Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

Multisite Partial Glycosylation Approach for Preparation of Biologically Relevant Oligomannosyl Branches Contribute to Lectin Affinity Analysis.

High-mannose-type glycans play essential biological roles, e.g., immune response and glycoprotein quality control, and preparing a series of oligomannosyl branches of high-mannose-type glycans is critical for biological studies. However, obtaining sufficient amounts of the various oligomannosyl branches is challenging. In this study, we demonstrated a partial glycosylation strategy for the single-step synthesis of various biologically relevant oligomannosyl-branched structures. First, Manα1-6(Manα1-3)Man-type oligomannosyl branch was synthesized via double glycosylation from a 3,6-di-OH mannosyl acceptor and fluorinated mannosyl donor with perfect α-selectivity. Subsequent partial glycosylation by reducing the equivalent of the mannosyl donor enabled to obtain biologically relevant Manα1-2Manα1-6(Manα1-2Manα1-3)Man, Manα1-6(Manα1-2Manα1-3)Man, Manα1-2Manα1-6(Manα1-3)Man, and Manα1-6(Manα1-3)Man in one-pot. Each oligomannosyl branch could be easily purified by liquid chromatography. The resulting structural isomers were identified by 2D-HMBC NMR. A systematic lectin affinity assay using the prepared oligomannosyl branches showed different specificities for the Galanthus nivalis lectin between structural isomers of the oligomannosyl branches with the same number of mannose residues..

[Complete Pathological Response of Rectal Cancer with Preoperative Chemoradiotherapy-A Case Report].

A 79-year-old man diagnosed with rectal cancer and underwent preoperative chemoradiotherapy. After chemoradiotherapy, the patient underwent abdominoperineal resection. Postoperative pathological examination confirmed pathological complete response. Postoperatively, the patient developed a pelvic abscess due to wound infection from the anal fistula, which required drainage and antibiotic therapy. Treatment options that include a watch and wait approach are required in cases of resectable lower rectal cancer with a high risk of local recurrence that has shrunk after preoperative chemoradiation.

[Long-Term Complete Response following Chemotherapy for Advanced Gastric Cancer in an Elderly Patient].

A 78-year-old man was diagnosed with HER2-positive advanced gastric cancer, cT3N2M1(LYM: #16a1, 16b1), cStage ⅣB, after being referred for anemia. The lesion was deemed unresectable, and first-line chemotherapy was initiated using S-1, cisplatin(CDDP), and trastuzumab(T-mab). After 2 courses of chemotherapy, the patient developed febrile neutropenia( Grade 3). At this point, the lesion showed partial response(PR), and chemotherapy was continued using oral S-1 as a single agent. After 3 months of S-1 monotherapy, the para-aortic lymph node metastases showed a complete response (CR). S-1 monotherapy was continued without major adverse events for 2 years, and the patient is presently alive and well 6 years after obtaining clinical CR. This may suggest that S-1 is a safe and effective treatment for unresectable advanced gastric cancer in elderly patients.

Evaluation of Nosocomial Infection Control Measures to Minimize the Risk of Aspergillus Dispersion During Major Demolition Work: A Case Study of a Japanese University Hospital.

OBJECTIVES: To verify the effectiveness of our infection control measures based on the infection control risk assessment (ICRA) to minimize the risk of Aspergillus dispersion before, during, and after demolition work in a university hospital. BACKGROUND: It is widely accepted that invasive aspergillosis is associated with construction, renovation, and demolition activities within or close to hospital sites. However, the risk is underestimated, and only limited preventive measures are taken in Japanese hospitals. METHOD: The demolition process, carried out in July 2014, was supervised by our facility management in collaboration with the infection prevention team and followed an adapted ICRA tool. Dust containment measures were implemented to reduce the risk of airborne Aspergillus contamination. Air sampling was performed at four wards in the adjacent hospital buildings to assess the containment measures' effectiveness. RESULTS: A high, undetermined number of colonies of bacteria and molds were detected on all outside balconies before demolition. During demolition, Aspergillus spp. was detected only in the ward closest to the demolition site. However, no case of aspergillosis was reported. The difference-in-difference analysis revealed that the interaction between the demolition activity, height of the ward, and distance of the air intake to the demolition activities resulted in a significant increase in the numbers of Aspergillus spp. CONCLUSIONS: When large-scale demolition work occurs in hospital premises, Aspergillus spp. may increase in the ward where the vertical and horizontal distance of air intake from the demolition site is close, even though infection control measures based on the ICRA are implemented.

Differences in Adverse Drug Events Among Pediatric Patients With and Without Cancer: Sub-Analysis of a Retrospective Cohort Study.

OBJECTIVES: This study investigated the differences in the incidence and severity of adverse drug events (ADEs) in pediatric patients with and without cancer. METHODS: We used data from the Japan Adverse Drug Events Study for pediatrics, a cohort study enrolling pediatric inpatients at two tertiary care teaching hospitals in Japan. ADEs were identified by on-site review of all medical charts, incident reports, and prescription queries by pharmacists. Two independent physicians reviewed all potential ADEs and classified ADEs in terms of severity and class of causative medication. We compared the incidence and characteristics of ADEs between pediatric cancer patients and non-cancer patients. RESULTS: We enrolled 1189 patients during the study period, 27 with cancer and 1162 without cancer. We identified 480 ADEs in 234 patients (20%): 191 ADEs among 21 cancer patients and 289 ADEs among 213 non-cancer patients (7.1 per patient vs. 0.25 per patient, respectively; p < 0.0001). The most common medications associated with ADEs in cancer patients were antitumor agents; in contrast, medications associated with fatal or life-threatening ADEs in cancer patients were most often sedatives (25%) and blood products (25%). Medications associated with fatal or life-threatening ADEs among non-cancer patients were most often sedatives (15%). The percentages of fatal or life-threatening ADEs in cancer patients and non-cancer patients were 2.1 and 4.5%, respectively. CONCLUSIONS: Pediatric patients with cancer have a higher risk for ADEs. Although the overall severity was similar between patients with and without cancer, the most common classes of causative medication and medications associated with a higher rate of severe ADEs differed. Application of this information may help minimize the impact of ADEs in pediatric patients.

Bacteremia secondary to Alloscardovia omnicolens urinary tract infection.

A 70-year-old woman was admitted to our hospital with malaise, bilateral leg edema, and oliguria. She had a history of advanced uterine cancer. Bilateral double-J catheters were inserted because growth of intra-abdominal metastases led to bilateral ureteral stricture and hydronephrosis. Two days later, she suddenly developed high fever. Thin gram-positive bacilli of moderate length were detected in the anaerobic blood culture bottles. We performed 16S ribosomal RNA analysis of the isolate and it showed 100% match with Alloscardovia omnicolens DSM 21503(T). She was successfully treated with cefmetazole in addition to percutaneous nephrostomy.

A first case of isolation of Kerstersia gyiorum from urinary tract.

An 82-year-old man with percutaneous nephrostomy presented to our Hospital with dysuria for one day. The patient's percutaneous nephrostomy tube was exchanged, with about 20 mL of creamy purulent urine being collected. Direct smear of the urine specimen showed polymorphonuclear leukocytes and small Gram-negative bacilli, some of which had undergone phagocytosis. This organism was identified as Kerstersia gyiorum using 16S ribosomal RNA gene analysis. He was successfully recovered with exchange of his percutaneous nephrostomy tube and fluoroquinolone internal use treatment. This is the first case report of urinary tract infection due to K. gyiorum.

Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.

In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or ß-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by µ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety.

Serotype 35B Streptococcus pneumoniae, Japan, 2002-2012.

Among 641 pneumococcal isolates recovered from 2002 to 2012 in Japan, 19 (3.0%) were serotype 35B. Twelve of the 19 were ST558 (single-locus variant of Utah35B-24-ST377) and seven were ST2755. Continuous monitoring of serotypes and their clonal association is important, especially in Japan where PCV7 was licensed only in 2010.

Effects of raloxifene on brachial arterial endothelial function, carotid wall thickness, and arterial stiffness in osteoporotic postmenopausal women.

The beneficial effects of raloxifene, a selective estrogen receptor modulator, on cardiovascular risks and events have been investigated. Brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and pulse wave velocity (PWV) have been widely used in clinical settings as surrogate markers of atherosclerosis. This study investigated the simultaneous effects of raloxifene on brachial arterial FMD, carotid IMT, and PWV in osteoporotic postmenopausal women. A total of 31 postmenopausal women with osteoporosis or osteopenia were divided into 2 groups: a raloxifene group (n = 15; mean age +/- SD, 66.1 +/- 8.2 years) was treated with raloxifene hydrochloride (60 mg/day) orally for 12 months, and an untreated control group (n = 16; 64.1 +/- 7.8 years). Brachial arterial FMD, carotid IMT, and brachial-ankle PWV (baPWV) were measured at baseline and at 12 months after the start of the study. The brachial arterial FMD increased significantly, from 4.5 +/- 1.8% to 9.2 +/- 3.0%, in the raloxifene group (P < 0.01) but did not change in the control group. Nitroglycerin-induced vasodilatation did not change in either group. The carotid IMT decreased significantly, from 0.82 +/- 0.15 mm to 0.72 +/- 0.11 mm, in the raloxifene group (P < 0.01) but did not change in the control group. The baPWV did not change in either group. In conclusion, raloxifene may have beneficial effects on brachial arterial endothelial function and carotid wall thickness in osteoporotic postmenopausal women.

Ten-year patency and factors causing restenosis after endovascular treatment of iliac artery lesions.

BACKGROUND: Long-term outcome and the factors associated with restenosis after endovascular treatment (EVT) for iliac artery lesions in peripheral arterial disease (PAD) were evaluated. METHODS AND RESULTS: EVT was performed for 487 lesions (TransAtlantic Inter-Society Consensus-II (TASC-II) Type-A: 275, B: 115, C: 37, and D: 60) in 436 PAD patients. The initial success rates for Type-B and Type-D lesions were lower than for Type-A lesions (P<0.05). The 3-, 5- and 10-year patency rates were 67%, 54% and 50%, respectively, with plain-old balloon angioplasty (POBA), and 88%, 82% and 75%, respectively, for stenting after suboptimal POBA, showing a significantly higher patency after treatment with a stent (P<0.001). With POBA, the long-term patency for Type-C/D lesions was lower than for Type-A/B lesions (P<0.05), but the patency after stenting did not differ significantly between Type-C/D and A/B. In the univariate analysis, the TASC-II classification, lesion length, pre- and post-procedural stenosis rates and stent use were found to be significant factors associated with restenosis (P<0.05). In the multivariate analysis, stent use (hazard ratio (HR) 0.345, confidence interval (CI) 0.193-0.616, P<0.001) and the post-procedural stenosis rate (HR 1.015, CI 1.001-1.030, P<0.05) were significantly associated with restenosis. CONCLUSIONS: Stent use and a low residual stenosis rate are significantly associated with patency, and favorable long-term patency can be obtained with stent placement for selected TASC-II Type-C/D lesions.

Effects of antiplatelet agents and other factors on neointimal proliferation in iliac artery stenting: intravascular ultrasound analysis.

OBJECTIVE: To use intravascular ultrasound to investigate the effects of antiplatelet agents and other factors on neointimal proliferation after stent implantation for iliac artery stenosis. PATIENTS AND METHODS: The subjects were 109 patients with peripheral arterial disease who underwent stent implantation in the iliac artery. Intravascular ultrasound was performed to evaluate lesion area, stent dilatation and neointimal proliferation before, just after, and six months after stenting. Multiple regression analysis was performed to examine the relationship of the neointimal proliferation rate with antiplatelet agents and other factors. RESULTS: At the time of stent implantation, a Palmaz stent resulted in a significant increase in lumen area compared with a Wallstent (p < 0.05). Six months later, self-expanding Wallstent and Luminexx stents showed a significant increase in the stent-lumen area (p < 0.05). The neointimal proliferation rate showed a significant negative correlation with beraprost and cilostazol (p < 0.05) and a significant positive correlation with serum creatinine (p < 0.01). There was no significant difference in the vessel lumen area including the proliferated intima among the three stents. CONCLUSION: Suppression of neointimal proliferation can be achieved with beraprost or cilostazol whereas renal dysfunction may increase neointimal proliferation following stent implantation in iliac artery lesions.

[A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep].

UNLABELLED: In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).

Molecular typing of methicillin-resistant Staphylococcus aureus by PCR-RFLP and its usefulness in an epidemiological study of an outbreak.

A new convenient molecular typing method, simultaneous polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis, for three different genes of methicillin-resistant Staphylococcus aureus (MRSA) was evaluated using 35 isolates of MRSA and comparing results with those previously reported for sequencing-based spa typing. Twenty-nine isolates of the most frequent protein A (spa) type were discriminated into 6 different types by PCR-RFLP. In contrast, spa typing could discriminate only 1 of the 19 most frequent PCR-RFLP-type isolates. The discriminatory powers of the two methods were equal for the other isolates. These results suggest that PCR-RFLP has the advantages of both relative easiness and greater discriminatory power than spa typing. We also report the case of a suspected outbreak in which PCR-RFLP was sufficient for ruling out the possibility of an outbreak. Thus, PCR-RFLP is preferable as a preliminary screening method for epidemiological studies of nosocomial infection caused by MRSA.

Development of a radon trap device using a corona discharge.

Radon is one of the noble gases, which are chemically inert and do not make any reactants under normal conditions. In this experiment we demonstrated an enigmatic reaction between radon and fluorine when a corona discharge is used as a promoter. Distinctive changes in radon concentrations were caused by the discharge and a trap efficiency of >99.5% was estimated. The mass balance between the trapped and the released radon was found to be reasonable. This indicates the existence of chemical reactions with radon. This trap phenomenon has application as a technique for reducing radon concentration in radon-contaminated air. It is possible that this technique will be applicable to other noble gases.