Double pituitary neuroendocrine tumors in a patient with normal growth hormone level acromegaly: A case report and review of the literature.

Background: Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion caused by a pituitary neuroendocrine tumor (PitNET). However, some acromegaly patients show normal GH levels, and they can be a pitfall in clinical diagnosis. Moreover, rarely, synchronous true double or multiple PitNETs are encountered. Moreover, these PitNETs increase the risk of a left lesion during surgical exploration. Case Description: The patient, who was a 73-year-old female, was referred to our hospital with a chief complaint of headache. Assessment of basal anterior pituitary function revealed a slightly high level of insulin-like growth factor-1 (IGF-1) (standard deviation, 2.4), and her physical findings exhibited mild acromegalic features. The endocrine evaluation confirmed acromegaly and magnetic resonance imaging (MRI) showed a macro PitNET with suprasellar extension. Endoscopic endonasal surgery (EES) was performed to remove the macro PitNET. Although postoperative MRI showed complete removal of the macro PitNET, endocrinological testing indicated no improvement in GH or IGF-1 excess. Pathological examination of the surgical specimen revealed a gonadotropic PitNET. Therefore, we repeated the MRI scan and found a micro PitNET in the thin left normal pituitary gland. A second EES was successfully performed to remove the micro PitNET completely, and both endocrinological and pathological examinations confirmed that the disease was cured. Conclusion: Diagnosing acromegaly with low GH levels requires close monitoring. Double PitNETs are relatively rare and can cause incomplete remission of functional PitNETs.

A Case of Dermoid Cyst Arising in the Temporal Lobe.

Intracranial dermoid cysts are rare congenital lesions that result from abnormal sequestration of ectodermal cells during neural tube formation. These tumors are especially rare in lateral areas such as in the temporal lobe. In this study, we report a case of dermoid cyst located in the right temporal lobe. A 50-year-old man was referred for further treatment of a tumor. CT revealed a low-density mass lesion in the right temporal lobe, with calcification. MRI showed the lesion with high signal intensity on diffusion-weighted imaging, high-low mixed signal intensity on T1-weighted imaging, and iso-high signal mixed intensity on T2-weighted imaging; the capsule was enhanced with gadolinium. Differential diagnosis included dermoid cyst, epidermoid cyst, teratoma, and neurenteric cyst. We decided to perform surgery for the improvement of his symptom, histopathological diagnosis, and radical cure. A right temporal craniotomy was performed, and the tumor was found adherent to the surrounding brain tissue. The tumor was completely removed under subpial dissection. Hair was confirmed in the tumor content. On histopathology, the cyst wall was lined with stratified squamous epithelium, sebaceous glands, small vessel aggregates, and inflammatory infiltrate. Keratinized material and hair were found in the lumen. The patient was discharged 7 days after surgery with no new neurologic deficits. This case was unusual in terms of the effect of gadolinium enhancement on MRI, and the presence of adipose tissue and calcification were useful for diagnosis. It is vital to consider prevention of chemical meningitis due to intrathecal dissemination of the tumor content intraoperatively.

A Case of Nervus Intermedius Neuralgia.

BACKGROUND: Nervus intermedius neuralgia is an extremely rare craniofacial neuralgia characterized by paroxysmal episodes of pain located deep in the ear, typically triggered by sensory or mechanical stimuli at the wall of the auditory canal without underlying pathology. Pain is sometimes associated with disorders of lacrimation, salivation, and taste. CASE DESCRIPTION: We present a case of a surgically treated 68-year-old man with left paroxysmal deep ear pain for 20 years before presentation. Preoperative 3-dimensional magnetic resonance cisternography/magnetic resonance angiography (3D-MRC/MRA) fusion imaging showed severe compression of the facial nerve by the anterior inferior cerebellar artery in the cisternal portion with associated nerve deformity. We suspected nervus intermedius neuralgia and decided to perform microvascular decompression of the facial nerve. Transposition of the artery led to sufficient decompression of the nerve. The pain disappeared immediately after surgery. CONCLUSIONS: It is important to keep in mind the possibility of nervus intermedius neuralgia in patients who present with intermittent episodes of pain located deep in the ear. Furthermore, 3D-MRC/MRA fusion imaging is useful for decision-making in surgery. Microvascular decompression was highly effective in our case. Based on radiological findings, microvascular decompression should be considered a viable treatment option.

Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema After Carotid Endarterectomy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) and neurogenic pulmonary edema (NPE) are rare complications of an acute ischemic stroke. In particular, TCM and NPE following carotid endarterectomy (CEA) are extremely rare. In general, TCM- and NPE-associated ischemic strokes are caused by excess catecholamine release after sympathetic nervous stimulation following stroke onset, but the mechanism triggering this stimulation is still unknown. CASE DESCRIPTION: An 88-year-old man underwent left CEA for symptomatic carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial, 65%). After the surgery, his respiratory condition rapidly worsened, and chest radiography revealed an infiltrative shadow on both lung fields. Transthoracic echocardiography revealed left ventricular dysfunction, suggesting TCM. Postoperative magnetic resonance imaging revealed a small infarction in the left anterior insular cortex. Eventually, his respiratory and cardiac functions gradually improved. He was finally discharged on his own from the hospital on postoperative day 9. CONCLUSIONS: We described a very rare case of TCM and NPE following CEA. The mechanisms of TCM and NPE involve excess catecholamine release after sympathetic nervous stimulation. Our findings suggest that surgery-associated transient ischemia and reperfusion injury to the left insular cortex stimulate sympathetic nerves.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma.

BACKGROUND: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model. METHODS: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy. RESULTS: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. l-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers. CONCLUSION: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent l-carnitine is a good candidate to control oxidative stress conditions.

Lemierre Syndrome Associated with Ipsilateral Recurrent Laryngeal Nerve Palsy: A Case Report and Review.

Lemierre syndrome (LS) is a rare life-threatening disease that is often caused by an acute oropharyngeal infection with a secondary thrombophlebitis of the internal jugular vein. LS rarely manifests as cranial nerve palsy. To the best of our knowledge, this is the second case report of LS associated with recurrent laryngeal nerve palsy. A 66-year-old female presented to a dental clinic with gingivitis and sore throat. Due to moderate periodontitis, her left first upper molar was extracted. A few days later, she subsequently developed a coarse voice and occipital headaches, and was referred to an otolaryngologist. She was diagnosed with left recurrent laryngeal nerve palsy and subsequent left-sided otitis media, and was referred to us for persistent headaches. She intermittently presented with high-grade fever and complained of salty taste disturbance. Her head magnetic resonance imaging (MRI) revealed left mastoiditis, thrombosis in the left transverse and sigmoid sinus, and left internal jugular vein. Her laboratory tests revealed an elevated white blood cell count, levels of C-reactive protein, and D-dimer. No endogenous coagulopathy was confirmed. Although, blood and cerebrospinal fluid culture grew no microorganisms, respectively, the empirically determined antibiotic therapy was initiated. In a week, the patient defervesced and had no headaches despite persistent thrombosis. Early diagnosis and an immediate antibiotic treatment are crucial for LS patients. Anticoagulation therapy was not needed for our patient and is still controversial for LS.

Recurrence after radiotherapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma with trisomy 18.

A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.

L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% α-tocopherol (α-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial ß-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial ß-oxidation and redox system.

Characteristics of serious complicated gastroduodenal ulcers in Japan.

BACKGROUND/AIMS: Even in Japan where the incidence of H. pylori infection is high, patients with gastroduodenal ulcers caused by NSAIDs are on the increase. A prospective study was conducted to elucidate the characteristics of gastroduodenal ulcers complicated with ulcerous hemorrhage and perforation among Japanese. METHODOLOGY: The subjects were 305 consecutive cases with hemorrhaging ulcers and 76 consecutive cases with perforated ulcers basis at Kagawa Prefectural Central Hospital between January 2000 and December 2008. These subjects were divided into 3 groups (lowdose aspirin, non-aspirin NSAIDs and non-NSAIDs) and were further stratified by the presence of an H. pylori infection. RESULTS: The 76 perforating ulcers were composed of 54 non-NSAIDs ulcers and 22 NSAIDs-related ulcers. The 305 hemorrhaging ulcers were composed of 156 non-NSAIDs ulcers, 94 non-aspirin NSAIDs ulcers and 55 on low-dose aspirin. The mortality for the non-aspirin NSAIDs group (12.8%, 12/94) and for the low-dose aspirin group (10.9%, 6/55) was significantly higher (p<0.01 and p<0.05, respectively) than the corresponding figure (2.6%, 4/156) for the non-NSAIDs group. The causes of death were exacerbation of or complications from the background diseases (Charlson Co-morbidity Index 3≤) (Odds ratios (OR) 6.01, 95% CI (1.98-18.89)). CONCLUSIONS: Approximately 50% of the gastroduodenal ulcers with complications found in Japanese are NSAIDs-related and may take a fatal turn. It is necessary to take measures to prevent the complicated ulcers corresponding to risk factors such as the severity of background diseases.

[A case of hemolytic uremic syndrome after adjuvant chemotherapy with gemcitabine in a patient with pancreatic cancer].

A 63-year-old man with Stage IVa pancreas tail cancer was admitted for a distal pancreatectomy and splenectomy; adjuvant chemotherapy with gemcitabine was also administered. The chemotherapy was terminated after 16 courses due to hemolytic anemia, thrombocytopenia and renal dysfunction. Plasma exchange was performed; however the patient's renal function was diminished, requiring chronic hemodialysis. Physicians should be cautious of hemolytic uremic syndrome as a possible adverse reaction to gemcitabine and be aware that tests are needed for its early detection.

Basal protrusion of ulcers induced by endoscopic submucosal dissection (ESD) during treatment with proton pump inhibitors, and the suppressive effects of polaprezinc.

BACKGROUND/AIMS: When a peptic ulcer is treated with proton pump inhibitors (PPI), protrusion of the ulcer base is sometimes noted during ulcer healing. To clarify the incidence of ulcer base protrusion in ulcers induced by endoscopic submucosal dissection (ESD), and whether the addition of polaprezinc, a cytoprotective agent used for treatment of gastric ulcer, to the PPI regimen helps to suppress it. METHODOLOGY: One hundred sixty-three patients on which ESD was performed were randomly allocated to either two groups: one treated with lansoprazole (30mg/day) and the other with lansoprazole (30mg/day) plus polaprezinc (150mg/day) for the treatment of ESD-induced ulcer. The condition of the ESD-induced ulcer was blindly assessed two months after ESD by two physicians. RESULTS: Lansoprazole plus polaprezinc group showed significantly better ulcer healing (p < 0.0001) and protrusion of the ulcer base was recognized in only 1.3% (1/77), an incidence significantly lower than that in lansoprazole group (20.7%, 16/77, p = 0.0001). Polaprezinc was the only significant factor (p = 0.0001) differentiating patients who had ulcer base protrusion (n = 17) from those who did not (n = 137). CONCLUSIONS: Polaprezinc prevents protrusion of the ulcer base during the healing of ESD-induced ulcer with PPI.

[Autoregulation of dynamic cerebral blood flow during hypotensive anesthesia with prostaglandin E1 or nitroglycerin].

BACKGROUND: Autoregulation of dynamic cerebral blood flow during hypotensive anesthesia is unclear. We examined the effects of hypotensive anesthesia with prostaglandin E1 (PGE1) or nitroglycerin (NTG) on autoregulation of the dynamic cerebral blood flow. METHODS: Beat-by-beat mean arterial pressure (MAP) and blood flow velocity in the middle cerebral artery were measured before and during hypotensive anesthesia. The relationship between changes in MAP and cerebral blood flow velocity was evaluated by using the method of transfer function analysis. We calculated transfer function gain and coherence by cross-spectrum from autospectra of MAP and blood flow velocity in the low (0.07-0.2 Hz) and high (0.2-0.3 Hz) frequency ranges. RESULTS: The gain in the both frequency ranges was unchanged during hypotensive anesthesia with PGE1. During hypotensive anesthesia with NTG, the gain in the high frequency range was unchanged, either. However, the gain in the low frequency range increased during hypotensive anesthesia with NTG. The value was significantly higher than in hypotensive anesthesia with PGE1. CONCLUSIONS: These results suggest that hypotensive anesthesia with PGE1 maintains autoregulation of the dynamic cerebral blood flow, but NTG impairs the autoregulation in the low frequency range.

[Dynamic cerebral blood flow autoregulation during sevoflurane anesthesia and TIVA].

BACKGROUND: Dynamic cerebral blood flow autoregulation during sevoflurane anesthesia and total intravenous anesthesia (TIVA) is unclear. We examined the cerebral circulation autoregulation during anesthesia by sevoflurane or TIVA. METHODS: We measured mean blood pressure (MBP) and blood flow velocity of the middle cerebral artery by a transcranial Doppler ultrasonography before and during anesthesia using sevoflurane (volatile induction and maintenance of anesthesia (VIMA) group) and using propofol and fentanyl (TIVA group), and the relationship between changes in MBP and cerebral blood flow velocity was evaluated using the method of transfer function analysis. We calculated transfer gain and coherence by cross-spectrum from autospectra of MBP and cerebral blood flow velocity. RESULTS: Transfer gain during anesthesia by TIVA in the low frequency range and high frequency range was near 1 cm.sec-1.mmHg-1. It was about equal to the value of transfer gain before anesthesia. But transfer gain during anesthesia by VIMA was above 2 cm.sec-1.mmHg-1. CONCLUSION: These results suggest that TIVA by propofol and fentanyl maintains the dynamic autoregulation of cerebral blood flow, but sevoflurane impairs the autoregulation.