 84.8% (67 of 79), 96.9% (31 of 32), 98.5% (67 of 68), and 72.1% (31 of 43), respectively. Positive CTA results were associated with the presence of massive bleeding (p = 0.001, odds ratio: 11.506).

Conclusion

Computed tomography angiography as a first-line diagnostic modality in patients presenting with overt GI bleeding showed a fairly high accuracy. It could identify definite or potential bleeding focus with a moderate diagnostic yield and a high PPV. CTA is particularly useful in patients with massive bleeding.     

The unrecognized epidemic of blunt carotid arterial injuries: early diagnosis improves neurologic outcome.

OBJECTIVE: To determine the benefit of screening for blunt carotid arterial injuries (BCI) in patients who are asymptomatic. SUMMARY BACKGROUND DATA: Blunt carotid arterial injuries have the potential for devastating complications. Published studies report 23% to 28% mortality rates, with 48% to 58% of survivors having permanent severe neurologic deficits. Most patients have neurologic deficits when the injury is diagnosed. The authors hypothesized that screening patients who are asymptomatic and instituting early therapy would improve neurologic outcome. METHODS: The Trauma Registry of the author's Level I Trauma Center identified patients with BCI from 1990 through 1997. Beginning in August 1996, the authors implemented a screening for BCI. Arteriography was used for diagnosis. Patients without specific contraindications were anticoagulated. Endovascular stents were deployed in the setting of pseudoaneurysms. RESULTS: Thirty-seven patients with BCI were identified among 15,331 blunt-trauma victims (0.24%). During the screening period, 25 patients were diagnosed with BCI among 2902 admissions (0.86%); 13 (52%) were asymptomatic. Overall, eight patients died, and seven of the survivors had permanent severe neurologic deficits. Excluding those dying of massive brain injury and patients admitted with coma and brain injury, mortality associated with BCI was 15%, with severe neurologic morbidity in 16% of survivors. The patients who were asymptomatic at diagnosis had a better neurologic outcome than those who were symptomatic. Symptomatic patients who were anticoagulated showed a trend toward greater neurologic improvement at the time of discharge than those who were not anticoagulated. CONCLUSIONS: Screening allows the identification of asymptomatic BCI and thereby facilitates early systemic anticoagulation, which is associated with improved neurologic outcome. The role of endovascular stents in the treatment of blunt traumatic pseudoaneurysms remains to be defined.     

Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound

Objectives

The aim of our study was to evaluate the tumour volume doubling time (TVDT) of molecular breast cancer subtypes by serial ultrasound (US).

Methods

Sixty-six patients (mean age, 50 years; range, 29–78 years) with invasive breast cancer underwent initial and follow-up breast US examinations (at least three months apart) with no intervention. TVDT was determined using the tumours’ greatest dimensions in two orthogonal planes. The results were compared with clinical, imaging, and tumour variables and molecular subtypes (oestrogen receptor [ER]-positive, human epidermal growth factor receptor 2 [HER2]-positive, and triple negative) using a multiple linear regression analysis.

Results

TVDT exhibited a wide range (46–825 days; median, 141 days) with an overall mean of 193?±?141 days and mean values of 241?±?166 days for ER-positive tumours (n?=?37), 162?±?60 days for HER2-positive tumours (n?=?12), and 103?±?43 days for triple-negative tumours (n?=?17) (P?P?Conclusions TVDT differed significantly among the three molecular breast cancer subtypes, with the triple-negative tumours showing the fastest growth.

Key Points

? Knowledge of tumour volume doubling time provides clues for improving screening. ? TVDT assessed by serial US differed significantly between breast cancer subtypes. ? Triple-negative tumours had 2.4-fold shorter TVDT compared to ER-positive tumours. ? Tumours classified as BI-RADS 3 had shorter TVDT than BI-RADS 4.