ABSTRACT
OBJECTIVE: We analyzed robotic partial nephrectomy (RPN) outcomes in obese patients based on body mass index (BMI) and trifecta achievement. METHODS: We retrospectively reviewed 296 patients who underwent RPN at Kansai Medical University Hospital between 2014 and 2022. The preoperative clinical data and perioperative outcomes were evaluated. Trifecta achievement (negative surgical margin, no major complications, and no acute kidney injury on postoperative day three) and its relationship to three BMI groups (<25, 25 to <30, and ≥30) were the primary outcome. The correlation between factors in achieving trifecta and BMI was evaluated. Univariate and multivariate analyses assessed variables for achieving the trifecta with logistic regression analysis. C-statistics quantitatively evaluated the prediction accuracy. RESULTS: Among 296 patients, 264 (89.2%) achieved trifecta (BMI categories were <25 [89.9%], 25 to <30 [89.4%], and ≥30 [82.6%]). There was no significant BMI-related difference (p = 0.566). Intraoperative blood loss increased with the BMI (p = 0.034). Multivariate analyses showed preoperative aspects and dimensions used for anatomic (PADUA) score independently predicted trifecta failure (odds ratio 1.71; 95% confidence interval 1.32-2.20; p < 0.001). The C-statistics of the PADUA score increased with increasing BMI. CONCLUSIONS: Higher BMI patients had more intraoperative blood loss during RPN. However, RPN remains safe and has acceptable quality and functional outcomes. Since patients with high PADUA scores combined with a high BMI may be at risk of trifecta failure, this should be explained before RPN.
ABSTRACT
Imaging is useful in identifying the primary site of an unknown primary cancer, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an excellent imaging modality for identifying the primary lesion. However, a potential limitation is that 18F-FDG is physiologically excreted from the kidneys, thus masking renal lesions. In this report, we describe two cases of cancer of unknown origin that were detected as originating from renal cancer on 18F-FDG PET/CT. Both cases showed abnormal nodular accumulation of 18F-FDG in the kidney, which can be distinguished from the physiological excretion of 18F-FDG in the urinary tract. It is clinically crucial to be able to confirm the possibility of renal cancer, and careful observation of the urinary tract with 18F-FDG PET/CT can be useful.
ABSTRACT
Background: Surgery for pheochromocytoma and paraganglioma (PPGL) can lead to life-threatening complications, such as intraoperative hypertensive crises, even when adequate doses of preoperative α-receptor blockades are administered. Objectives: The aim of this study was to identify preoperative factors associated with intraoperative maximum arterial pressure (AP) in patients with PPGL. Methods: We retrospectively reviewed the cases of 61 PPGL patients who underwent surgical resection in our hospital between 2006 and 2020. The primary outcome was intraoperative maximum AP as a single index for continuous variables. Simple and multiple linear regression model were used for statistical analysis. Results: The median maximum systolic AP during surgery was 165 mmHg (interquartile range: 150 - 180 mmHg). Log24-h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) was correlated with intraoperative maximum AP (R-squared = 0.218, P < 0.001). Multiple regression analyses showed that diabetes mellitus, one or more of the classic triad, and log24-h urinary-fractionated MN and NMN were independent factors associated with intraoperative maximum AP. Conclusions: Patients with PPGL accompanied by diabetes mellitus, one or more of the classic triad, and high log 24-h urinary-fractionated MN and NMN values may be at risk for hypertensive crises during surgery regardless of whether preoperative α-receptor blockades are used. Clinicians should manage these patients more carefully and effectively.
ABSTRACT
Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic ß-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings.
ABSTRACT
Adrenal cortex autotransplantation with ACTH stimulation may be an alternative therapy for patients with bilateral adrenalectomy to avoid adrenal crisis, but its underlying mechanism has not been elucidated. Previously, we detected Dhh upregulation in rat adrenocortical autografts after transplantation. Here, we investigated potential regulators such as Gata4, Gata6, Sry and Sox9 which affect Dhh transcription in adrenocortical autografts with or without ACTH stimulation. In ACTH-stimulated autografts, Gata4 and Gata6 were downregulated compared to control autografts. This response was linked to rDhh repression. A reporter assay using the upstream region of rDhh and a GATA binding motif revealed that rDhh promoters were significantly upregulated by co-transfection with Gata4 or Gata6 or both. Sry and Sox9 expression in autografts with or without ACTH stimulation were verified by PCR and RNAscope analyses. The ovarian differentiation factors Foxl2 and Rspo1 were also upregulated in the autografts. Gata4 and Gata6 were found to be significant factors in the regulation of rDhh expression and could be associated with adrenocortical autograft maintenance. Gonadal primordia with bipotential testicular and ovarian functions may also be present in these autografts.
Subject(s)
Adrenal Cortex/metabolism , Adrenal Cortex/surgery , GATA4 Transcription Factor/metabolism , GATA6 Transcription Factor/metabolism , Hedgehog Proteins/genetics , Adrenal Cortex/drug effects , Adrenal Cortex/physiology , Adrenocorticotropic Hormone/pharmacology , Animals , Rats , Regeneration/drug effects , Transplantation, Autologous , Up-Regulation/drug effectsABSTRACT
SUMMARY: A 21-year-old woman was referred to our hospital to treat bilateral pheochromocytomas (PCCs) after a diagnosis of multiple endocrine neoplasia type 2A (MEN2A). We performed bilateral laparoscopic adrenalectomy. One year after the operation, urinary fractionated metanephrines in 24-h urine increased. MRI showed a 30 mm tumor on the interaortocaval region and 123I-MIBG concentrated in this area. We excised the tumor and performed para-aortic lymphadenectomy. Histopathologic examination confirmed a PCC arising from ectopic adrenal tissue. Urinary fractionated metanephrines in 24-h urine declined to basal levels immediately after the operation. We detected no recurrence of paraganglioma or PCC for 5 years after the treatment. LEARNING POINTS: Most ectopic adrenal tissue is associated with no symptoms and contains only the adrenal cortex. Adrenocortical tumors sometimes arise from ectopic adrenal tissues similarly to in the normal adrenal gland. PCC arising from ectopic adrenal tissue occurs infrequently. MEN2-related PCC is accompanied by adrenal medullary hyperplasia, which might be part of tumorigenesis.
ABSTRACT
The hypocretin/orexin neuropeptide system coordinates the regulation of various physiological processes. Our previous study reported that a reduction in the expression of pleomorphic adenoma genelike 1 (Plagl1), which encodes a C2H2 zincfinger transcription factor, occurs in hypocretin neuronablated transgenic mice, suggesting that PLAGL1 is coexpressed in hypocretin neurons and regulates hypocretin transcription. The present study examined whether canonical preprohypocretin transcription is functionally modulated by PLAGL1. Double immunostaining indicated that the majority of hypocretin neurons were positive for PLAGL1 immunoreactivity in the nucleus. Notably, PLAGL1 immunoreactivity in hypocretin neurons was altered in response to several conditions affecting hypocretin function. An uneven localization of PLAGL1 was detected in the nuclei of hypocretin neurons following sleep deprivation. Chromatin immunoprecipitation revealed that endogenous PLAGL1 may bind to a putative PLAGL1binding site in the proximal region of the hypocretin gene, in the murine hypothalamus. In addition, electroporation of the PLAGL1 expression vector into the fetal hypothalamus promoted hypothalamic hypocretin transcription. These results suggested that PLAGL1 may regulate hypothalamic hypocretin transcription.
Subject(s)
Cell Cycle Proteins/metabolism , Orexins/genetics , Transcription Factors/metabolism , Transcription, Genetic , Animals , Base Sequence , Embryo, Mammalian/cytology , Genes, Tumor Suppressor , Hypothalamus/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , NIH 3T3 Cells , Promoter Regions, Genetic/genetics , Protein BindingABSTRACT
Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and glucocorticoid replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. A remarkable renewal in cell proliferation and increase in Cyp11b1, which encodes 11-beta-hydroxylase, occurred in adrenocortical autografts from 2-3 weeks after autotransplantation. Serum corticosterone and adrenocorticotropic hormone levels were almost recovered to sham level at 4 weeks after autotransplantation. The adrenocortical autografts showed increased Dhh expression at 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule at 3 weeks after autotransplantation. Dhh and Gli1 might function in concert to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.
Subject(s)
Adrenal Glands/physiology , Hedgehog Proteins/metabolism , Regeneration , Zinc Finger Protein GLI1/metabolism , Adrenal Glands/cytology , Adrenal Glands/transplantation , Animals , Autografts , Cell Proliferation , Male , Rats , Rats, Wistar , Signal TransductionABSTRACT
Adrenal corticotropin (ACTH) -independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is the treatment of choice, but lifetime steroid replacement is essential. Here we report a case of AIMAH whose hyperglycemia was improved following unilateral adrenalectomy. A 42-year-old woman with serious intellectual disability and intractable epilepsy presented with polydipsia. Casual blood glucose and hemoglobin A1c (HbA1c) were 322 mg/dl and 8.5%, respectively. The cortisol level was high and ACTH level was low. Abdominal computed tomography and magnetic resonance imaging revealed unsuspected macronodular enlargement of bilateral adrenal glands (left 8 cm, right 4 cm in maximal diameter) and she was diagnosed with AIMAH. Both adrenal glands showed intense 131 I-adosterol accumulation predominantly in the left side and left-unilateral laparoscopic adrenalectomy was performed. Both insulin and oral antidiabetic drugs could be cancelled postoperatively, and HbA1c decreased to 5.7%. Steroid was not replaced but she never experienced adrenal crisis. We conclude that unilateral adrenalectomy is a safe and effective treatment for certain cases of AIMAH.
Subject(s)
Cushing Syndrome/surgery , Adrenalectomy , Adult , Female , Humans , Magnetic Resonance Imaging , Treatment OutcomeABSTRACT
Patients with bilateral pheochromocytoma often require an adrenalectomy. Autotransplantation of the adrenal cortex is an alternative therapy that could potentially be performed instead of receiving glucocorticoid replacement following adrenalectomy. Adrenal cortex autotransplantation aims to avoid the side effects of longterm steroid treatment and adrenal insufficiency. Although the function of the hypothalamohypophysial system is critical for patients who have undergone adrenal cortex autotransplantation, the details of that system, with the exception of adrenocorticotropic hormone in the subjects with adrenal autotransplantation, have been overlooked for a long time. To clarify the precise effect of adrenal autotransplantation on the pituitary gland and hypothalamus, the current study examined the gene expression of hormones produced from the hypothalamus and pituitary gland. Bilateral adrenalectomy and adrenal autotransplantation were performed in 8 to 9weekold male rats. The hypothalamus and pituitary tissues were collected at 4 weeks after surgery. Transcriptional regulation of hypothalamic and pituitary hormones was subsequently examined by reverse transcriptionquantitative polymerase chain reaction. Proopiomelanocortin, glycoprotein hormone α polypeptide, and thyroid stimulating hormone ß were significantly elevated in the pituitary gland of autotransplanted rats when compared with shamoperated rats. In addition, there were significant differences in the levels of corticotropin releasing hormone receptor 1 (Crhr1), Crhr2, nuclear receptor subfamily 3 group C member 1 and thyrotropin releasing hormone receptor between the shamoperated rats and autotransplanted rats in the pituitary gland. In the hypothalamus, corticotropin releasing hormone and urocortin 2 mRNA was significantly upregulated in autotransplanted rats compared with shamoperated rats. The authors identified significant alterations in the function of not only the hypothalamuspituitaryadrenal axis, but also the adenohypophysis thyrotropes in autotransplanted rats. In the future, it will be important to examine other tissues affected by glucocorticoids following adrenal cortex autotransplantation.
Subject(s)
Adrenal Cortex/transplantation , Hypothalamo-Hypophyseal System/metabolism , Adrenalectomy , Animals , Corticotropin-Releasing Hormone/genetics , Corticotropin-Releasing Hormone/metabolism , Glycoprotein Hormones, alpha Subunit/genetics , Glycoprotein Hormones, alpha Subunit/metabolism , Hypothalamus/metabolism , Male , Pituitary Gland/metabolism , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Corticotropin-Releasing Hormone/metabolism , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Receptors, Thyrotropin-Releasing Hormone/genetics , Receptors, Thyrotropin-Releasing Hormone/metabolism , Thyrotropin, beta Subunit/genetics , Thyrotropin, beta Subunit/metabolism , Transplantation, Autologous , Up-Regulation , Urocortins/genetics , Urocortins/metabolismABSTRACT
Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy.
Subject(s)
Hypothalamus/immunology , Hypothalamus/metabolism , Inflammation , Lipopolysaccharides/pharmacology , Orexins/metabolism , Sleep/immunology , Wakefulness , Animals , Ataxin-3/metabolism , Gene Expression , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Lipopolysaccharides/administration & dosage , Male , Mice , Mice, TransgenicABSTRACT
Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non-steroidal anti-inflammatory drugs, anti-allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase-2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase-2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase-2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.
Subject(s)
Cyclooxygenase 2 Inhibitors/therapeutic use , Cystitis/diet therapy , Humans , ImmunohistochemistryABSTRACT
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0-2 points), moderately differentiated (MD, 3-6 points) and poorly differentiated (PD, 7-10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08±0.17 and 5.33±0.43 (mean±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=-0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5±2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.