A rare case of plexiform neurofibroma of the liver in a patient without neurofibromatosis type 1.

Plexiform neurofibroma is mainly associated with neurofibromatosis type 1 and is seldom observed in the liver. Its occurrence in the liver without neurofibromatosis type 1 is even rarer. We report an extremely rare case of plexiform neurofibroma of the liver diagnosed by laparoscopic biopsy in a patient without neurofibromatosis type 1. The patient was a 35-year-old man who had neither clinical signs nor any family history of neurofibromatosis type 1. Abdominal ultrasonography, as part of a health screening, had detected a hepatic tumor. Subsequent contrast ultrasonography, computed tomography, and magnetic resonance imaging showed the tumor extending from the retroperitoneal space around the aorta to the hepatic hilum and distal portal branches in the right hepatic lobe, gallbladder, and left hepatic lobe. 18F-fluorodeoxyglucose positron emission tomography showed no abnormal accumulation. Histopathological examination of the tumor obtained laparoscopically led to a diagnosis of plexiform neurofibroma. Because the patient was asymptomatic with no features of malignancy, he was only monitored and managed. At follow-up 10 years later, computed tomography showed a decrease in tumor size. It is important to recognize that, while rare, plexiform neurofibroma can occur without neurofibromatosis type 1. We recommend follow-up instead of unreasonable surgery in such cases.

Usefulness of "Nelaton Attachment" for endoscopic submucosal dissection of colorectal neoplasms.

Background and study aims Although colorectal endoscopic submucosal dissection (ESD) has enabled high en bloc resection rates regardless of tumor size, colorectal ESD is still a challenging procedure. We developed a novel device called the Nelaton Attachment, which allows endoscopists to manipulate the ESD knives using two fingers of their left hand while holding the endoscope with their right hand. We retrospectively investigated the efficacy and safety of the Nelaton Attachment for colorectal ESD. We compared efficacy and safety between Nelaton Attachment and non-Nelaton Attachment groups, and also conducted an ex vivo experiment to evaluate the effect of the Nelaton Attachment. Patients and methods We retrospectively reviewed 36 consecutive patients with 37 colorectal tumors who had undergone ESD at Kishiwada Tokushukai Hospital and Naritatomisato Tokushukai Hospital between April 2016 and September 2018. The Nelaton Attachment was used for 22 of the 37 colorectal ESDs. In the ex vivo experiment, endoscopists inserted and withdrew an ESD knife 2 cm using two fingers of their left hand with and without the Nelaton Attachment. Results Median procedure time was significantly shorter in the Nelaton Attachment group (38 min [range 6 - 195 min]) compared to the non-Nelaton Attachment group (75 min [range 17 - 198 min]; P  = 0.030). Median time to complete the ex vivo experiment five times was significantly faster with the Nelaton Attachment than without the Nelaton Attachment ( P  = 0.001). Conclusions Use of the Nelaton Attachment for colorectal ESD is feasible and safe, and may facilitate colorectal ESD procedures.

[A Case of Advanced Gastric Cancer with Liver Metastases Treated with Curative Conversion Therapy after S-1 plus Oxaliplatin].

An 81-year-old man was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 2 tumor in the antrum of the stomach. The histopathological findings showed a moderately differentiated HER2-negative adenocarcinoma. Two low-density areas of 17mm and 26mm in diameter were observed in the liver S6 and S8respectively at the CT scan. Nine courses of S-1 plus oxaliplatin(SOX)therapy were administered to this patient with gastric cancer and liver metastases. Since both the primary tumor and the liver metastases were significantly reduced by the chemotherapy, distal gastrectomy(D2 dissection)and partial liver resection(liver S6, S8)were performed. The histopathological findings revealed no tumor cells in the primary tumor, lymph nodes, and liver metastases, with a histologic effect of Grade 3. The patient underwent adjuvant therapy with S-1. He has been alive without recurrence for 11 months post-surgery.

Medical Treatment of Postendoscopic Submucosal Dissection Phlegmonous Gastritis in an Elderly Diabetic Woman with Myelodysplastic Syndrome.

Phlegmonous gastritis is a rare, suppurative disease characterized by full-thickness exudative changes, infiltration of inflammatory cells, and edema primarily in the submucosal layer. A 76-year-old woman with type 2 diabetes and myelodysplastic syndrome underwent endoscopic submucosal dissection (ESD) for early gastric cancer. Postoperatively, she developed persistent fever and computed tomography displayed full-circumference thickening of the gastric wall and increased levels of fat stranding. Endoscopy showed post-ESD ulcer floor expansion, formation of a false lumen between the ulcer floor and surrounding folds, and adhesion of purulent matter. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were detected from pus culture and Klebsiella pneumoniae from blood culture, leading to a diagnosis of phlegmonous gastritis. Contrast examination showed no leakage outside the gastric wall; therefore, the patient fasted and was given antibiotics. She was successfully treated with medical therapy, as demonstrated by repeat endoscopy. Based on our experience, we recommend antibiotics before and after ESD in patients thought to be at high risk of infection, as well as careful postoperative management including postoperative endoscopy.

Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in Patients with Type 2 Diabetes Mellitus: A Cohort Study.

INTRODUCTION: Previous studies have shown that serum bilirubin concentration is inversely associated with the risk of cardiovascular disease. The relationship between serum bilirubin concentration and left ventricular geometry, however, has not been investigated in patients with diabetes mellitus. METHODS: In this cohort study, 158 asymptomatic patients with type 2 diabetes mellitus without overt heart disease were enrolled. Left ventricular structure and function were assessed using echocardiography. Serum bilirubin concentration, glycemic control, lipid profile, and other clinical characteristics were evaluated, and their association with left ventricular geometry was determined. Patients with New York Heart Association Functional Classification greater than I, left ventricular ejection fraction less than 50%, history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, or creatinine clearance less than 30 ml/min, and those receiving insulin treatment, were excluded. RESULTS: Univariate analyses showed that relative wall thickness (RWT) was significantly correlated with diastolic blood pressure (P = 0.003), HbA1c (P = 0.024), total cholesterol (P = 0.043), urinary albumin (P = 0.023), and serum bilirubin concentration (P = 0.009). There was no association between left ventricular mass index and serum bilirubin concentration. Multivariate linear regression analysis showed that log RWT was positively correlated with diastolic blood pressure (P = 0.010) and that log RWT was inversely correlated with log bilirubin (P = 0.003). In addition, the patients with bilirubin less than 0.8 mg/dl had a higher prevalence of concentric left ventricular remodeling compared with those with bilirubin 0.8 mg/dl or more. CONCLUSION: Our study shows that the serum bilirubin concentration may be associated with the progression of concentric left ventricular remodeling in patients with type 2 diabetes mellitus.

Syndrome of inappropriate antidiuretic hormone secretion in a case of olfactory neuroblastoma without anti-diuretic hormone immunoreactivity: A case report and review of the literature.

Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.

[A case of paralytic ileus associated with varicella zoster virus infection].

A 79-year-old woman with a history of pyothorax was admitted with a 4-day history of abdominal distension. Physical examination revealed marked abdominal distention, absent bowel sounds, and a vesicular rash over the left Th8-10 dermatome. Abdominal radiography showed gaseous distension of the colon and ileum. Colonoscopy excluded any obstructive process of the colon. Laboratory findings yielded positive results for serum IgM and IgG against the varicella zoster virus (VZV) . Paralytic ileus associated with the VZV was therefore diagnosed. The ileus improved after conservative treatment with intravenous acyclovir. Although shingles is frequently encountered, it is a rare cause of paralytic ileus. In the future, the VZV should be considered as one of the causes of paralytic ileus, and complete resolution can be achieved with conservative management.

[A case of primary biliary cirrhosis with systemic lymph node enlargement].

A 40's woman was hospitalized with cervical lymph node enlargement. Laboratory examinations showed elevated serum bile duct enzymes and the presence of anti-mitochondrial antibody. Abdominal ultrasonography and computed tomography showed enlargement of not only perihepatic lymph nodes, but also axillary and cervical lymph nodes. FDG-PET showed intense uptake concordant with these lymph nodes. We performed endoscopic ultrasonographic fine-needle aspiration biopsy of a perihepatic lymph node, but detected no malignant cells. We then performed liver biopsy, and obtained a histological diagnosed primary biliary cirrhosis. Systemic lymph nodes decreased together with serum bile duct enzyme levels during treatment with ursodeoxycholic acid.

[A case of autoimmune pancreatitis with multifocal mass lesions].

We present a case of a 73-year-old man with multifocal autoimmune pancreatitis (AIP) in the pancreatic head and tail, and who had undergone sigmoidectomy and rectectomy 28 months before presenting to our department. Upon presentation, his serum IgG4 level was elevated at 267mg/dl, but tumor marker levels were within normal ranges. CT and MRI showed two localized pancreatic masses with delayed enhancement, but endoscopic retrograde pancreatography revealed neither stenosis nor dilatation of the main pancreatic duct. FDG-PET examination showed intense uptake in regions concordant with both tumors. The possibility of atypical AIP was a concern, but malignant tumor could not be clinically or radiologically excluded. Endoscopic ultrasonographic fine-needle aspiration biopsy was performed, but no malignant cells were detected. The patient underwent subsequent distal pancreatectomy. Histological evaluation of the tumors showed the presence of many IgG4-positive plasma cells without any evidence of malignancy.

Recombinant human growth hormone replacement in a Japanese man with a novel PROP1 gene mutation (R112X).

Congenital combined pituitary hormone deficiency (CPHD) is associated with deficiencies of anterior pituitary hormones. PROP1 gene mutations are often responsible for CPHD, but few such cases have been reported in Japan. This study describes a 37-year-old Japanese man with CPHD, treated with hydrocortisone, testosterone, and L-thyroxine, who was evaluated for adult growth hormone deficiency (GHD). Gene analysis revealed a previously unknown PROP1 mutation (R112X). After 10 months of recombinant human growth hormone (rhGH) administration, cortisol and urinary free cortisol levels were significantly lower than before therapy. This case underscores the importance of reassessing hypothalamic-pituitary-adrenal axis function in GHD patients, especially those with a PROP1 mutation, during rhGH therapy.

A decrease in the dose of pegvisomant was needed for the treatment of acromegaly after adrenalectomy in a patient with coexisting preclinical Cushing's syndrome.

We herein describe the case of a 47-year-old woman with pre-clinical Cushing's syndrome caused by a left adrenal adenoma, which was diagnosed 6 years after trans-sphenoidal selective removal of a pituitary adenoma for acromegaly at age 35. The patient was started on bromocriptine and then somatostatin analogues after the surgery; however, since her serum insulin-like growth factor-1 (IGF-1) values remained above the age-adjusted normal range, the treatment for acromegaly was switched from somatostatin analogues to pegvisomant (10 mg daily), before a left laparoscopic adrenalectomy. After the subsequent adrenalectomy, the dose of pegvisomant could be reduced gradually to once every 4 days without any increase in the serum IGF-1 values. This is the first report describing the need for a different dose of pegvisomant for the treatment of acromegaly before and after adrenalectomy for pre-clinical Cushing's syndrome.

A case of fulminant type 1 diabetes mellitus accompanied by myocarditis.

This report presents the case of a 47-year-old female patient with fulminant type 1 diabetes mellitus and myocarditis. Following a high fever, nausea, vomiting and diarrhea, diabetic ketoacidosis occurred and she was transferred to the hospital. The plasma glucose level was 63.6 mmol/L and HbA1c was 7.0%. C-peptide was undetectable in her plasma. Blood gas analysis showed a pH of 6.99. Antibodies to glutamic acid decarboxylase nor insulinoma associated antigen-2 were not detected. She was diagnosed to have fulminant type 1 diabetes mellitus. Her electrocardiogram showed diffuse ST-segment elevations on the second day of admission, along with a positive troponin test. However coronary angiography revealed neither occlusion nor stenosis of the cardiac arteries. An endomyocardial biopsy revealed hypertrophic cardiomyocytes with a disarrangement of myofibers and the focal accumulation of mononuclear cells in the stroma, thus suggesting myocarditis or mild myocarditic change. Viruses are an important cause of myocarditis and the preceding flu-like symptoms indicate the association of viral infection with myocarditis in this case. The mechanisms by which fulminant type 1 diabetes mellitus occurs is still uncertain, but the presence of islet injury accompanied by myocardial inflammation in the current case suggested that a viral infection accounted for the onset of this type of diabetes.

[A case of congenital esophageal stenosis that remained untreated until adulthood and was improved by endoscopic balloon dilatation].

A 20-year-old man had suffered from dysphagia since primary school. Upper gastrointestinal and endoscopy examinations revealed severe circumferential stenosis of the upper intra-thoracic esophagus. Secondary stenosis due to factors such as inflammation did not appear present, so congenital esophageal stenosis (CES) was diagnosed. Dysphagia improved after two endoscopic balloon dilatations. Almost all cases of CES are treated in baby-hood, and individuals who remain untreated until adulthood are rare. Check ups and diagnoses should be made taking CES into consideration, even in adults.

[A case of hepatocellular carcinoma with portal vein thrombus(Vp3)and lung metastases(stage IVB),which responded completely to treatment with Tegafur/Uracil].

A 65-year-old woman who had diffuse hepatocellular carcinoma(HCC)with tumor thrombus of right portalvein(Vp3) and lung metastases(Stage IVB)was treated by single-agent therapy with tegafur/uracil(UFT). As a result, primary and metastatic tumors were not recognized by diagnostic imaging, with a noted decrease of AFP, AFP-L3 and PIVKA-II. Generally, oral chemotherapy for HCC is not recommended because of the low response rate. However, there have been some reports including the present case which have showed a marked response with UFT. We thus conclude that UFT can be an option with low risk of crucial adverse effects in the treatment of selected HCC patients.

Gas-containing pericardial abscess in a type 2 diabetic patient.

A 63-year-old male with type 2 diabetes mellitus was admitted to our hospital with fever and chest pain. An echocardiogram, chest CT and MRI showed the gas-containing pericardial abscess located posteriol to the right atrium. He was initially treated by thoracoscopic pericardial fenestration to set a drainage tube in the pericardial abscess. However, the surgical treatment was discontinued because of a large amount of bleeding from the abscess wall. The patient was then treated by continued administration of antibiotics and gamma-globulin. The inflammatory reactions improved and shrinkage of the abscess was confirmed.

Case of adrenal incidentaloma in which autonomous cortisol production became clear during a very short term.

A 57-year-old woman was admitted to the hospital for the further evaluation of a left adrenal incidentaloma measuring 45 mm x 33 mm. She had no signs of the clinical manifestation of hypercortisolism. An endocrine evaluation revealed that her ACTH level was normal and cortisol values were almost normal pattern excluding the value at 9 PM slightly rising, however, the cortisol was not completely suppressed by the overnight administration of 1 mg dexamethasone. These findings indicated that subtle abnormalities of the hypothalamo-pituitary-adrenal axis were present in this case. After 3 months, surprisingly, the ACTH was suppressed to low levels. Further hormonal investigations revealed that the cortisol level was normal but had an abnormal diurnal rhythm and was not suppressed completely by a 1 mg or an 8 mg overnight dexamethasone dose. Adrenal scintigraphy revealed positive uptake in the left adrenal tumor with no uptake in the right adrenal gland. The patient underwent a left laparoscopic adrenalectomy. Microscopically, the tumor displayed histopathological features in common with ACTH-independent macronodular adrenocortical hyperplasia, including clear cell predominance, a pattern of small compact nests in clear cell areas, and a cord-like arrangement of small compact cells. An in situ hybridization study demonstrated the hybridization signals for P-450scc, 3beta-HSD, P-450c21, P-45011beta, and P-45017a which were observed in the clear cells as well as compact cells, the compact cells being more intensely stained. This case indicates the ability of autonomous cortisol production to become clear during a very short term and a more detailed and careful short-time follow-up should be recommended in patients with adrenal incidentalomas.

Autopsy of a patient with Cushing's Syndrome who was revealed to have pulmonary tumorlets producing ectopic ACTH.

The patient, a 78-year-old female with a 10-year history of type 2 diabetes mellitus, was admitted to our department for evaluation of leg edema and general fatigue. Biochemical investigations revealed hypokalemia and elevated serum cortisol and plasma ACTH levels, with a loss of diurnal rhythm and failure of suppression at high doses (8 mg) of dexamethasone. No pituitary tumor or parasellar tumor was detected by contrast-enhanced computed tomography (CT) or magnetic resonance image scan of the pituitary. High resolution CT of the lung and bronchoscopic examination revealed no abnormalities. Abdominal and pelvic CT indicated bilateral, slightly diffuse, adrenal gland hyperplasia only. These findings led to a diagnosis of ACTH-dependent hypercortisolism from an undefined source. Ten days after admission the patient had a fever and was diagnosed with disseminated intravascular coagulation. Despite intensive treatment about 1 month after admission the patient died from progressive multiple organ failure. At autopsy, a histological examination of the periphery of the right middle lobe of the lung revealed the presence of tumorlets. Immunohistochemical staining of the tumorlets revealed scattered cells containing ACTH and many cells containing chromogranin A that were positive for Grimelius staining. In addition, multiple microabscesses were present throughout most tissues of the body. The ectopic hormonal production observed in the present case suggests that pulmonary tumorlets should thus be considered in the differential diagnosis of Cushing's syndrome, and medical treatment to inhibit steroidogenesis should be started immediately to reduce the risk of complications from hypercortisolism.

Short term intensive insulin therapy improves insulin secretion significantly in type 2 diabetic patients.

To investigate the effects of short-term (1 week) intensive insulin therapy, on glycemic control, insulin secretion, and insulin sensitivity in type 2 diabetic patients, an open prospective study was conducted in sixteen type 2 diabetic patients receiving diet therapy alone or treatment with oral hypoglycemic agents. Of the study subjects, 8 patients were treated with insulin, the remaining 8 patients served as the control group. The metabolic parameters were evaluated once before treatment and once during one of the following treatments : glycemic control as measured by 1,5-anhydro-D-glucitol (1,5-AG) and area under curve of glucose (AUCglucose), insulin secretion as measured by area under curve of daily serum insulin (AUCinsulin), and insulin sensitivity as measured by the K index of the insulin tolerance test (K(ITT)). Post-treatment plasma glucose (AUCglucose) and 1,5-AG levels in patients who had received intensive insulin therapy were comparable to those of the control group. A statistically significant increase in AUCinsulin occurred after intensive insulin therapy for just 1 week, while no change occurred in the control group. Insulin sensitivity (K(ITT)) did not improve significantly in patients treated with insulin or patients from the control group. These results indicate that intensive insulin therapy for 1 week improves insulin secretion remarkably but has little effect on insulin sensitivity in type 2 diabetic patients. Clinically, this suggests that intensive insulin therapy for one week might be one of the initial treatments of choice for such patients.