Age, Symptomatic Metastatic Disease, and Malignant Pleural Effusion as Predictors of Poor Prognosis in Patients with Differentiated Thyroid Carcinoma Treated with Lenvatinib.

Background: Lenvatinib is one of the few therapeutic options available for radioiodine-refractory thyroid cancer. However, the factors that determine the therapeutic outcomes remain unknown.Methods: Patients with thyroid carcinoma treated with lenvatinib who had been dead or who had survived for longer than a halfyearwere retrospectively compared. We evaluated the clinical parameters when lenvatinib was started, and also studied the tumor volume reduction ratio, the duration until re-growth of the largest metastatic lesion, the thyroglobulin (Tg) reduction rate,and the duration until re-elevation of Tg after lenvatinib between survivors and dead patients.Results: We identified 16 patients, with an average age of 73.1±7.6 yrs and a male-to-female ratio of 5 to 11, who had advanced differentiated thyroid cancer that was treated with lenvatinib. Nine patients had died after 8.9±6.1 months, whereas 7 survived for 13.0±2.0 months after starting lenvatinib. The patients who died were older than the survivors (76.7±6.5 vs. 68.6±6.6 yrs, p=0.03).Malignant pleural effusion (p=0.017) and symptomatic metastatic disease (SMD) (p=0.039) were associated with death in a Kaplan-Meier survival analysis. Age (p=0.012, HR 1.150, CI 1.030-1.320) and SMD (p=0.014, HR 8.069, CI 1.503-61.34) wereassociated with poor outcome in a multivariate Cox proportional hazard model. The duration until the re-elevation of Tg waslonger in survivors than in patients who died (6.43±4.55 vs. 2.17±1.39 months, p=0.025).Conclusions: We identified multiple factors, including SMD, that were related to poor outcomes after lenvatinib treatment. This study suggests that lenvatinib might be started before patients develop SMD

Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3 variant in the Japanese population

Objective: Type 1 diabetes (T1D) iscommonlyassociated withautoimmunethyroid disease (AITD),and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population. Design/Patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present. Results: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405- DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects. Conclusions: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms

Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine

AIM : Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa. METHODS : We compared the PGE2 and LTB4 levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group ; n=5), and the group treated for 8 weeks with an H2 blocker, ranitidine (H2 blocker group ; n=6), as well as in nonulcer subjects (control group ; n=5). RESULTS : The mucosal levels of PGE2 and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB4 level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE2 and decreased LTB4 levels in comparison to the H2 blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H2 blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H2 blocker group during the ulcer-healing stage. CONCLUSION : These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE2 production and reducing the LTB4 production

A case of compressive optic neuropathy putatively caused by IgG4-related idiopathic orbital inflammation.

We report the case of a 58-year-old male presenting with an impairment of the left-sided visual acuity caused by compressiveoptic neuropathy, and marked bilateral proptosis. Blood test showed markedly elevated IgG4 (1830 mg/dl) and positiveTSH receptor-stimulating antibodies (200%), but the thyroid function test were normal. Orbital MRI revealed abnormal soft tissueproliferation around the optic nerve and fusiform enlargement of the extraocular muscles. Systemic CT analysis detectedmultiple lymph node swelling, pseudotumor in the lung, retroperitoneal fibrosis, and kidney lesions. We considered that the eyemanifestation was most likely caused by IgG4-related idiopathic orbital inflammation. Systemic administration of a moderatedose of prednisolone dramatically improved the compression of the optic nerve, as shown by the improvement of the visualacuity and the MRI findings. The clinical course made thyroid-associated ophthalmopathy unlikely. In conclusion, an overallconsideration of the clinical picture and extensive work-up of any possible differential diagnosis including measurement of theserum levels of IgG4 was highly useful in making the diagnosis of the patient

An incident involving blood sucking by a tick in a suburb in Japan

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan

A patient with adult extrahepatic portal obstruction, of which distinction from intrahepatic cholangiocarcinoma was difficult

A 51-year-old Japanese male with chief complaints of slightly high fever and epigastralgia was hospitalized at our facility. The inflammatory response was enhanced, and liver dysfunction was observed. Abdominal ultrasonography demonstrated a hyperechoic lesion occupying the left portal vein, and abdominal plain CT indicated a low density of the lesion with a clear boundary, measuring about 3 cm× 2 cm, between the porta hepatis and segment IV of the liver. Contrast CT showed no enhancement in the arterial and portal phases, but a reduction in the density inside the tumor in the equilibration phase was noted. MRI showed hypointensity by T1-weighted imaging and hyperintensity by T2-weighted imaging. Angiography demonstrated an obstruction of the left portal vein and superior mesenteric vein, and endoscopic retrograde cholangiography revealed a constriction in the left intrahepatic bile duct. Since the possibility of intrahepatic cholangiocarcinoma could not be excluded, extended left hepatectomy combined with caudate lobectomy was performed. The tumor, measuring 31 mm× 21 mm×20 mm, was pathohistologically diagnosed as an extrahepatic portal obstruction. Extrahepatic portal obstruction is an important disease that is sometimes difficult to rule out oncologic origin

Graves\u27 disease complicated by ventricular fibrillation in three men who were smokers.

Thyrotoxicosis is known to be associated with sinus tachycardia and supraventricular tachyarrhythmias, but rarely with ventricular fibrillation (Vf), which has only occurred in some patients with hypokalemic periodic paralysis or ischemic heart disease. PATIENT FINDINGS: We present three men who were transferred to our hospital with Graves\u27 disease who developed idiopathic Vf. None of them had hypokalemic periodic paralysis or ischemic heart disease but all were smokers. None of other patients with thyrotoxicosis (587 females and 155 males) who were seen at our hospital, in the period during which the three men were seen, had idiopathic Vf. In our three men with thyrotoxicosis and idiopathic Vf, there was no identifiable underlying heart disease. One of the three patients died of hypoxic encephalopathy. The other two men did not have recurrent Vf after their thyroid function normalized

A patient with octopus pot-shaped cardial cancer that metastasized to multiple organs

A 71-year-old male was admitted for abdominal fullness. The condition rapidly deteriorated in a short period (3weeks), and the patient died. Autopsy revealed a protruding lesion measuring about 3 cm with erosion measuring 5mmin diameter immediately below the esophago-gastric conjugation site, suggesting primary cardial undifferentiated adenocarcinoma. In the primary focus, changes on the mucosal surface were almost normal. However, below the mucosa, infiltration of cancer cells was observed in an approximately 3 cm area along the gastric wall. Simultaneously, the site of infiltration was markedly increased in deep areas. Extra serous infiltration was observed. The morphology was special, and resembled an octopus pot, a trap used to catch octopuses in Japan, with a narrow top and a broad base. In our patient, metastatic lesions were detected in multiple organs, including the stomach

Recurrent giant longitudinal duodenal ulcer with massive hemorrhage in a Helicobacter pylori-negative patient

A 67-year-old man, in whom a linear ulcer running from the duodenal bulb to the descending part had been noted 3 years previously, was admitted to our hospital because of abdominal pain and melena. Duodenoscopy revealed a bleeding giant longitudinal ulcer, which was more extensive than before. Tests for Helicobacter pylori (Hp) were negative. The ulcer was cured by endoscopic hemostasis and repeated blood transfusions. Attention must be paid to Hp-negative post-bulbar duodenal ulcers because of the frequent complications including hemorrhage

Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding basal-bolus insulin: Association between the responses of β- and α-cells to GLP-1 stimulation and the glycaemic control at 6?months after switching therapy

Aims: To evaluate the glycaemic control of combination therapy with basal insulin and liraglutide, and to explore the factors predictive of efficacy in patients with type 2 diabetes when switched from longstanding basal-bolus insulin therapy. Methods: We studied 41 patients who switched from basal-bolus insulin therapy of more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic control was evaluated at 6 months after switching therapy and used to subdivide the patients into good-responders (HbA1c <7.0% or 1.0% decrease) and poor-responders (the rest of participants). To evaluate the glucose-dependent insulin/glucagon responses without/with liraglutide, a 75-g oral glucose tolerance test (OGTT) was performed twice, before (1st-OGTT) and 2-days after (2nd-OGTT) liraglutide administration. Results: Twenty-eight patients (68.3%) were identified as good-responders. No differences were found in baseline characteristics including insulin/glucagon responses during 1st-OGTT between the groups. 2nd-OGTT revealed that paradoxical hyperglucagonemia were significantly improved in both groups, but significant increases in insulin secretory response were observed only in good-responders. Logistic regression analyses revealed that the improvement of the insulin-response during 2nd-OGTT compared to that during 1st-OGTT is associated with the good-responder. Conclusions: Enhancement of glucose-dependent insulin-response under liraglutide administration is a potential predictor of long-term glycaemic control after switching the therapies