Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

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.

Perirenal fat thickness is a powerful predictor for surgical outcomes of transperitoneal laparoscopic adrenalectomy.

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.

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

CONTEXT: Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE: To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS: This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS: The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION: To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis.

Among the side effects of methimazole (MMI) for the treatment of Graves' disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves' disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.

Pasireotide-resistant Refractory Cushing's Disease without Somatostatin Receptor 5 Expression.

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.

[VNUT Is a Therapeutic Target for Type 2 Diabetes and NASH].

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.

GH-induced LH hyporesponsiveness as a potential mechanism for hypogonadism in male patients with acromegaly.

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.

Challenges in the functional diagnosis of thyroid nodules before surgery for TSH-producing pituitary adenoma.

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.

Clodronate, an inhibitor of the vesicular nucleotide transporter, ameliorates steatohepatitis and acute liver injury.

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.

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?

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.

Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis.

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.

Correction to: Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

[This corrects the article DOI: 10.1186/s13030-020-00186-8.].

Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) is a disease resulting in extreme weight loss. It is caused by multiple factors, including psychosocial, environmental, and genetic factors. A genetic abnormality affecting lipid metabolism has been recently reported in patients with AN. However, it is unknown whether lipid metabolism abnormalities in AN are caused by eating behavior, undernutrition, and/or genetic factors. The meaning of lipid metabolism in AN remains unclear. In particular, differences in the profiles of very long-chain fatty acids (VLCFAs) in patients with various types of AN have not been studied. This study aimed to determine changes to the fatty acid profile over a 3-month period, specifically that of long-chain fatty acids (LCFAs) and VLCFAs in patients with various types of AN. METHODS: We evaluated 69 female patients with AN, subclassified as AN-restricting type (AN-R) and AN-Binge-Eating/Purging type (AN-BP). On admission and after 3 months of treatment, height, weight, body mass index, plasma and serum parameters, and plasma fatty acid concentrations were measured in all patients. The control group included 25 healthy, age-matched women. Comparisons between the groups were made using one-way ANOVA, while those between the various parameters at admission and after 3 months within each group were made using the Wilcoxon signed rank test. RESULTS: On admission, the AN-R and the AN-BP groups had significantly higher levels of 18-24C and > 14C fatty acids (LCFAs and VLCFAs, respectively) than the control group. After 3 months of treatment, both groups showed high levels of 14-24C fatty acids. The levels of VLCFAs (C22:0 and C24:0) and LCFA (C18:3) after 3 months of treatment remained high in both AN groups relative to the control group. CONCLUSIONS: Eating behaviors appear to be associated with levels of LCFAs. Lipid metabolism abnormalities under conditions of starvation in AN might have a genetic basis and appear to be associated with VLCFA (C22:0 and C24:0) and LCFA (C18:3) levels.

[Hypopituitarism].

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.

Outcomes of three-Tesla magnetic resonance imaging for the identification of pituitary adenoma in patients with Cushing's disease.

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.

Portal hypertension in prolonged anorexia nervosa with laxative abuse: A case report of three patients.

OBJECTIVE: There has been no report on portal hypertension related to anorexia nervosa (AN). METHOD: We describe three cases of portal hypertension manifesting with collateral circulation represented by gastroesophageal varices in prolonged AN with laxative abuse and self-vomiting. These women, in their 20s to 50s, were diagnosed as having AN binging and purging type (AN-BP) that included self-induced vomiting and abuse of irritating laxatives (more than 100 tablets daily). RESULTS: Case 1 showed prominent ascites and a gastro-renal shunt on computed tomography scanning. Case 2 showed gastroesophageal varices on endoscopic examination. Case 3 showed gastroesophageal varices on computed tomography scanning and endoscopic examination. We performed liver biopsies in all patients and found only slight pericellular fibrosis. Our patients showed typical symptoms of portal hypertension, although liver cirrhosis was not present. DISCUSSION: We speculated that abnormal eating and purging behaviors were involved in the development of portal hypertension. We hypothesized that long-term laxative abuse, dehydration, and abnormal eating behavior are involved in the development of portal hypertension, considering these were common features in our patients. Portal hypertension and gastroesophageal varices should be considered as one of the potentially existing complications in prolonged AN-BP with self-induced vomiting and abuse of irritating laxatives.

Correction to: Purging behaviors relate to impaired subjective sleep quality in female patients with anorexia nervosa: a prospective observational study.

[This corrects the article DOI: 10.1186/s13030-017-0107-7.].

Purging behaviors relate to impaired subjective sleep quality in female patients with anorexia nervosa: a prospective observational study.

BACKGROUND: We examined how purging behaviors relate to subjective sleep quality and sleep patterns and how symptoms of disordered eating behaviors relate to global sleep quality in female patients with anorexia nervosa (AN). METHODS: Participants were new consecutive female inpatients with a primary diagnosis of AN admitted to the Department of Psychosomatic Medicine at Kohnodai Hospital between June 26 and December 25, 2015. We recorded patients' habitual eating behaviors, laxative overuse, or uretic misuse, and administered the Japanese versions of the Pittsburgh Sleep Quality Index (PSQI-J) and Center for Epidemiologic Studies Depression Scale. Raw PSQI-J data were used to determine sleep patterns (sleep-onset time, wake-up time, and sleep duration). To examine how purging behaviors related to sleep quality, we compared variables between AN restricting type (ANr) and AN binge-eating/purging type (ANbp). Spearman's rank correlation analysis was used to examine which potential factors influence global PSQI-J score. RESULTS: Participants were 20 patients, of whom 12 had ANbp. Two ANr patients (25%) had global PSQI-J scores greater than 5, compared to 9 ANbp patients (75%; P < 0.05). Circadian rhythm disruption and abnormal sleep duration were significantly greater in ANbp patients than in ANr patients (P < 0.05). Global PSQI-J was significantly correlated with a diagnosis of ANbp (ρ = 0.525; P < 0.05), vomiting (ρ = 0.561; P < 0.05), and duration of illness (ρ = 0.536; P < 0.05). CONCLUSIONS: ANbp patients had worse global sleep quality and greater disrupted sleep than did ANr patients. This suggests that treatments focusing on sleep would be useful, especially for ANbp patients. Furthermore, vomiting and duration of illness should be considered essential factors related to impaired global sleep quality. TRIAL REGISTRATION: Not applicable.

Three cases of appendicitis with anorexia nervosa under inpatient care.

BACKGROUND: Little is known about the occurrence of appendicitis during the re-nourishment period in anorexia nervosa (AN). We report three cases of appendicitis in patients with AN that occurred after hospitalization for treatment of AN. CASE PRESENTATION: Case 1 is a 34-year-old female, case 2 is a 17-year-old female and case 3 is a 38-year-old female. Constipation was observed in all three cases. Careful management of defecation might be essential to prevent appendicitis among AN patients during the re-nourishment period under inpatient care. In addition, mild and diffuse symptoms were observed in all three cases. Therefore, diagnosis proved to be difficult to make and abdominal computed tomography was particularly helpful in all cases. As the symptoms were diffuse, the condition of appendicitis turned out to be more severe and complicated in one case. Additionally, the incidence of appendicitis in AN in the current study might be higher than that in the normal population. CONCLUSIONS: These findings suggest that appendicitis should be considered as one of the potentially important complications in the therapy for AN.

Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration.

AIM/HYPOTHESIS: Mitochondria and the endoplasmic reticulum (ER) physically interact by close structural juxtaposition, via the mitochondria-associated ER membrane. Inter-organelle communication between the ER and mitochondria has been shown to regulate energy metabolism and to be central to the modulation of various key processes such as ER stress. We aimed to clarify the role of mitochondrial fission in this communication. METHODS: We generated mice lacking the mitochondrial fission protein dynamin-related protein 1 (DRP1) in the liver (Drp1LiKO mice). RESULTS: Drp1LiKO mice showed decreased fat mass and were protected from high-fat diet (HFD)-induced obesity. Analysis of liver gene expression profiles demonstrated marked elevation of ER stress markers. In addition, we observed increased expression of the fibroblast growth factor 21 (FGF21) gene through induction of activating transcription factor 4, master regulator of the integrated stress response. CONCLUSIONS/INTERPRETATION: Disruption of mitochondrial fission in the liver provoked ER stress, while inducing the expression of FGF21 to increase energy expenditure and protect against HFD-induced obesity.