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PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.
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Craniofaringioma , Neuroendoscopia , Neoplasias Hipofisárias , Radiocirurgia , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/radioterapia , Masculino , Feminino , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/radioterapia , Adulto , Pessoa de Meia-Idade , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Neuroendoscopia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem , Adolescente , Criança , Cistos/cirurgia , Idoso , Terapia Combinada/métodosRESUMO
Introduction: In psychotherapy, it is important to establish and deepen a therapeutic trusting relationship, but patients who have experienced extreme adversity in childhood tend to have difficulty in building such a relationship. This paper reports a case of fibromyalgia with adverse childhood experiences (ACEs) in which a nonverbal approach was successful in building a trusting relationship. Case and methods: The patient is a woman in her late 40s. She had strong anger rooted in ACEs, including neglect by her father, a feeling of unfair parenting by her mother compared to her younger brother, overcontrol of her life by her mother, and sexual abuse by her uncle. She was filled with strong interpersonal distrust and anger, and the experience of an unsuccessful surgery compounded her distrust of medical care. The therapist initially had severe difficulty in verbal interaction with the patient. When conducting "drawing" therapy, she ignored the therapist's comments and completely blacked out the drawing paper. However, the patient-therapist relationship gradually changed, and verbal interaction became possible through the use of nonverbal approaches such as framing her drawing paper and "Towel Baby Holding." Results: The therapist was able to understand the patient's emotions through these nonverbal approaches and to communicate with the patient that she understood her feelings. This approach was also successful in the patient's understanding of her own pathology. The patient became able to honestly express her feelings in words, which eventually enabled her to be introduced to mindfulness therapy, leading to a favorable treatment course. Conclusion: For patients with ACEs, a nonverbal approach helps build a therapeutic relationship and plays an important role in understanding the patient.
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OBJECTIVES: Laparoscopic adrenalectomy has been the gold standard surgical procedure. However, the adaptation criteria for malignant tumors and predictors of perioperative outcomes are not well defined. Therefore, this study tried to identify valid predictors for perioperative outcomes of laparoscopic adrenalectomy and consider the adaptation criteria. METHODS: We retrospectively reviewed the preoperative and perioperative data of 216 patients who underwent transperitoneal laparoscopic adrenalectomy in our hospital. Preoperative factors associated with perioperative outcomes were analyzed using multiple regression analysis. RESULTS: Among 216 patients, 165 (76.4%), 26 (12.0%), and 25 (11.6%) were suspected of having benign tumors, pheochromocytoma, and malignant tumors, respectively. Median tumor size was 25.0 mm (interquartile range 18.0-35.0); median perirenal fat thickness was 9.2 mm (interquartile range 4.9-15.6) on preoperative computed tomography scans. The median operative time was 145.5 min (interquartile range 117.5-184.0) and the median estimated blood loss was 0.0 mL (interquartile range 0.0-27.3). Perirenal fat thickness (p < 0.001), tumor size (p < 0.001), and malignant tumors (p = 0.020) were associated with operative time, and perirenal fat thickness (p = 0.038) and malignant tumors (p = 0.002) were associated with estimated blood loss. CONCLUSIONS: Perirenal fat thickness, tumor size, and malignant tumors are valid predictors of the surgical outcomes of transperitoneal laparoscopic adrenalectomy. As only perirenal fat thickness is associated with both surgical outcomes except for malignant tumors, it is a powerful predictor. Transperitoneal laparoscopic adrenalectomy for large malignant adrenal tumors with thick perirenal fat should be performed with caution.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Laparoscopia/métodos , Adrenalectomia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Resultado do TratamentoRESUMO
Pasireotide, which has a high affinity for somatostatin receptor (SSTR) 5, has attracted attention as a new treatment for refractory Cushing's disease. The patient was a 28-year-old man. He had refractory Cushing's disease and underwent multiple surgeries, radiotherapy, and medication therapy. An examination of the adenoma by immunohistochemistry revealed a low SSTR5 expression. An USP8 mutation was not detected by reverse transcription polymerase chain reaction. Although we administered pasireotide, it was ineffective. While a further investigation is necessary, the analysis of SSTR5 expression may support the prediction of the efficiency of pasireotide for Cushing's disease. We report this case as a useful reference when considering whether or not to use pasireotide for refractory corticotroph adenomas.
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Hipersecreção Hipofisária de ACTH , Receptores de Somatostatina , Adulto , Humanos , Masculino , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/genética , Receptores de Somatostatina/genética , Somatostatina/análogos & derivados , Somatostatina/uso terapêuticoRESUMO
Male patients with acromegaly frequently have hypogonadism. However, whether excess GH affects gonadal function remains unclear. We retrospectively compared clinical features affecting total testosterone (TT) and free testosterone (FT) levels between 112 male patients with acromegaly and 100 male patients with non-functioning pituitary adenoma (NFPA) without hyperprolactinemia. Median maximum tumor diameter (14.4 vs. 26.5 mm) and suprasellar extension rate (33 vs. 100%) were lower in acromegaly, but LH, FSH, TT, and FT were not significantly different. In acromegaly, TT was less than 300 ng/dL in 57%, and FT was below the age-specific reference range in 77%. TT and FT were negatively correlated with GH, IGF-1, and the tumor size, and positively correlated with LH. In NFPA, they were positively correlated with IGF-1, LH, FSH, ACTH, cortisol, and free T4, reflecting hypopituitarism. Multiple regression analysis showed that TT and FT had the strongest correlation with GH in acromegaly, and with LH in NFPA. Surgical remission was achieved in 87.5% of 56 follow-up patients with acromegaly. TT and FT increased in 80.4 and 87.5%, respectively, with a significant increase in LH. In acromegaly, the degree of postoperative increase in TT(FT) correlated with the fold increase of TT(FT)/LH ratio, a potential parameter of LH responsiveness, but not with fold increase of LH, whereas in NFPA it correlated with both. These results suggest that excessive GH is the most relevant factor for hypogonadism in male acromegaly, and may cause impaired LH responsiveness as well as the suppression of LH secretion.
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Acromegalia/complicações , Adenoma/complicações , Hormônio do Crescimento Humano/sangue , Hipogonadismo/etiologia , Neoplasias Hipofisárias/complicações , Testosterona/sangue , Acromegalia/sangue , Adenoma/sangue , Adulto , Humanos , Hipogonadismo/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Estudos Retrospectivos , Adulto JovemRESUMO
SUMMARY: A 50-year-old woman with thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma) was diagnosed due to symptoms of thyrotoxicosis. Preoperatively, she showed thyrotoxicosis with the syndrome of inappropriate secretion of TSH (SITSH) and had a 5 cm nodule in her thyroid gland. Octreotide was administered preoperatively, which helped lower her serum TSH level but not her thyroid hormone level. These findings were atypical for a patient with TSHoma. The TSHoma was completely resected, and the TSH level dropped below the sensitivity limit shortly after surgery. Interestingly, however, thyroid hormone levels remained high. A clear clue to the aetiology was provided by consecutive thyroid scintigraphy. Although preoperative thyroid scintigraphy did not show a hot nodule and the mass was thought to be a non-functional thyroid nodule, the nodule was found to be hot in the postoperative phase of TSH suppression. By focusing on the atypical postoperative course of the TSHoma, we were able to conclude that this was a case of TSHoma combined with an autonomously functioning thyroid nodule (AFTN). LEARNING POINTS: The diagnosis of autonomously functioning thyroid nodules (AFTNs) depends on suppressed serum TSH levels. If thyroid hormones are resistant to somatostatin analogue therapy or surgery for TSHoma, complications of AFTN as well as destructive thyroiditis need to be considered. It is important to revisit the basics when facing diagnostic difficulties and not to give up on understanding the pathology.
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ATP, used in cells as an energy currency, also acts as an extracellular signaling molecule. Studies of purinergic receptor subtypes have revealed that purinergic chemical transmission plays important roles in various cell types. The vesicular nucleotide transporter (VNUT), the ninth transporter in the SLC17 organic anion transporter family, is essential for vesicular ATP storage and its subsequent release. The VNUT is localized on the membrane of secretory vesicles and actively transports ATP into vesicles using an electrochemical gradient of protons supplied by vacuolar proton ATPase (V-ATPase) as a driving force. ATP acts as a damage-associated molecular pattern (DAMPs), contributing to the persistence of chronic inflammation. Chronic inflammation induces systemic insulin resistance, which is the underlying pathology of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). We previously demonstrated that ATP transported in insulin granules via the VNUT negatively regulates insulin secretion. We also found that hepatocytes release ATP in a VNUT-dependent manner, which elicits hepatic insulin resistance and inflammation. VNUT-knockout mice exhibited improved glucose tolerance and were resistant to the development of high fat diet-induced NAFLD. In this article, we summarize recent advances in our understanding of the mechanism of the VNUT, the development of inhibitors, and its pathological involvement in type 2 diabetes and NAFLD. The pharmacological inhibition of the VNUT may represent a potential therapeutic approach for the treatment of metabolic diseases.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Terapia de Alvo Molecular , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas de Transporte de Nucleotídeos/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Ácido Clodrônico/farmacologia , Ácido Clodrônico/uso terapêutico , Descoberta de Drogas , Humanos , Resistência à Insulina/genética , Secreção de Insulina/genética , Camundongos Knockout , Proteínas de Transporte de Nucleotídeos/antagonistas & inibidores , Vesículas Secretórias/metabolismoRESUMO
The vesicular nucleotide transporter (VNUT) is responsible for the vesicular storage and release of ATP from various ATP-secreting cells, and it plays an essential role in purinergic signaling. Although extracellular ATP and its degradation products are known to mediate various inflammatory responses via purinoceptors, whether vesicular ATP release affects steatohepatitis and acute liver injury is far less understood. In the present study, we investigated the effects of clodronate, a potent and selective VNUT inhibitor, on acute and chronic liver inflammation in mice. In a model of methionine/choline-deficient diet-induced non-alcoholic steatohepatitis (NASH), the administration of clodronate reduced hepatic inflammation, fibrosis, and triglyceride accumulation. Clodronate also protected mice against high-fat/high-cholesterol diet-induced steatohepatitis. Moreover, prophylactic administration of clodronate prevented D-galactosamine and lipopolysaccharide-induced acute liver injury by reducing inflammatory cytokines and hepatocellular apoptosis. In vitro, clodronate inhibited glucose-induced vesicular ATP release mediated by VNUT and reduced the intracellular level and secretion of triglycerides in isolated hepatocytes. These results suggest that VNUT-dependent vesicular ATP release plays a crucial role in the recruitment of immune cells, cytokine production, and the aggravation of steatosis in the liver. Pharmacological inhibition of VNUT may provide therapeutic benefits in liver inflammatory disorders, including NASH and acute toxin-induced injury.
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Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácido Clodrônico/farmacologia , Fígado Gorduroso/tratamento farmacológico , Proteínas de Transporte de Nucleotídeos/genética , Trifosfato de Adenosina/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Dieta/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Proteínas de Transporte de Nucleotídeos/antagonistas & inibidores , Receptores Purinérgicos/genéticaRESUMO
Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (ß-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear ß-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous ß-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear ß-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear ß-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.
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Biomarcadores Tumorais/análise , Craniofaringioma/diagnóstico , Imuno-Histoquímica/métodos , Neoplasias Hipofisárias/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Craniofaringioma/genética , Craniofaringioma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Adulto Jovem , beta Catenina/genéticaRESUMO
Non-alcoholic steatohepatitis (NASH) is becoming a growing public health problem along with the increase of metabolic syndrome worldwide. Extracellular nucleotides are known to serve as a danger signal by initiating purinergic signaling in many inflammatory disorders, although the role of purinergic signaling in the progression of NASH remains to be clarified. Vesicular nucleotide transporter (VNUT) is a key molecule responsible for vesicular ATP release to initiate purinergic signaling. Here, we studied the role of VNUT in the progression of nonalcoholic steatohepatitis. VNUT was expressed in mouse hepatocytes and associated, at least in part, with apolipoprotein B (apoB)-containing vesicles. High glucose stimulation evoked release of appreciable amount of ATP from hepatocytes, which disappeared in hepatocytes of Vnut knockout (Vnut-/-) mice. Glucose treatment also stimulated triglyceride secretion from hepatocytes, which was inhibited by PPADS and MRS211, antagonists of P2Y receptors, and clodronate, a VNUT inhibitor, and was significantly reduced in Vnut-/- mice. In vivo, postprandial secretion of triglyceride from hepatocytes was observed, while the serum triglyceride level was significantly reduced in Vnut-/- mice. On a high-fat diet, the liver of wild type mice exhibited severe inflammation, fibrosis, and macrophage infiltration, which is similar to NASH in humans, while this NASH pathology was not observed in Vnut-/- mice. These results suggest that VNUT-mediated vesicular ATP release regulates triglyceride secretion and involves in chronic inflammation in hepatocytes. Since blockade of vesicular ATP release protects against progression of steatohepatitis, VNUT may be a pharmacological target for NASH.
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Trifosfato de Adenosina/metabolismo , Hepatócitos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismo , Animais , Transporte Biológico , Células Cultivadas , Progressão da Doença , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
In recent years, the role ofimmune checkpoint inhibitors(ICIs)has become crucial in cancer therapy. However, ICIs are known to trigger a wide variety of autoimmune side effects, termed immune-related adverse events(irAEs), which can influence multiple organs. Hypophysitis induced by ICIs, which is defined as the inflammation of the pituitary gland and is the cause ofhypopituitarism, is one ofthe important toxicities, because it can be life-threatening event when it is not diagnosed or managed properly. Therefore, ICIs-induced hypophysitis should be recognized as one ofthe oncologic emergencies. Symptoms, laboratory data, hormone level measurement, and pituitary magnetic resonance imaging are necessary for diagnosis. It should be taken into consideration that types of agents in ICIs have an effect on patterns of symptoms, onset timing, and hormone deficiencies. Replacement of appropriate hormones according to severity is fundamental strategy. Patient education especially about sick day rules is vital, because adrenal insufficiency secondary to adrenocorticotropic hormone deficiency usually remains permanently. There is no established predictive biomarker for irAEs yet. Thus, for an early awareness of the symptoms ofirAEs and a proper management in clinical practice, interprofessional collaboration among oncologists, endocrinologists, nurses, pharmacists, and other health care workers must be essential.
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Hipopituitarismo , Doenças do Sistema Endócrino , HumanosRESUMO
Pituitary adenoma has been reported to be detectable in only 36-63% of Cushing's disease (CD) patients by magnetic resonance imaging (MRI). In this study, we investigate the outcomes and problems associated with tumor identification using 3-Tesla (3-T) MRI, which provides clearer images than ≤1.5-T MRI, in 115 patients who were initially diagnosed with CD. Before surgery, 31 macroadenomas (27%) and 54 microadenomas (47%) were identified by 3-T MRI, but pituitary adenoma was invisible on MRI in the remaining 30 cases (26%). The smallest tumor diameter amenable to a definitive diagnosis was 2 mm, and spoiled gradient-echo was the best sequence for diagnosing microadenomas. In 14 of 30 cases of MRI-invisible CD, the pituitary adenoma was identified during surgery. Nine of these 14 tumors that developed from outside the pituitary gland were retrospectively identified on MRI by comparison with surgical findings. The remaining 16 cases of MRI-invisible CD in which the pituitary adenoma was not identified during surgery involved partial hypophysectomy. Seven cases were hormonally remitted, but another nine cases experienced persistent disease after surgery. The sensitivity and specificity of the pituitary adenoma diagnosis in CD patients after the introduction of 3-T MRI were 80% and 100%, respectively. However, the sensitivity decreased to 72% when macroadenomas were excluded. Some adenomas associated with CD are still undetectable on 3-T MRI due to tumor size, location and intensity. However, sensitivity can be improved by monitoring tumors that develop outside the pituitary gland.
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Adenoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Adenoma/complicações , Humanos , Hipersecreção Hipofisária de ACTH/etiologia , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Multidrug-resistant Pseudomonas aeruginosa (MDRP), defined as Pseudomonas aeruginosa resistant to aminoglycosides, carbapenems, and fluoroquinolones, has emerged as an increasingly problematic cause of hospital-acquired infection. With parenteral colistin unavailable in Japan, effective antimicrobial options are severely limited. We report a case of MDRP bacteremia successfully treated with antibiotic combination therapy screened by a 'Break-point Checkerboard Plate'. A 54-year-old man with malignant lymphoma who became febrile 9 days after a recent course of chemotherapy had a neutrophil count of 176/microL. Treatment with meropenem and vancomycin was ineffective and high fever persisted. Methicillin-resistant Staphylococcus aureus (MRSA) and MDRP were isolated from blood culture and combination therapy with aztreonam and amikacin was selected for MDRP based on 'Break-point Checkerboard Plate' results. Linezolid was used for MRSA. The patient recovered successfully from MDRP and MRSA sepsis.