Prognostic Analysis of Patients With Extramammary Paget Disease Treated With Conservative Excision.

BACKGROUND: Extramammary Paget disease (EMPD) is a malignant skin tumor with a relatively good prognosis. The standard treatment is wide local resection or Mohs micrographic surgery. However, conservative excision may be a better option when radical wide local excision is difficult to perform due to the patients' mental or physical condition. There have been no studies on the prognosis of patients with EMPD who underwent conservative excision. OBJECTIVE: To compare the prognosis of conservative excision cases to wide excision cases of EMPD. MATERIALS AND METHODS: The authors retrospectively analyzed the clinical data of 69 cases of EMPD without metastases to lymph nodes or organs (11 cases treated with conservative excision, 58 cases treated with wide local excision) who underwent resection of the primary tumor from 2002 to 2022 in the Department of Dermatology at Hokkaido University Hospital. RESULTS: The log-rank test showed no significant differences in overall survival or metastasis-free survival between the wide excision group and the conservative excision group, although conservative surgery was often chosen in elderly patients or patients with lower performance status. CONCLUSION: This study suggests that conservative surgery should be considered as a treatment option for EMPD.

Efficacy of a combination of paclitaxel and radiation therapy against cutaneous angiosarcoma: A single-institution retrospective study of 21 cases.

Cutaneous angiosarcoma (CAS) is a rare malignant tumor with a poor prognosis for which neither basic research on molecular pathomechanisms nor clinical prospective studies have progressed. A retrospective study of 28 CAS cases reported that chemoradiotherapy with taxanes was superior to conventional surgery. Since that time, chemoradiotherapy with paclitaxel (PTX + RT) has become a standard treatment. In this paper, we retrospectively investigate 21 cases of CAS that had been treated in the Department of Dermatology at Hokkaido University Hospital. Patients initially treated with PTX + RT followed by maintenance taxane chemotherapy showed better prognosis in overall survival (OS) and progression-free survival (PFS) (median OS, 28 months; median PFS, 12 months) compared to others (median OS, 10 months; median PFS, 5 months) (OS and PFS: p < 0.05, log-rank test). Our results are consistent with those of a previous study that suggested that PTX + RT followed by maintenance taxane chemotherapy is a better therapeutic option than other interventions, including surgery.

[Effects of Using the Adherence Score Sheet According to Application Timing in Improving Medication Adherence in SETSUYAKU-BAG Campaign].

Maintaining medication adherence is a critical issue in determining health outcomes in patients with chronic diseases. However, many patients do not adhere to their prescribed regimens. This study aimed to determine the effects of using adherence score sheets according to application timing in improving medication adherence among non-adherent outpatients. In community pharmacies, both patients and pharmacists evaluated medication adherence based on application timing (morning, noon, evening, and before going to bed) in 11 levels (0-10) for >4 months. A total of 58 outpatients were included in the study. The median scores among application timing at intermediate (patient 9.3, pharmacist 9.0) and final (patient 9.5, pharmacist 9.5) analyses were significantly higher than that at baseline (patient 7.6, pharmacist 7.0). At the end of the investigation, the ratio of non-adherent patients prescribed with hyperlipidemic medications was higher than those prescribed with medications for other lifestyle diseases. Approximately 80% of the patients reported improved medication adherence based on the questionnaires regarding their understanding on diseases and medications, medication awareness, and communication with pharmacists. Therefore, the utilization of an adherence score sheet according to application timing improved medication adherence of patients with chronic diseases.

[Assessing the Effects of Prescription Adjustment and Medication Non-adherence Associated with Medication Efficacy Classifications from Leftover Drugs through the SETSUYAKU-BAG Campaign].

　The increase in medical expenditure has been worsening and poses a serious social problem. Commonly, leftover drugs are retained by patients. We estimated the possible reduction in prescription rates by appropriately reusing leftover drugs, and investigated the medication efficacy classifications that render leftover drugs due to the medication non-adherence. A retrospective cross-sectional survey of prescription data was performed at community pharmacies engaged in the appropriate reuse of leftover drugs through the SETSUYAKU-BAG campaign. We evaluated the drug costs and number of drugs originally prescribed, the reduction in expenditure and numbers after the use of leftover drugs, and then calculated the prescription reduction ratio (PRR) based on the number of drugs. Factors contributing to non-adherence were analyzed by the PRR. After reviewing the prescription information of 1792 patients, the reduction rate in drug expenditure was found to be 20.1%. Purgatives, Chinese medicines, and agents for peptic ulcer had higher PRRs and belonged to the top ten medications according to the prescription efficacy classifications. Non-adherence associated with the medication efficacy classifications was assessed by analyzing 5466 formulations. Thirty percent of formulations were found to be non-adherent. According to the medication efficacy classifications, six medications including agents for hyperlipidemias, peptic ulcer, psychotropics agents, and others, were less adherent than antihypertensives. These results suggest that adjusting prescriptions by appropriately reusing leftover drugs in community pharmacies could reduce medical costs. Further considerations are necessary for improving medication adherence in Japan. Healthcare providers should monitor medication adherence more carefully, with the results identified in this study.

Prescription Factors Associated with Medication Non-adherence in Japan Assessed from Leftover Drugs in the SETSUYAKU-BAG Campaign: Focus on Oral Antidiabetic Drugs.

BACKGROUND: Medication adherence has an important influence on health outcomes in patients with chronic diseases. However, few studies have been performed in Japan to determine factors related to medication non-adherence. OBJECTIVE: The aim of this study was to identify prescription factors related to medication non-adherence by investigating patient characteristics, all prescriptions, and prescriptions for oral antidiabetic drugs (OADs). METHODS: A retrospective cross-sectional survey of prescription data about implementation of dosing regimen was performed at community pharmacies engaged in appropriate use of leftover drugs. We evaluated the amount of drugs originally prescribed and the reduced amount after use of leftover drugs, and then calculated prescription reduction ratio (PRR). We analyzed prescription factors contributing to non-adherence based on the PRR. RESULTS: Prescription information for 1207 patients was reviewed, revealing that patients were non-adherent to 58% of prescriptions. Lack of a drug copayment, fewer concurrent drugs, and drugs not in single-dose packaging were associated with non-adherence. Among the 1207 patients, 234 prescriptions for diabetes and 452 OAD formulations were included. Forty-seven percent of prescriptions and 29% of the formulations were non-adherent. A higher dosing frequency and preprandial administration were associated with non-adherence. Among the OADs, adherence was lower for α-glucosidase inhibitors and biguanides than for sulfonylureas. CONCLUSIONS: Several factors related to patient characteristics, general drug prescriptions, and OAD prescriptions were associated with non-adherence. Further consideration will be needed to improve adherence to medication in Japan. Health care providers should perform more careful monitoring of adherence in patients with the factors identified by this study.

[A systematic review of decided litigated cases on adverse drug events in Japan: classification of decided cases appearing in law reports].

Much of the damage to health caused by drugs could be prevented by appropriate care. A well-defined duty of care and further information are required for healthcare professionals. Although there are many litigation cases to use as references, neither the extent of the duty of care nor the obligation to explain medication according to the type of drug prescribed has yet been fully established. Thus, we systematically collected decided cases of adverse drug events, and assessed the degree of the duties of care and information. Specifically, we collected decided cases in which physicians, dentists, pharmacists, nurses, or hospitals had been sued. Data were derived from Bessatsu Jurist Iryo-kago Hanrei Hyakusen, Hanrei Jihou, and Hanrei Times from 1989 to November 2013, and information on precedents in the records of the Supreme Court of Japan from 2001 to November 2013. We analyzed the cases, and assessed the following according to the type of drug: (1) standards and explanations when dealing with drugs that were critical issues in litigation, and (2) the degree of the physician's or pharmacist's duties of care and information. In total, 126 cases were collected. The number of drug categories classified was 27, and 9 were considered of practical importance. After this systematic review, we found a trend in the degree of the required level of care and information on several drugs. With respect to duties of care and information, the gap between the required level and actual practice suggests that healthcare professionals must improve their care and explanations.

Biosynthesis of the structurally unique polycyclopropanated polyketide-nucleoside hybrid jawsamycin (FR-900848).

The biosynthetic gene cluster of antifungal agent jawsamycin (FR-900848) has been identified by heterologous expression. A series of gene inactivations and in vitro and in vivo analysis of key enzymes in the biosynthetic pathway established their functions. A novel mechanism involving a radical S-adenosyl methionine (SAM) cyclopropanase collaborating with an iterative polyketide synthase is proposed for the construction of the unique polycyclopropanated backbone. Our reconstitution system sets the stage for studying the catalytic mechanism of this intriguing contiguous cyclopropanation.

[SETSUYAKU-BAG Campaign--investigation of outpatient's leftover drugs and promotion of proper reuse of leftover drugs to reduce medical expenses].

Pharmacists, being compensated through the new dispensing fee, are required to educate patients on their adhesion to the use of prescribed drugs, and to inventory the levels of leftover drugs in outpatients. Recently, Fukuoka City Pharmaceutical Association started a campaign for regulating leftover drugs (Setsuyaku Bag Campaign). Thirty-one pharmacies joined the campaign. Pharmacists distributed convenience bags, called 'SETSUYAKU-BAG.' The patients put their leftover drugs in the bags and brought them to community pharmacies. The pharmacists inventoried the returned drugs and reported their results to the doctors. The doctors adjusted the prescriptions accordingly. We counted and analyzed old and new inventories. The number of leftover drugs was 252, for a total value was ¥839655. Cost of leftover drug prescriptions could be reduced by ¥702695, and the value of drugs thrown away was ¥94801. In total, we could reduce the amount of leftover drugs by 83.7%. The cost of leftover drug for one dose package (ODP) is higher than that for non-ODP. However, there were no significant differences in results per age, sex, number and kinds of drugs, prescription days and premium contribution rate. These results suggest that prescription regulation by inventory of leftover drugs in community pharmacies could significantly reduce overall medical expenses. Further studies are necessary in order to account for patients' health, and to establish more efficient patient education to raise outpatients' adherence to the new programs.

Expression of hypoxia-inducible protein 2 in renal cell carcinoma: A promising candidate for molecular targeting therapy.

This study investigated the expression of hypoxia-inducible protein 2 (HIG2), a novel renal cell carcinoma (RCC)-associated molecule and an essential growth factor for RCC, in kidneys to elucidate its clinical significance in RCC. An immunohistochemical study of HIG2 was conducted in 93 surgical samples of RCC tissues and 10 samples of normal kidney tissues obtained after nephrectomies for localized RCC. HIG2 expression was also correlated with clinicopathological characteristics and survival. Only faint or weak immunostaining for HIG2 was observed in normal kidney samples. HIG2 expression was found in 86% of RCC tissues (80/93). When analyzed by histological type, positive staining for HIG2 was detected in all papillary (7/7), chromophobe (1/1) and cyst-associated (3/3) RCC. In contrast, the HIG2 expression was observed in 85% of clear cell (68/80) and 50% of spindle cell (1/2) RCC. Labeling indices were 74.1, 45.4, 39, 24.8 and 12.1% in papillary, spindle, clear cell, cyst-associated and chromophobe RCC, respectively. A significant increase in HIG2 expression was noted in RCC tissues obtained from patients with high stage RCC, lymph node metastasis and high nuclear grade (p<0.001, p<0.02 and p<0.006, respectively). RCC patients with a negative HIG2 staining had prolonged 5-year cancer-specific survival. In conclusion, HIG2 expression was extensively observed in RCC tissues and was higher in advanced RCC, suggesting that HIG2 is a candidate for the development of molecular targeting therapy.

Unprecedented biological cyclopropanation in the biosynthesis of FR-900848.

We were able to show the predominant incorporation of a single enantiomer and intact incorporation of multiply labelled synthetic diketide precursors (and), which established the intermediacy of cyclopropanated diketide and led to our proposal for the unprecedented biological cyclopropation, via PKS (polyketide synthase) having a novel cyclopropanase domain, in the biosynthesis of FR-900848 (1).

Myxoma of the kidney.

A 62-year-old man had a right renal mass incidentally diagnosed by ultrasonography. Magnetic resonance imaging revealed a well-defined right renal mass with homogenous low-signal intensity on the T(1)-weighted pulse sequence and heterogeneous high-signal intensity on the T(2)-weighted pulse sequence. A right nephrectomy was performed. The histological examination showed a myxoma, which is a very uncommon neoplasm in the kidney. Eight cases have been reported previously.

Neonatal abdominal wall urinoma due to rupture of anterior urethral diverticulum.

An anterior urethral valve with diverticulum is an uncommon cause of congenital urethral obstruction and urinary extravasation compared with a posterior urethral valve. We report a neonate presenting with an abdominal wall urinoma caused by rupture of an anterior urethral diverticulum. Urine drainage via urethral catheter was effective to resolve the abdominal urinoma. Voiding cystourethrogram performed 6 months after an endoscopic incision of the distal margin of the diverticulum revealed a normal urethra with smooth voiding. To our knowledge, no similar case has been reported previously.

[Central and peripheral nerve disorder induced by interferon alpha therapy for renal cell carcinoma].

Interferon alpha (IFN-alpha) therapy was conducted for a male patient aged 70 years old, who underwent a two-stage radical nephrectomy for bilateral renal cell carcinoma with multiple pulmonary metastasis. He was hospitalized due to leg weakness and disorientation 45 days after this treatment was started. We discontinued INF-alpha therapy immediately after neurologists indicated the disorder of the central and the peripheral nervous systems induced by the administration of this cytokine. Steroid pulse therapy was effective to resolve the patient's neurological symptoms. To our knowledge, this is the first case of the side effects on both central and peripheral nervous systems by IFN-alpha therapy for renal cell carcinoma.