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.

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.

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.

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.

Circadian change of VIP mRNA in the rat suprachiasmatic nucleus following p-chlorophenylalanine (PCPA) treatment in constant darkness.

Neuronal activity of the suprachiasmatic nucleus (SCN) is known to be regulated by two major extrinsic factors conveyed by three anatomically distinct pathways to the SCN: photic stimulus by the direct retinohypothalamic tract (RHT) and the indirect geniculohypothalamic tract (GHT), and information from the brainstem by ascending forebrain serotonergic (5-hydroxytryptamine: 5-HT) tract. It has been shown that VIP mRNA level in neurons of the SCN is altered by external light, but remains stable in constant darkness. In the present study, by using the in situ hybridization technique combined with computer-assisted image analysis, we examined VIP mRNA expression in the SCN of rats in which the two major factors were eliminated, i.e. photic stimulus by exposing animals in total darkness and 5-HT transmission by three-day successive administration of p-chlorophenyl-alanine methylester (an inhibitor of tryptophan hydroxylase, 200 mg/kg, daily). In saline-treated controls, VIP mRNA levels remained almost constant throughout the day. In contrast, in PCPA-treated rats, a significant rhythm of VIP mRNA was observed with a peak at CT 4 and a trough at CT 20. These observations suggest that the removal of photic and 5-HT influence induces VIP mRNA rhythm in the SCN, indicating that VIP mRNA is controlled not only by photic information but also by the circadian clock.

Morphological survey of neurotensin-like immunoreactive neurons in the hypothalamus.

Neurotensin-like immunoreactive neuronal perikarya, fibers and terminals in in the rat hypothalamus were investigated by light and electron microscopic immunocytochemistry. Distributional density and pattern of these elements were clarified. Fine structure of immunoreactive neuronal perikarya with respect to development of cell organellae and immunoreactive dense granules was also elucidated. Features of immunoreactive processes, dendrites and preterminal axons were examined electron microscopically. In addition to the above findings by light and electron microscopic immunocytochemistry, we examined the coexistence of dopamine and neurotensin-like immunoreactive substances in these same neurons in the arcuate and periventricular nuclei. This was proved by the application of fluorescence histochemistry and immunocytochemistry on the same sections. Moreover, we speculated that the ascending noradrenergic neurons influence the neurotensin immunoreactive neurons in the paraventricular nucleus since a marked decrease in the number of neurotensin-like immunoreactive neuronal perikarya was observed after transection of ascending noradrenergic pathway.

Fine structure of NPY-containing neurons in the lateral geniculate nucleus and their terminals in the suprachiasmatic nucleus of the rat.

Fine structures of neuropeptide Y (NPY)-like immunoreactive neuronal perikarya in the lateral geniculate nucleus and their terminals in the suprachiasmatic nucleus were investigated by peroxidase-antiperoxidase immunocytochemistry using male Wistar rats. NPY-like immunoreactive preterminal axons form both axo-somatic and axo-dendritic synapses on the neurons mainly located in the ventral portion of the suprachiasmatic nucleus. Almost all of them appeared as symmetrical synapses. Immunoreactive neuronal perikarya in the lateral geniculate nucleus show good development of cell organelles such as rough-surfaced endoplasmic reticulum and mitochondria. NPY-like immunoreactivity was distributed throughout the perikarya. The functional role of NPY-like immunoreactive terminals in the suprachiasmatic nucleus were briefly discussed.

Light and electron microscopic immunocytochemistry of GRF-like immunoreactive neurons and terminals in the rat hypothalamic arcuate nucleus and median eminence.

Growth hormone-releasing factor (GRF) synthesizing neuronal perikarya and terminals were investigated by light and electron microscopic immunocytochemistry using rat hypothalamus. Immunoreactive neuronal perikarya were located mainly in the ventrolateral part of the arcuate nucleus. They contained well developed cell organella such as mitochondria and rough surfaced endoplasmic reticulum with some expansion. They also contained immunoreactive dense granules (80-120 nm in diameter). On the surface of the immunoreactive neuronal perikarya were frequently found non-immunoreactive axo-somatic synapses. Therefore, the GRF-like immunoreactive neurons were assumed to receive neuronal inputs from other neurons on their neuronal soma. In the external layer of the median eminence large numbers of immunoreactive terminals were distributed particularly around the capillaries of the portal vessel. Electron microscopic immunocytochemistry revealed large numbers of immunoreactive terminals containing immunoreactive dense granules, synaptic vesicles and mitochondria in the vicinity of the basement membrane of the pericapillary space of the portal vessel. Therefore, we concluded that GRF-like immunoreactive substances are released into the portal capillaries from the nerve terminals, which originate from the neuronal perikarya in the ventrolateral part of the arcuate nucleus, and act on growth hormone release in the anterior pituitary. We also suggest that GRF-like immunoreactive neurons have abundant terminal arborization in the external layer of the median eminence.

Light and electron microscopic immunocytochemistry of beta-endorphin/beta-LPH-like immunoreactive neurons in the arcuate nucleus and surrounding areas of the rat hypothalamus.

beta-Endorphin/beta-LPH-like immunoreactive neurons in the hypothalamic arcuate nucleus and its surrounding areas were visualized by light and electron microscopic immunocytochemistry. Immunoreactive processes were found in the vicinity of the pia mater, in the lateral part of the external layer of the median eminence and near the lateral wall of the third ventricle. Neuronal perikarya contained immunoreactive dense granules as well as developed cell organellae. They received neuronal inputs from other neurons through axoplasmic and axodendritic synapses. Immunoreactive neuronal processes containing dense granules and mitochondria were found as preterminal elements on non-immunoreactive neuronal soma and dendrites. Immunoreactive processes also make intimate contact with capillaries in the arcuate nucleus near the median eminence.

Light and electron microscopic immunocytochemistry of neurotensin-like immunoreactive neurons in the rat hypothalamus.

Neurotensin-like immunoreactive neuronal perikarya, fibers and terminals in the rat hypothalamus, particularly in the arcuate nucleus, the paraventricular nucleus and the median eminence, were investigated by light and electron microscopic immunocytochemistry. The main distributional areas of immunoreactive neuronal perikarya were found to be the arcuate nucleus, the periventricular nucleus and the paraventricular nucleus by light microscopic immunocytochemistry. Immunoreactive neuronal perikarya showed a characteristic distributional pattern in the arcuate nucleus. In the paraventricular nucleus they were distributed in both the magnocellular and parvocellular portions. A large number of immunoreactive terminals were observed throughout the external layer of the median eminence, particularly its lateral portion. A moderate number of immunoreactive terminals were also observed in the internal layer of the median eminence. By electron microscopic immunocytochemistry immunoreactive neuronal perikarya both in the arcuate and paraventricular nuclei showed generally well-developed cell organelles such as mitochondria, r-ER, and Golgi complex. In addition, immunoreactive dense granules were dispersed throughout the perikarya. A large number of immunoreactive terminals containing immunoreactive dense granules, clear vesicles and mitochondria were observed in the vicinity of pericapillary spaces of the external layer of the median eminence. This observation strongly suggests that neurotensin-like immunoreactive substance is released into the portal capillaries.

Sexual differences in the distribution of substance P immunoreactive fibers in the ventral horn of the rat lumbar spinal cord.

The distribution of substance P (SP) in the rat spinal cord was investigated by peroxidase-anti-peroxidase immunocytochemistry combined with retrograde horseradish peroxidase (HRP) labeling via the cremaster muscle. In the male rats, a dense network of SP immunoreactive (SP-IR) fibers and terminals was detected in the ventral column of the L1 and L2 segments (Vent L1-2) with a different density and extent from the other segmental levels. These fibers and terminals were accumulated within and around the nucleus centromedialis lumbaris (CM) of the L1 and L2 segments. However, in the female rats, SP-IR fibers and terminals were sparse in the Vent L1-2 without particular segmental differences. HRP-positive motoneurons were located in the CM and surrounded by SP-IR fibers and terminals. These results indicate that the Vent L1-2 of the rat spinal cord shows sexual dimorphism with respect to the regional distribution of SP-IR fibers and terminals, and that motoneurons that innervate the cremaster muscle are innervated by dense SP-IR fibers and terminals.

Changes in vasoactive intestinal peptide mRNA levels in the rat suprachiasmatic nucleus following p-chlorophenylalanine (PCPA) treatment under light/dark conditions.

Photic stimulus and serotonin (5-hydroxytryptamine; 5-HT) are two factors known to regulate vasoactive intestinal peptide (VIP) synthesis in the suprachiasmatic nucleus (SCN). To explore the role of 5-HT in the photic stimulus-induced change in VIP synthesis, we investigated the changes in level of VIP mRNA under a 12 h light/12 h dark cycle following depletion of 5-HT by intraperitoneal administration of p-chlorophenylalanine (PCPA) methyl ester (200 mg/kg concentration) for 3 successive days. To estimate VIP mRNA expression, we performed in situ hybridization using imaging plates combined with microcomputer-based imaging analysis. In light-phase, total signals of VIP mRNA from the PCPA-treated rats showed a significant decrease compared with those from the saline-treated control rats. However, in dark-phase, there were no significant decreases between the PCPA-treated rats and the saline-control rats. The present results strongly suggest that 5-HT neuronal inputs to the SCN interfere with the effect of photic stimulus on VIP synthesis at the mRNA level.

The influence of serotonergic inputs on peptide neurons in the rat suprachiasmatic nucleus: an immunocytochemical study.

The influence of serotonin (5-hydroxytryptamine; 5-HT) innervation on peptide-containing neurons in the rat suprachiasmatic nucleus (SCN) was investigated by peroxidase-anti-peroxidase (PAP) immunocytochemistry. The 5-HT neuronal system was chemically severed by 5,6-dihydroxytryptamine (5,6-DHT) injection into the medial forebrain bundle bilaterally. After this treatment, a marked decrease of vasoactive intestinal peptide (VIP)-like immunoreactivity in neuronal perikarya occurred in the SCN corresponding to a decrease in number of 5-HT immunoreactive fibers and terminals. However, no alteration of arginine-vasopressin-like immunoreactivity was detected between 5,6-DHT-treated animals and the controls. It is speculated that VIP-like immunoreactive neurons play an important role in the SCN under the influence of strong 5-HT innervation.

Serotonin depletion by p-chlorophenylalanine decreases VIP mRNA in the suprachiasmatic nucleus.

The influence of serotonergic inputs on the levels of vasoactive intestinal peptide (VIP) mRNA in the rat suprachiasmatic nucleus (SCN) was examined by in situ hybridization combined with morphometrical analysis. Depletion of serotonin by p-chlorophenylalanine methyl ester (300 mg/kg i.p. daily for 3 days) caused a marked decrease in VIP mRNA signal levels in the ventrolateral part of the SCN. This finding suggests that serotonergic input controls VIP production at the mRNA level.

Vasoactive intestinal peptide (VIP)-like immunoreactive neurons located in the rat suprachiasmatic nucleus receive a direct retinal projection.

The existence of a direct projection from retinal ganglion cells to vasoactive intestinal peptide (VIP)-like immunoreactive neuronal elements in the rat suprachiasmatic nucleus (SCN) was revealed by combining analysis of degenerating axons following enucleation and electron microscopic immunocytochemistry. Degenerating axons appeared to make synaptic contact with VIP-like immunoreactive dendrite and neuronal perikarya in the ventral part of the SCN. The possibility of neuronal input from retinal ganglion cells to axons of VIP-like immunoreactive neurons was also suspected since axo-axonic synapses were detected between degenerating axons and axons with VIP-like immunoreactivity. Thus, VIP-like immunoreactive neurons in the SCN receive several neuronal inputs, including those from the retina, and may play a significant role in circadian entrainment.

Loss of day-night differences in VIP mRNA levels in the suprachiasmatic nucleus of aged rats.

Age-related decreases in circadian oscillating activity are speculated to be one of the causes of psychiatric symptoms. To explore the effects of aging on vasoactive intestinal peptide (VIP) synthesis in the suprachiasmatic nucleus (SCN), we investigated the changes in VIP mRNA levels in aged rats compared with young-adult rats under a light/dark cycle using in situ hybridization combined with microcomputer-based imaging analysis. In the young-adult rats, total signals of VIP mRNA in the light-phase showed a significant decrease compared with those on the dark-phase. The VIP signal level in the aged rats was markedly lower than that in young-adults in both light and dark phases. Moreover, in the aged rats, there were no significant differences in VIP mRNA level between the light and dark phases. These results suggest that gene expression of VIP neurons, a main component of the circadian oscillating system, becomes disturbed in the aged rat brain.

Influence of ascending noradrenergic fibers on the neurotensin-like immunoreactive perikarya and evidence of direct projection of ascending neurotensin-like immunoreactive fibers in the rat central nucleus of the amygdala.

The influence of ascending noradrenergic neuronal input on the neurotensin (NT)-like immunoreactive neuronal perikarya located in the dorsal part of the central nucleus of the amygdala (CNA) was examined using fluorescence histochemistry and peroxidase-antiperoxidase (PAP) immunocytochemistry. Unilateral hemitransection of the ascending noradrenergic pathway by injection of 6-hydroxydopamine into the caudal mesencephalon just rostral to the locus coeruleus caused a marked depletion of immunoreactivity in NT-like immunoreactive neuronal perikarya in the CNA. Ascending noradrenergic neuronal input, therefore, is considered to facilitate production of NT-like immunoreactive substances in neuronal perikarya and to influence on the functional role of the amygdaloid complex. In addition, we obtained evidence of unilateral direct ascending projections of NT-like immunoreactive neurons into the CNA since the disappearance of NT-like immunoreactive processes occurred mainly in the ventral part of the CNA after surgical hemitransection of the ascending neuronal pathway that interrupts the ascending NT-like immunoreactive pathway arising from the neurons in the brain stem.

Influence of ascending noradrenergic fibers on the neurotensin-like immunoreactive neurons in the rat paraventricular nucleus.

Regulation of the neurotensin (NT)-producing neurons by ascending catecholamine fibers in the paraventricular nucleus of the rat hypothalamus was examined using fluorescence histochemistry and immunohistochemistry after the destruction of the ascending catecholamine pathway by 6-hydroxydopamine. On the ipsilaterally operated side, the fluorescence of the catecholamine terminals decreased remarkably in the paraventricular nucleus whereas an accumulation of catecholamine fluorescence was observed in the caudal mesencephalon rostral to the locus coeruleus. In addition, the number of neural perikarya with NT-like immunoreactivity was greatly decreased in the paraventricular nucleus on the operated side compared with the intact side as determined by peroxidase-antiperoxidase immunohistochemistry. This decrease in the NT-like immunoreactive neural perikarya may be due to the disappearance of noradrenergic input to the NT-like immunoreactive neurons through axo-somatic or axo-dendritic synapses.

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.