Reliability and validity of splenic volume measurement by 3‐D ultrasound

Aim: We prospectively evaluated the reliability and validity of splenic volume with 3‐D ultrasound measurement and clarified its clinical usefulness. Methods: Thirty healthy volunteers and 30 patients with cirrhosis were included in this study. All 3‐D ultrasound examinations of splenic volumes were performed twice by two experienced sonographers with transabdominal ultrasound using virtual organ computer‐aided analysis (VOCAL). Reliability was confirmed among all subjects by evaluating within‐observer repeatability and between‐observer reproducibility using intraclass correlation coefficients (ICC) and Bland–Altman plots. Overall between‐instrument agreement of the measurements and computed tomography (CT) volumetry among cirrhotic patients were performed to determine validity. Results: For all 240 examinations, 3‐D ultrasound visualization and measurement of the spleen volume was possible. Mean spleen volume was 104.0 mL for the volunteers and 283.5 mL for the cirrhotic patients. The repeatability was high, with ICC (95% confidence interval) of 0.996 (0.993–0.997) for observer A and 0.997 (0.994–0.998) for observer B. Moreover, the interobserver ICC was 0.996, indicating high reproducibility. Despite the difference in volume between the volunteers and cirrhotic patients, sensitivity analyses indicated consistent results for both groups. Regarding the validity of the 3‐D ultrasound measurement, it also showed moderate to high agreement with CT volumetry, with mean ICC of 0.922 and 0.924 for observers A and B, respectively. The reliability and validity results from the Bland–Altman plots were similar to those from the ICC, with limits of agreement consistently narrow from a clinically practical view. Conclusion: 3‐D ultrasound measurements using VOCAL are valid and reliable in spleen volume examinations.     

Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet

To clarify the molecular mechanism of adipocyte differentiation, we previously isolated a novel gene, factor for adipocyte differentiation (fad) 158, whose expression was induced during the earliest stages of adipogenesis, and its product was localized to the endoplasmic reticulum. We found that the knockdown of fad158 expression prevented the differentiation of 3T3-L1 cells into adipocytes. In addition, over-expression of fad158 promoted the differentiation of NIH-3T3 cells, which do not usually differentiate into adipocytes. Although these findings strongly suggest that fad158 has a crucial role in regulating adipocyte differentiation, the physiological role of the gene is still unclear. In this study, we generated mice in which fad158 expression was deleted. The fad158-deficient mice did not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but had significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Furthermore, although the disruption of fad158 did not influence insulin sensitivity on the chow diet, it improved insulin resistance induced by the high-fat diet. These results indicate that fad158 is a key factor in the development of obesity and insulin resistance caused by a high-fat diet.     

An infant case of macroprolactinemia with transient idiopathic central precocious puberty

Macroprolactinemia was recognized more than a decade ago as a cause of hyperprolactinemia and the prevalence of macroprolactinemia is thought to be 10%-26% of patients with hyperprolactinemia. However, there are few published reports about macroprolactinemia in childhood. We report a 7-year-and-1-month-old girl with hyperprolactinemia due to macroprolactinemia with the complication of transient idiopathic central precocious puberty (ICPP). At the age of 6 years and 9 months, she was diagnosed with ICPP at another clinic, on the basis of isolated mammary development and increased height velocity with slightly advanced bone age. At that time, the unexpected finding of high PRL level was also observed. Four months later, she was referred to our clinic for persistently high PRL level. At this time, other endocrinological data showed prepubertal stage and we demonstrated macroprolactinemia and the presence of anti-PRL autoantibody. After other causes of hyperprolactinemia such as prolactinoma and stress were ruled out, we finally diagnosed her with hyperprolactinemia due to macroprolactinemia. Because most patients with macroprolactinemia are symptom-free despite hyperprolactinemia and drug therapy would not be indicated, macroprolactinemia should be suspected even in children to avoid unnecessary examinations and treatments.     

Two cases of primary female urethral cancer

Herein, we report two cases of female urethral cancer. Case 1 presented with acute urinary retention and case 2 presented with a painful perineal mass. Magnetic resonance imaging (MRI) revealed a urethral tumor in both cases. Histopathological examination of transperineal biopsy specimens from both patients suggested clear cell adenocarcinoma in case 1 and squamous cell carcinoma in case 2. Both cases underwent total urethrectomy with partial resection of the vaginal wall and cystostomy urinary diversion. With reference to case 1, obturator lymph node metastases were observed during surgery, and treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin following surgery. However, metastases appeared in the lung 6 months after initial treatment and she died 20 months after surgery. For case 2, tumor marker failure was observed 5 months after surgery. The same combined treatment was performed and a complete response was obtained. At 19 months after surgery, the patient showed no evidence of recurrence.     

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.     

Relationship between soluble MICA and the MICA A5.1 homozygous genotype in patients with oral squamous cell carcinoma

NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Polymorphisms in MICA may influence its binding to the NKG2D. The soluble form of MICA is released from the surface of tumor cells of epithelial origin. Whereas MICA expressed on the cell surface stimulates the immunoreceptor natural killer group 2, member D (NKG2D), the secreted form down-regulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between MICA gene microsatellite polymorphisms and serum levels of soluble MICA in patients with oral squamous cell carcinoma (OSCC). We found that patients with OSCC were more likely to have the A5.1 allele when compared to healthy subjects and also more likely to be homozygous for this allele (p = 0.041). Patients with the homozygous A5.1 genotype had higher levels of soluble MICA (p = 0.031) and a lower survival rate (p = 0.026).     

A long-term survival case of recurrent pancreatic vipoma with liver metastases treated by a combination of surgical resection and loco-regional therapies

We report a case of recurrent pancreatic VIPoma with liver and peritoneal metastases who has been surviving over 7 years by a successful treatment with a combination of surgical resection and loco-regional therapies. A 59-year-old female underwent distal pancreatectomy for pancreatic endocrine tumor. Five years after pancreatectomy, she had a recurrence of liver and peritoneal metastases with the symptoms by hypersecretion of VIP, and she underwent hepatectomy and peritoneal tumor resection. Seven months later, multiple liver metastases appeared and were treated with transcatheter arterial chemoembolization (TACE). Additionally radiofrequency ablation( RFA) for remnant viable lesion was performed. Seven years and eight months after primary panceatectomy and two years and six months after resection of the liver and peritoneal recurrences, she is now disease-free with good quality of life. The progression of well-differentiated pancreatic neuroendocrine carcinoma is usually slow. It is potentially useful in controlling of liver metastases to combine the loco-regional therapy like TACE and RFA with surgical resection.     

Re-evaluation of lipiodolized transarterial chemoembolization therapy for intrahepatic recurrence of hepatocellular carcinoma after curative liver resection

Background/Purpose  While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified. Methods  Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed. Results  The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio. Conclusions  Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.