Although the incidence of gastric cancer has decreased because of the lower rate of Helicobacter pylori infection, it still accounts for a large number of deaths in Japan. Gastric cancer is mainly treated by resection, and the rate of radical resection is high in Japan because approximately 50% of cases are diagnosed at an early stage. Treatment advances have increased the number of endoscopic submucosal dissections, and development of laparoscopic surgery and robot-assisted surgery as minimally invasive approaches has yielded results similar to those of conventional surgeries, at least in the short term. Cases for which resection is contraindicated are treated with chemotherapy if performance status can be maintained. Although anticancer drugs are continuously under development, treatment outcomes remain unsatisfactory. As Japan becomes a super-aging society, the number of refractory cases is projected to increase. Therefore, evidence of any benefit for minimally invasive surgery and function-preserving surgery needs to be reported quickly. In this paper, we discuss gastric cancer treatment modalities recommended in the fifth edition of the gastric cancer treatment guidelines and describe recent research findings.

Chronic hepatitis C virus (HCV) infection can progress to liver cirrhosis and hepatocellular carcinoma. Interferon-based treatment was previously the only antiviral therapy for chronic hepatitis C infection; however, development of interferon-free, direct-acting antivirals, in 2014, markedly improved treatment efficacy and safety. Treatment indications were expanded to include elderly adults, patients with advanced liver fibrosis, and patients with chronic hepatitis C infection complicated by chronic kidney disease, for whom antiviral therapy had been difficult or contraindicated. The median age of patients with chronic HCV infection in Japan is 70 years, older than in other countries. Because diminished renal function is common in elderly adults, a safe and effective treatment for chronic hepatitis C complicated by chronic kidney disease has been expected in Japan. In addition, the HCV antibody-positive rate is higher in hemodialysis patients than in non-hemodialysis patients in Japan. Numerous studies have reported that direct-acting antivirals are safe and effective for hepatitis C patients on hemodialysis. This review summarizes treatments available in Japanese clinical practice for patients with chronic HCV infection complicated by chronic kidney disease, including hemodialysis patients.

Atopic dermatitis (AD) is a chronic eczematous disease characterized by T helper 2 (Th2) -shifted allergic immunity, skin barrier impairment, and pruritus. Oral intake of certain nutrients might help regulate AD. Serum 25-hydroxyvitamin D levels are often low in patients with AD, and oral vitamin D supplementation improves AD. Vitamin D increases regulatory T (Treg) cells, which promote tolerance to allergens and prevent allergic inflammation by inducing expression of filaggrin and cathelicidin in keratinocytes. Vitamin A strengthens Treg cells by inducing expression of forkhead box P3 and inhibits mediator release from mast cells and eosinophils. Serum levels of γ-linolenic acid and its metabolite, dihomo-γ-linolenic acid, are low in patients with AD, and oral γ-linolenic acid improves AD through anti-inflammatory prostaglandin D₁ and E₁ derived from dihomo-γ-linolenic acid. Eicosapentaenoic acid and docosahexaenoic acid ameliorate AD by suppressing production of leukotriene B₄, increasing ceramides in the stratum corneum, and through their metabolites, resolvin E1 and D1, which resolve inflammation. The probiotics Lactobacillus and Bifidobacteria improve the intestinal permeability barrier and induce Treg cells. Zinc levels in serum, hair, and erythrocytes are diminished in patients with AD. Zinc induces forkhead box P3 expression and increases Treg cells, and zinc-finger protein A20 suppresses nuclear factor-κB-dependent expression of inflammatory cytokines and cell-adhesion molecules. Oral supplementation of the above nutrients might have therapeutic or preventive roles in AD.

Background: We evaluated children with hypertension and compared those with essential and secondary (including renal and non-renal) hypertension. Methods: This retrospective study analyzed data from hypertensive children (age, 0-18 years) referred for treatment between January 2008 and December 2015. Demographic factors, causative factors, and medical treatments were evaluated. Treatment failure was defined as a systolic or diastolic blood pressure ≥95th percentile for age, gender, and height on three separate occasions, despite treatment. All patients not meeting the failure criteria were considered to have controlled hypertension. The control rate was defined as the proportion of patients with controlled blood pressure. Results: Among 172 consecutive patients, 28% had essential hypertension and 72% had secondary hypertension. As compared with children with secondary hypertension, those with essential hypertension had a higher frequency of family history of hypertension (P<0.001), a higher body mass index (BMI) (P=0.001), lower frequency of proteinuria (P=0.003), lower uric acid (P=0.04), and lower triglyceride (P=0.048). The medications used in the controlled group were similar to those used in the uncontrolled group. Angiotensin-converting enzyme inhibitors (ACEIs) were only used in nephrogenic patients, and a higher rate of ACEI use seemed to increase control rates. Control rates did not significantly differ by age, number of drugs, or cause of hypertension. Conclusions: As compared with children with secondary hypertension, those with essential hypertension were more likely to have a family history of hypertension and had a higher BMI, lower frequency of proteinuria, and lower uric acid and triglyceride concentrations. Treatment guidelines for essential and secondary hypertension should be established for children of all ages.

Background: Oxidative stress is thought to be closely related to epileptogenesis. We have previously reported that nitric oxide (NO) levels are higher in epilepsy-prone EL mice between the ages of 3 and 8 weeks than in control mice. However, NO is divided into two fractions, nitrite (NO₂) and nitrate (NO₃), which appear to play different roles in epileptogenesis. Methods: NO₂ and NO₃ levels were measured, in EL mice and the control mice, in the parietal cortex, which is thought to be the primary epileptogenetic center in EL mice, and measured in the hippocampus, which is thought to be the secondary center. Results: NO₃ levels in the hippocampus and parietal cortex of the immature EL mice (3 to 8 weeks of age) were significantly higher than those in the control mice; NO₂ levels were significantly higher in the EL mice throughout the study period. The NO₃ levels were significantly higher than the NO₂ levels in the immature EL mice, but after the onset of ictogenesis at 10 weeks of age, the relative levels of the two fractions reversed. Conclusion: The reversal of the NO fraction distribution at the onset of seizures that we observed may be related to the developmental process of seizure susceptibility in the neural network of EL mice.

Background: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. Methods: We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. Results: The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001). Conclusions: Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Background: The purpose of this study was to examine changes in the ocular surface before and after phacoemulsification with small incisions and to examine the changes in tear osmolarity. Methods: This was a prospective, observational study involving 55 eyes of 39 patients (19 male, 20 female patients; average age 72.0±7.3 years) who had cataract surgery at a Nippon Medical School Hospital between December 2013 and June 2018. Compromised tear dynamics were determined by the Schirmer test or the tear break-up time (BUT). An abnormal ocular surface was identified by positive vital staining with fluorescein or lissamine green. Moreover, tear osmolarity (Tosm) and corneal sensitivity were measured. All assessments were done preoperatively and 1 and 4 weeks (P1W and P4W) after the surgery. Results: None of the operations had any complications. Operating time was 17.8±9.3 minutes. BUT was significantly decreased at P1W, and it recovered at P4W. The Schirmer test did not change significantly. The fluorescein staining score (FSS) increased significantly at P1W and recovered at P4W. The Lissamine green score (LSS) did not change significantly. Tear osmolarity increased significantly at P1W and did not recover at P4W. Corneal sensitivity decreased significantly at P1W and recovered at P4W. Conclusion: In the present study, there were temporary changes in dry eye-related examinations including tear osmolarity after cataract surgery. In particular, tear osmolarity increased significantly 4 weeks after surgery compared to before surgery, and it showed long-term changes, unlike other factors. After cataract surgery, tear osmolarity, BUT, and FSS increase, resulting in dry eye symptoms. Therefore, it is necessary to pay attention to discomfortable eye symptoms of patients after cataract surgery.

Background: There have been no comprehensive studies of changes in heart gene expression due to ethanol exposure. Therefore, we attempted to determine gene expression in cultured neonatal rat cardiomyocytes exposed to ethanol (0, 10, 50, 100 mM) for 24 h. Methods: The total RNA extract of beating cardiomyocytes was evaluated by DNA microarray analysis, and fold changes (FCs) in differential gene expression of ethanol-exposed cardiomyocytes were analyzed against the control using Ingenuity Pathway Analysis (IPA) software. Results: The 1,394 genes with an |FC| of ≥1.8 were uploaded to IPA. IPA predicted 23 canonical pathways working in the ethanol groups. Three canonical pathways related to ethanol degradation- "Ethanol Degradation IV", "Oxidative Ethanol Degradation III", and "Ethanol Degradation II" -were inhibited in the ethanol groups. IPA predicted "ethanol" as an upregulated upstream regulator of the network with 22 downstream members for the 100 mM ethanol group only. Three members (NTRK2, TGFB3, and TLR8) were activated in all groups. Certain cellular functions were predicted to be changed dose-dependently. "Myocarditis" was dose-dependently inhibited, whereas "Cell death of heart cells" was dose-dependently activated. Several functions were inhibited in 50 mM ethanol only, eg, "Failure of heart" was enhanced in 50 mM ethanol only. Certain functions were activated in 100 mM ethanol only. "Cardiac fibrosis" was not predicted in any ethanol group. Conclusions: IPA predicted that ethanol-induced activation or inhibition of canonical pathways and functions of cardiomyocyte depended on ethanol concentration, and 3 networks related to heart functions for cardiomyocytes exposed to 3 concentrations of ethanol.

Background: In preparation for the 2021 Tokyo Olympic/Paralympic Games, the Japanese government assessed the risks of infectious disease outbreaks and identified necessary preparations. This present study reviewed efforts made during a previous measles epidemic and describes the roles of hospitals. Methods: This descriptive study investigated the records of 198 children with measles. All children were treated at a general hospital during the period from January 1997 through February 1998. We also examined the actions of pediatricians during and after a measles outbreak in the community. Results: Of the 198 children, 145 (73%) were hospitalized. The measles vaccination rate in the previous year was approximately 75%. Of the patients examined, 53% were younger than 2 years of age; mean age was 2.75 years. Pneumonia and gastroenteritis accounted for 46% and 30% of the complications, respectively. Issues requiring attention included the number of hospital beds located in a negative pressure room or private room with a window, the need for gamma globulin preparations with high measles antibody titers, the necessity of increasing vaccination opportunities, and extension of physician working hours. Conclusions: Visitors from other countries could cause measles outbreaks in Japan. Measures that might mitigate an outbreak were maintenance of high vaccination rates, ready availability of information on the location of negative pressure hospital rooms, knowledge of the status of the measle outbreak, and flexible medical staffing. There is a risk of measles outbreaks among infants and among those who do not have a measles antibody titer.

Background: Stroke is a leading cause of death and disability worldwide. Recently, secondary damage to the brain has been hypothesized as a key aggravating element in the ischemic cascade. However, the interaction between cerebral infarction and immune organs is not fully understood. In this study, we investigated changes in rat brain, spleen, thymus, mesenteric lymph node, and liver at 3, 7, and 13 days after transient middle cerebral artery occlusion (tMCAO) by immunohistochemistry. Methods: Rat models of stroke were made by tMCAO. Functional assessment was performed at 3 h and 1, 3, 5, 7, 9, 11, and 13 days after MCAO. Rat organs were harvested for 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry. Results: The number of CD8α⁺ T cells decreased in spleen, thymus, mesenteric lymph node, and liver and increased in brain. Numbers of Iba1⁺ and CD68⁺ macrophages decreased in spleen, thymus, and mesenteric lymph node and increased in brain and liver. Ki67⁺ cells exhibited the same characteristics as macrophages, and increased numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) -positive apoptotic cells were present in spleen, mesenteric lymph node, liver, and brain. Conclusions: The present results indicate that stroke is a systemic disease that, in addition to affecting the brain, also induces responses in immune organs. These results suggest that systemic treatment might be a good strategy for clinical stroke care.

Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland tumor that occurs mostly in the parotid gland. We report a case of EMC of the submandibular gland in a young man. The patient was aware of a slow-growing mass in the right submandibular gland for 1 year. Clinical examination and ultrasound confirmed a right submandibular mass, 2.5 × 3 cm² in size. Ultrasound-guided fine-needle aspiration indicated a diagnosis of pleomorphic adenoma, which was also suggested by magnetic resonance imaging. The submandibular gland tumor was excised. Immunohistochemical analysis showed carcinoma ex pleomorphic adenoma with a major epithelial-myoepithelial component. The patient was not treated with radiotherapy after surgery. No recurrence was observed during 24 months of follow-up. Because the morphology of EMC is similar to that of a benign tumor, it is frequently initially misdiagnosed. Surgery is always the most effective diagnostic and therapeutic measure for salivary gland tumors, especially those that grow slowly. Resection with negative margins is the treatment of choice for EMC; use of adjuvant radiotherapy is controversial.

Chylous ascites associated with radical resection of gastric cancer is a serious clinical condition. Lymph node dissection is indispensable during gastrectomy for gastric cancer. However, postoperative chylous ascites prolongs the hospital stay and re-operation. There are few reports on this subject. Most cases of chylous ascites resolve without treatment, but the condition can result in substantial morbidity. The definition of chylous ascites is ambiguous and varies in the English literature. In this report, we discuss a case of chylous ascites in a 68-year-old man who underwent distal gastrectomy for early gastric cancer at our hospital. He was admitted 8 months after surgery with a main complaint of abdominal swelling. Abdominal puncture helped to diagnose chylous ascites with marked elevation of triglyceride level. The patient received a hypercaloric infusion through a central line, and octreotide acetate, but did not improve. After assessment of lymph outflow by lymph scintigraphy, surgical ligation of the lymph vessels was performed through laparotomy. The volume of milky-white ascites in the abdominal cavity was 3,000 mL. Macroscopically, the fluid was confirmed as flowing from behind the common hepatic artery. Thus, ligation was performed. Chylous ascites has not recurred at 12 months after the re-operation. In summary, a case of chylous ascites after radical gastrectomy for gastric cancer was successfully treated by surgery. We review and discuss the relevant literature.

Rubinstein-Taybi syndrome is an extremely rare autosomal dominant genetic disorder that occurs in 1/125,000 and is characterized by distinctive facial appearance, short stature, mild to severe mental retardation, and higher risk for cancer. In addition, variable organ anomalies had been reported. Paraovarian cyst causing torsion of the ipsilateral fallopian tube is less common, with an estimated incidence of 1/1,500,000, but it can adversely affect tubal function. It occurs mainly in women in the reproductive age and is very rare in prepubescent girls. Here, we described the successful treatment of an extremely rare case of paraovarian cyst causing torsion of the ipsilateral fallopian tube in a patient with Rubinstein-Taybi syndrome. A 14-year-old girl with Rubinstein-Taybi syndrome was referred to our hospital for abdominal pain. Her medical history was unremarkable, except for moderate hirsutism and keloid scar. Physical examination revealed tenderness in the lower abdominal midline. The preoperative diagnosis was torsion of a left ovarian cyst. An exploratory laparoscopy was performed because of acute abdominal pain and revealed a left fallopian tube that was twisted twice due to an ipsilateral paraovarian cyst. The huge paraovarian cyst required laparotomy cystectomy, and the left ovary was preserved. Her postoperative course was uncomplicated. Preoperative diagnosis of paraovarian cysts can be difficult. The moderate hirsutism seen in our patient suggested the presence of a large paraovarian cyst due to androgen receptor-mediated effects. Therefore, Rubinstein-Taybi syndrome patients with hirsutism should be screened and assessed by pediatric surgeons for the presence of paraovarian cysts.

We report a case of contact dermatitis caused by both efinaconazole, a topical triazole antifungal drug, and luliconazole, a topical imidazole antifungal drug. Positive patch test reactions were observed with efinaconazole and luliconazole. A patch test with lanoconazole also elicited a positive reaction. We hypothesized that structural similarity between luliconazole and lanoconazole led to cross-reaction, and that the dithiolane ring common to both drugs or the structure of the vinyl imidazole with a dithiolane ring could be the antigenic determinant. Since efinaconazole and luliconazole have no common structures, patients could be sensitized to both drugs separately. The antigenic determinant of efinaconazole is unknown. However, the chemical formula of ravuconazole, an oral triazole antifungal drug, is similar to that of efinaconazole. Clinicians should carefully consider potential cross-reactivity between these drugs.

Objective: Various skin incision methods have been reported for reduction mammoplasty and mastopexy. This report describes a new incision method that may improve on conventional methods, particularly with respect to prevention of hypertrophic scars. Methods: We developed a comma-shaped incision method that results in fewer scars and less strain on the suture line. We then applied this new method to two cases, namely, one case of breast reduction and one case of breast fixation. Results: In both cases, we achieved good results. There was no scar at the inframammary fold, and no hypertrophic scar formation. All scars were within the breast area and were not in contact with the brassiere wire; hence, there was less pain after the operation. Conclusions: We developed a new incision method for reduction mammoplasty and mastopexy.

Posttraumatic malunion of the phalanx with rotational deformity may cause crossing of the finger and impair hand function. Cosmetic disfigurement and severe dysfunction of the fingers require surgical correction, most often via open corrective osteotomies and rigid fixation with plates. However, such an approach requires a longer incision, inevitably results in a scar, and has a higher potential for extensor tendon adhesions, which result in extension lags. In addition, abruption of the periosteum and plating of the phalanges require longer bone healing. This report describes the straightforward, minimally invasive correction of phalangeal malunions with a mini-external fixator. In this procedure, a digital block of the affected finger can be performed. The fully flexed position of all fingers provides accurate correction of phalangeal malunions. Although treatment of phalangeal malunions remains challenging, the present procedure is an alternative solution for phalangeal malunions.