Salivary duct carcinoma in the mandible: a case report

Salivary duct carcinoma (SDC) is a distinctive and aggressive neoplasm. The most frequent site of origin is the parotid gland, followed by the submandibular gland. SDC originating in the minor salivary glands, particularly in the ectopic glands within the mandible, is extremely rare. We describe a 62-year-old man with SDC in the mandible, who presented with a painless lump in the right submandibular region (later identified as lymph node metastasis) and ipsilateral mental nerve palsy. Histologic examination after ablative surgery revealed SDC originating in the mandible and cervical nodal metastases spreading to levels I-III. The patient remains alive 59 months after presentation as a result of postoperative full-dose irradiation and regular intensive chemotherapy using TXT, 5-FU, and CDDP. However, the patient has local recurrence and distant metastases to the lung and brain. In this report, we also discuss the specific diagnostic criteria and developmental theories of intraosseous salivary gland tumors.     

Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens

Rationale

The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.

Objectives

Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.

Methods

Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.

Results

Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition.

Conclusions

The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.     

Regorafenib in Japanese patients with solid tumors: phase I study of safety,efficacy, and pharmacokinetics

The safety, pharmacokinetics, and antitumor activity of the multikinase inhibitor regorafenib in Japanese patients was assessed in this multicenter, single-arm, phase I trial. Fifteen patients with treatment-refractory advanced solid tumors received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, unacceptable toxicity, or investigator or patient decision to stop. The median duration of treatment was 2.1 months (range, 0.9–20.1 months). At data cutoff, one patient was still receiving regorafenib in cycle 21. Reasons for treatment discontinuation were disease progression (n?=?12) and adverse events (liver enzyme elevation n?=?1; anemia n?=?1). Adverse events necessitated dose reduction in six patients, interruption of daily treatment in seven patients, and cycle delay in four patients. All patients experienced at least one drug-related adverse event, particularly gastrointestinal (87 %), dermatologic (73 %), or hematologic (67 %) events. There was no significant change in time to maximum concentration or terminal half-life of regorafenib and its active metabolites M2 and M5 between single dosing and 21-day continuous dosing. The area under the concentration–time curve was 2.1-fold higher for regorafenib, 5.2-fold higher for M2, and 37.3-fold higher for M5, and the maximum concentration was 2.0-fold, 4.8-fold, and 36.0-fold higher, respectively, after continuous dosing than after single dosing. One patient had a partial response (duration 10.5 months) and seven patients had stable disease. This study indicates that regorafenib 160 mg orally once daily (21 days on/7 days off treatment) can be given to Japanese patients who have solid tumors, without undue toxicity.     

Blood pressure after treatment with sodium–glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease.Materials and MethodsWe assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year.ResultsBy propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg.ConclusionsIn Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.     

Association between Grit Scales and adherence to regular hospital visits among Japanese patients with type 2 diabetes: Prospective observational study

This study examined the association between Grit Scales and adherence to a schedule of regular hospital visits among Japanese type 2 diabetes patients. Patients with type 2 diabetes who visited the outpatient clinic as new patients comprised the study’s participants. Self-administered Short Grit Scale data were obtained from 122 patients at the first consultation and were then observed for 1 year. As the results, 21 participants failed to attend the hospital. In a logistic regression analysis, the Grit Scale as a continuous variable was positively associated with adherence to regular clinical visits. Its odds ratio and 95% confidential interval was 9.68 and 2.87–32.65 (P = 0.0003). In conclusion, it is likely that the Grit Scale is closely associated with adherence to regular hospital visits among Japanese type 2 diabetes patients.