Computed diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values.

OBJECTIVE: To evaluate the influence of the combinations of b-values on computed diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000 s mm(-2). METHODS: Diffusion-weighted imaging (DWIs) for 31 patients with PCa (65.2 ± 7.1 years) were obtained pre-operatively at different b-values (0, 100, 500, 1000 and 2000 s mm(-2)) on a 3-T MRI. cDWIs at b = 2000 were generated by using six b-value combinations: 0-100 s mm(-2) (cDWI0-100); 0-500 s mm(-2) (cDWI0-500); 100-500 s mm(-2) (cDWI100-500); 0-1000 s mm(-2) (cDWI0-1000); 100-1000 s mm(-2) (cDWI100-1000); and 500-1000 s mm(-2) (cDWI500-1000). These cDWIs and measured DWIs with b = 2000 s mm(-2) (mDWI2000) were evaluated in this setting. To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non-cancerous lesions were evaluated. To compare the detectability of PCa for each DWI, receiver operating characteristic analysis was used. RESULTS: CRs of all cDWIs were significantly higher than those of mDWI2000 (p < 0.05). Areas under the curve of cDWI0-100 (0.62) and cDWI0-500 (0.65) were significantly smaller (p < 0.05) than those of others (cDWI100-500, 0.72; cDWI0-1000, 0.73; cDWI100-1000, 0.71; cDWI500-1000, 0.74; mDWI2000, 0.72). CONCLUSION: The combinations of b-values influenced image quality and diagnostic ability of cDWIs for PCa detection. The combinations of b ≥ 100 and b ≥ 500 s mm(-2), as well as b = 0 and b = 1000 s mm(-2), were optimal in this study. ADVANCES IN KNOWLEDGE: For generating the useful cDWI for PCa detection, radiologists should take care of the combination of b-values when including low b-values.

Evaluation of the operative methods for Graves' disease.

AIM: In Japan, surgery for Graves' disease (GD), which is considered to be a radical therapy, has been restricted by various guidelines. Nevertheless, some patients benefit from surgery. We sought to identify a reasonable operative method for GD by comparing the efficacy and safety among patients undergoing different extents of thyroidectomy. METHODS: A total of 162 patients underwent thyroidectomy for GD between 2003 and 2012 in our department. We compared the clinical factors among those who underwent subtotal thyroidectomy (ST), near-total thyroidectomy (NTT), and total thyroidectomy (TT). RESULTS: The ST, NTT, and TT groups included 111, 21, and 30 patients, respectively. The patient sex, period between disease onset and surgery, and preoperative thyroidal function were not substantially different among the three groups. With regard to surgical variables, the duration of surgery, amount of blood loss, and postoperative length of hospitalization were not substantially different among the three groups. Postoperative recurrent laryngeal nerve (RLN) palsy was transient in all cases, but the rate was significantly higher in the TT group compared to the other two groups (P<0.001). The incidences of transient hypocalcemia and permanent hypoparathyroidism were not substantially different among the groups. The proportion of patients who required the postoperative administration of levothyroxine was significantly lower in the ST group compared to the TT and NTT groups. Hyperthyroidism recurrence was noted in eight patients in the ST group (7.2%). CONCLUSION: NTT for GD is thus considered to be a reasonable operative method regarding both efficacy and safety.

Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

Leiomyosarcoma of the broad ligament: a case report with CT and MRI images.

Primary leiomyosarcoma of the broad ligament is a very rare and highly malignant gynecological tumor. The authors report a 61-year-old postmenopausal woman with signs and symptoms of malignant ovarian tumor. Preoperative magnetic resonance imaging (MRI) was interpreted as being suspicious for malignant tumors, such as an ovarian cancer or a leiomyosarcoma of the broad ligament, so laparotomy was performed. Macroscopically, the tumor was revealed with a 18 x 13.7 x 9.5 cm degenerated, multiple cystic part and solid whitish part arising from broad ligament which on histopathology proved to be leiomyosarcoma. To the best of the authors' knowledge, primary leiomyosarcoma of the broad ligament has been documented in 21 reports or so, and no imaging findings are available. Here the authors present the MRI findings of primary leiomyosarcoma of the broad ligament.

Hormone replacement therapy and breast density changes.

OBJECTIVES: To compare the incidence of increased breast density and tenderness in postmenopausal women associated with transdermal (Estalis/Combipatch), Novartis, Basel, Switzerland) and oral (Kliogest), Schering AG, Berlin, Germany) hormone replacement therapy (HRT). METHODS: A total of 202 postmenopausal women were randomized to transdermal or oral HRT. Mammograms obtained at study entry and after 1 year of treatment were assessed for percent breast density by means of the digital segmentation and thresholding technique. Breast tenderness was assessed at each study visit. RESULTS: The mean breast density by ANCOVA after adjusting for screening value at study end was significantly lower for women using Estalis (38.4%, standard error 0.9%) compared with Kliogest (46.9%, standard error 1.5%) (p<0.0001). Significantly fewer women using transdermal HRT had an increase in mammographic breast density or breast tenderness compared to oral HRT. Of the women using transdermal HRT, 39.1% had no change in breast density compared to 15.7% for women using oral HRT. Only 4% of women using transdermal HRT had a marked increase in density (>25%) compared to 15.7% of women using oral HRT. Overall, 36.0% of patients in the transdermal group reported breast tenderness at some point during the 1-year study, compared with 57.6% in the oral HRT group (p=0.0002). CONCLUSION: Transdermal HRT use is associated with a significantly lower incidence of increased mammographic breast density and breast tenderness compared with oral HRT.

Gastric T-cell lymphoma presenting with epithelioid granulomas mimicking tuberculosis in regional lymph nodes.

In patients with malignant lymphomas, a sarcoid reaction is occasionally observed. However, lymphoma-related granulomas with caseous necrosis are rare. We describe such a case of T-cell gastric lymphoma that was difficult to diagnose. A 50-year-old man was referred to our hospital because of abnormal gastric endoscopic findings: hypertrophic folds with narrowing of the gastric lumen and multiple ulcers in the body. Gastric biopsy specimens showed non-specific inflammation. An open biopsy of the enlarged gastric regional lymph nodes was performed. The sections revealed effacement of the normal architecture and replacement by numerous epithelioid granulomas accompanied by Langhan's type giant cells with or without central caseous necrosis, strongly suggesting tuberculosis. However, mycobacteria and other causative organisms were not detected, and an anti-tuberculous regimen was ineffective. Repeat gastric biopsies were performed and, finally, atypical lymphocytes were observed infiltrating the mucosa. The patient was diagnosed with gastric T-cell lymphoma based on the results of immunohistochemical stainings. After chemotherapy, a total gastrectomy was performed. The diagnosis of gastric T-cell lymphoma with a sarcoid reaction was confirmed by histological findings of the sections. Namely, the gastric wall was replaced by atypical lymphocytes showing the phenotype of helper T cells, admixed with epithelioid granulomas with Langhan's type giant cells. Thus, this case suggests that regional lymph nodes in gastric lymphomas may be present as epithelioid granulomas with caseous necrosis, mimicking tuberculosis.

Relationship of leptin level with metabolic disorders and hypertension in Japanese type 2 diabetes mellitus patients.

Leptin is considered to play an important role in the regulation of body weight and metabolism in obese individuals. However, the relationship of leptin with metabolic disorders or vascular complications in type 2 diabetic patients has yet to be elucidated. In this study, we investigated the association of leptin levels with clinical parameters (glycemic control, lipid levels, abdominal fat distribution) and investigated the leptin levels of diabetic patients with and without vascular complications in Japanese diabetic patients. In male and female patients, leptin levels were significantly associated with body mass index (BMI), percent body fat, insulin level, triglyceride (TG) level, total abdominal fat area (TFA), visceral fat area (VFS), and subcutaneous fat area (SFA). Only in male patients, leptin levels were inversely correlated with HDL-cholesterol, fasting plasma glucose (FPG), and HbA(1C). Leptin levels in male and female patients with hypertension were higher than in those without hypertension. Leptin levels of both males and females with angiopathy were not statistically different from those without angiopathy. In conclusion, leptin is involved in various metabolic disorders and hypertension, and we speculate that it may not be strongly associated with vascular complications in Japanese diabetic individuals.

Comparison of risk factors of macrovascular complications. Peripheral vascular disease, cerebral vascular disease, and coronary heart disease in Japanese type 2 diabetes mellitus patients.

Although macroangiopathies such as peripheral vascular disease (PVD), cerebral vascular disease (CVD), and coronary heart disease (CHD) can often be observed in patients with diabetes mellitus, they are not specific for diabetes mellitus. Moreover, it is unclear whether their progressive mechanism is different. In the present study, we compared the risk factors among the diabetic macrovascular complications. Univariate analyses showed that in all patients, age at examination, duration of diabetes, thrombin-antithrombin III complex (TAT) level, fibrinogen level, lipoprotein (a) (Lp(a)) level, total cholesterol (T-Chol) level, and existence of microagiopathy were risk factors for PVD. Age, duration of diabetes, insulin level, TAT level, fibrinogen level, HDL cholesterol (HDL-Chol) level, hypertension, and nephropathy were risk factors for CVD. Only fibrinogen level was a risk factor for CHD. Moreover, Lp(a) level was a risk factor for PVD and CVD in male patients, but not in females. On the other hand, insulin level was a risk factor for CVD in female patients, but not in males. Multivariate analyses showed that TAT level, T-Chol level, and neuropathy were independent variables for PVD and that age, TAT level, and HDL-Chol level were independent variables for CVD. On the other hand, only fibrinogen level was the independent variable for CHD in males. Our results suggest that the progressive mechanism of PVD and CVD might be different from that of CHD and might differ according to gender in Japanese diabetic patients.

Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy.

Diabetes is associated with a hypercoagulable state. Blood hypercoagulability may accelerate atherosclerosis and the diabetic microvascular complications. Thrombin-antithrombin III complex (TAT) and fibrinogen levels are parameters of coagulation and fibrinolysis. In the present study, we examined the risk factors for the diabetic microangiopathy including TAT and fibrinogen levels. To investigate the relationship between the clinical parameters and microangiopathy in type 2 diabetic patients, the clinical parameters of subjects with microangiopathy were compared with those of subjects without microangiopathy. The clinical parameters were as follows: age at examination, duration of diabetes, fasting plasma glucose (FPG) level, HbA(1C) level, insulin level, TAT level, fibrinogen level, lipoprotein (a) (Lp(a)) level, total cholesterol level, triglyceride level, HDL cholesterol level and existence of hypertension. The plasma TAT and fibrinogen levels were significantly higher in patients with retinopathy or nephropathy than in patients without these complications. Moreover, fibrinogen levels of patients with microalbuminuria or background retinopathy were significantly higher than those of patients with normoalbuminuria or no retinopathy. The duration of diabetes was significantly longer in patients with any microangiopathy than in patients without it. Multiple regression analyses showed that duration and fibrinogen level were independent factors associated with the existence of retinopathy or nephropathy. Our data show that the disorder of coagulation and fibrinolysis is significantly associated with diabetic retinopathy and nephropathy and exists at the early stage of microangiopathy.

Allergy to ethylenediamine and steroid.

Intravenous preparations combining aminophylline and a steroid are used frequently in the treatment of bronchial asthma attacks. However, anaphylactoid reactions to such preparations have been rarely observed. We report the case of a 31-year-old man with aminophylline and steroid allergy. Aminophylline is the ethylenediamine salt of theophylline. In our patient, aminophylline, ethylenediamine and various steroids were found to be positive in the intradermal test. The challenge test with intravenous aminophylline was positive, while that with oral theophylline was negative. Ethylenediamine is used in everyday products such as shellacs and rubber products. In the case of our patient, his asthma worsened following the remodelling of his restaurant. Occupational asthma due to exposure to ethylenediamine is also discussed.

Limb-sparing surgery with reinnervated free-muscle transfer following radical excision of soft-tissue sarcoma in the extremity.

Limb-sparing surgery is the preferred approach in the management of patients with high-grade soft-tissue sarcomas when local disease can be completely resected. However, conventional treatment focuses only on restoration of basic functions to the remnant limb. Lost functions are not restored to normal, leaving the patient with variable degrees of functional disabilities. This in turn may necessitate further massive reconstructive procedures. Transferred reinnervated free muscles were used to reconstruct functions lost after radical resection of malignant soft-tissue sarcoma of the extremities in 17 patients. The long-term functional outcome included survival of transplanted muscle, speed of neural recovery, and muscle strength and disabilities. All muscles survived. Postoperative follow-up ranged from 27 to 106 months. All muscles except those in a 75-year-old patient were successfully reinnervated. Powerful strength and almost normal limb functions were obtained. Functional scoring of the patients according to the rating system of the Musculoskeletal Tumor Society was 87 percent for the lower extremity and 93 percent for the upper extremity. All patients are presently disease-free. Use of the reinnervated free-muscle transfer in limb-sparing surgery after resection of soft-tissue sarcoma in the extremity may be indicated in the young adult when radical excision of the tumor will result in severe motor functional loss, provided adequate clearance can be obtained and that there is no presence of distant metastasis.

Increased thresholds for long-term potentiation and contextual learning in mice lacking the NMDA-type glutamate receptor epsilon1 subunit.

The NMDA-type glutamate receptor (GluR) channel, composed of the GluRepsilon and GluRzeta subunits, plays a key role in synaptic plasticity in the CNS. The mutant mice lacking the GluRepsilon1 subunit exhibited a reduction in hippocampal long-term potentiation (LTP), but a stronger tetanic stimulation restored the impairment and the saturation level of LTP was unaltered. These results suggest an increase of threshold for LTP induction in the GluRepsilon1 mutant mice. After a series of backcrosses we established a GluRepsilon1 mutant mouse line with a 99.99% pure C57BL/6 genetic background. The performance of the mutant mice in tone- and context-dependent fear conditioning tests was comparable with that of the wild-type mice. However, a significant difference in the extent of contextual learning became apparent when the chamber exposure time before footshock was shortened. Furthermore, there was a significant difference in freezing responses immediately after footshock on the conditioning day between the wild-type and mutant mice, and the difference was not restored by longer chamber exposure in contrast to the contextual learning on the next day of the conditioning. These results suggest that the GluRepsilon1 subunit of the NMDA receptor channel is a determinant of thresholds for both hippocampal LTP and contextual learning and plays differential roles in two forms of contextual fear memories.

Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.

Extended wrap-around flap for thumb reconstruction following radical excision of a congenital arteriovenous fistula.

A 38-year-old woman presented with a large congenital arteriovenous fistula in her left hand with ischaemic atrophy of the thumb and index finger. Radical resection of the lesion and ray amputation of the index finger was done. To allow radical excision and reconstruction of the thumb and skin defect, we used an extended wrap-around flap. This flap is useful for primary reconstruction of the thumb following radical excision of a congenital arteriovenous fistula involving the thumb.

Free muscle transfer can restore hand function after injuries of the lower brachial plexus.

One pattern of injury to the brachial plexus shows recovery of the fifth and sixth cervical nerves but little else. These patients have useful shoulders and functional elbow flexion, but elbow and wrist extension is weak or absent. Their hand function is negligible. We restored hand function in three such patients using free functioning muscle transfer for finger flexion and transfer of the sensory rami of the intercostal nerve to the ulnar nerve for sensation. Supplementary operations to restore elbow and wrist extension were necessary in one patient.

Endoscopic harvesting of the gracilis muscle for reinnervated free-muscle transfer.

Reinnervated functioning free-muscle transfer has proven to be invaluable in numerous reconstructive procedures. However, one problem that remains unsolved after transferring the muscle is the presence of a long and cosmetically unacceptable scar at the donor site. This scar has undermined patients' satisfaction with the procedure despite its excellent functional results. In an attempt to resolve this problem, the authors harvested the gracilis muscle endoscopically and now report their technique and results. To create an optical cavity in harvesting the gracilis muscle endoscopically, they devised a lifting apparatus, which is described. Comparative study showed that endoscopic harvesting of the gracilis produced a significantly shorter scar, but took 1.5 times longer than conventional method.

Significance of elbow extension in reconstruction of prehension with reinnervated free-muscle transfer following complete brachial plexus avulsion.

Thirty-one patients with complete avulsion of the brachial plexus underwent reconstruction of elbow extension by intercostal nerve transfer following reconstruction of prehension with either a single or double free-muscle transfer. Long-term results of elbow extension were evaluated in 24 patients. Reinnervation of the triceps muscle took longer than that of the transferred muscle on serial electromyographic examinations, and the eventual strength of the triceps muscle was weak. None attained M5 grade, 2 achieved M4 grade, 4 achieved M3 grade, 8 achieved M2 grade, 5 achieved M1 grade, and another 5 achieved M0 grade. However, despite the weak recovery, 14 patients were able to obtain useful functional recovery of the triceps muscle, enabling it to stabilize the elbow joint against the transferred muscle, which acted as simultaneous elbow flexor and wrist or finger extensor. Elbow stability is imperative in order to obtain voluntary finger function following free-muscle transfer. Should the triceps muscle fail to recover following intercostal nerves neurotization, transferring the reinnervated infraspinatus to the triceps is an optional procedure to provide stabilization of the elbow.