Safety comparisons among monoamine oxidase inhibitors against Parkinson's disease using FDA adverse event reporting system.

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.

Identification of Factors Contributing to Methadone-Induced Daytime Sleepiness in Cancer Patients and Proposal of the Conversion Ratio from Other Opioids to Oral Methadone: A Retrospective Cohort Study.

Background: When methadone is used to treat cancer pain, the Japanese health insurance system recommends to determine the starting dose according to the equivalency conversion table based on the morphine-equivalent daily dose (MEDD) of prior opioids proposed by the National Comprehensive Cancer Network. Owing to the wide range in variability of the conversion table, methadone increases the incidence of daytime sleepiness. Objective: To identify the factors associated with daytime sleepiness and propose a conversion ratio from pretreatment MEDD to oral methadone that decreases the risk of daytime sleepiness. Design: Retrospective cohort study. Setting/Subjects: One hundred patients who started oral methadone to relieve cancer pain at Ashiya Municipal Hospital (Hyogo, Japan) from January 1, 2013, to August 31, 2022, were enrolled. Measurements: The primary endpoint, the conversion ratio from pretreatment MEDD to oral methadone without daytime sleepiness, was determined using receiver operator characteristic (ROC) curve analysis. Results: The incidence of daytime sleepiness within seven days of methadone initiation was 40.0%. The factors identified as contributing to daytime sleepiness were pretreatment MEDD (odds ratio [OR]: 0.941, 95% confidence interval [CI]: 0.916-0.966, p <0.001) and methadone dose (OR: 1.395, 95% CI: 1.178-1.652, p <0.001). The conversion ratio from pretreatment MEDD to oral methadone was 0.24, with an area under the ROC curve of 0.909 (p <0.001). Conclusions: Daytime sleepiness developed when methadone dose is high relative to pretreatment MEDD. To the best of our knowledge, this is the first study to suggest the conversion ratio from pretreatment MEDD to oral methadone without causing daytime sleepiness.

Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis.

BACKGROUND: Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HT3RAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HT3RA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HT3RAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis. METHODS: We retrospectively analyzed the effect of 5-HT3RAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HT3RAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database. RESULTS: In a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HT3RA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169-0.472). CONCLUSIONS: The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HT3RAs in patients with the triple antiemetic therapy.

Naldemedine-laxative combination: retrospective inpatient study.

OBJECTIVES: The initiation of peripherally acting µ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting. METHODS: This retrospective study evaluated 93 inpatients who received at least four doses of naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before naldemedine administration and the incidence of diarrhoea. RESULTS: Daily defecation counts during the first 7 days after compared with before naldemedine administration were greater in both the naldemedine, magnesium oxide (MgO) and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. The incidence rates of diarrhoea were significantly higher in the naldemedine, MgO, and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. CONCLUSIONS: The introduction of naldemedine alone or in combination with MgO should be considered.

Proton Pump Inhibitors Ameliorate Capecitabine-induced Hand-Foot Syndrome in Patients With Breast Cancer: A Retrospective Study.

BACKGROUND/AIM: Hand-foot syndrome (HFS) is the most common adverse event associated with capecitabine, and its pathogenesis is known to be associated with inflammation. Proton pump inhibitors (PPIs) reportedly exert anti-inflammatory effects; however, the impact of PPIs on capecitabine-induced HFS needs to be clarified in the clinical setting. In the present study, we retrospectively investigated the efficacy and safety of PPIs in patients with breast cancer receiving capecitabine. PATIENTS AND METHODS: We analyzed the effects of PPIs on the development of severe HFS (grade ≥2), progression-free survival (PFS), and overall survival (OS) in 195 patients who received capecitabine chemotherapy for breast cancer. RESULTS: In total, 50 patients (26%) were treated with PPIs, while 145 patients (74%) did not receive PPIs. The incidence of severe HFS was significantly lower in patients who received PPIs (18%) than in patients who did not receive PPIs (43%, p=0.001), and the discontinuation rate of capecitabine therapy due to HFS was also lower in patients receiving PPIs than in those who did not receive PPIs (p=0.003). Multivariate analysis revealed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of severe HFS (odds ratio (OR)=0.265, p=0.003). Meanwhile, no significant difference in median PFS and OS values was observed between patients treated with and without PPIs. CONCLUSION: Concomitant use of PPIs could ameliorate capecitabine-induced HFS in patients with breast cancer.

Tapentadol in Cancer Patients with Neuropathic Pain: A Comparison of Methadone, Oxycodone, Fentanyl, and Hydromorphone.

Tapentadol has µ-opioid receptor stimulating and noradrenaline reuptake inhibiting properties, and should be effective for neuropathic pain (NP). However, the efficacy of tapentadol for NP in cancer patients is unclear. Ashiya Municipal Hospital (Hyogo, Japan) enrolled five groups of Japanese cancer patients between January 1, 2013, and December 31, 2019. Patients with NP were administered tapentadol (n = 29), methadone (n = 32), oxycodone (n = 20), fentanyl (n = 26), or hydromorphone (n = 20). The primary endpoint was the difference in the verbal rating scale (VRS) scores between days 0 and 7. The secondary endpoint was the tolerability of each opioid. Before administering opioids among the five groups, there was no significant difference in the VRS score (p = 0.99). The mean reduction in the VRS score on day 7 was significantly greater in the tapentadol group than in the oxycodone group (p = 0.0024) and was larger than that of the methadone, fentanyl, and hydromorphone groups. Regarding safety, the discontinuation rate in the tapentadol group was the lowest of all groups (tapentadol vs. methadone vs. oxycodone vs. fentanyl vs. hydromorphone, 0.0% vs. 6.3% vs. 5.0% vs. 3.8% vs. 10.0%, respectively). This study suggests that tapentadol could be efficacious for cancer patients with NP, and a preferred option in cases that require immediate dose adjustment or for those at high risk for adverse effects. However, the pain intensity was evaluated without pain assessment scales specific to NP. Thus, we think that it is desirable to validate our findings using assessment scales, such as the painDETECT questionnaire in future.

Remote Reminiscence Using Immersive Virtual Reality May Be Efficacious for Reducing Anxiety in Patients with Mild Cognitive Impairment Even in COVID-19 Pandemic: A Case Report.

To prevent cognitive decline, non-pharmacological therapies such as reminiscence for mild cognitive impairment (MCI) are required, however, the use of nursing homes was limited due to coronavirus disease 2019 (COVID-19). Therefore, the demand for remote-care is increasing. We hypothesized that immersive virtual reality (iVR) could be used more effectively than conventional reminiscence for anxiety. We first examined the effectiveness and safety of reminiscence using iVR (iVR reminiscence session) in patients with MCI. After COVID-19 imposed restriction on visiting nursing homes, we conducted online iVR reminiscence session (remote iVR reminiscence session) and compared its effectiveness with that of interpersonal iVR reminiscence session (face-to-face iVR reminiscence session). The results of two elderly with MCI suggested that iVR reminiscence could reduce anxiety and the burden of care without serious side effects. The effects of remote iVR reminiscence might be almost as effective as those of face-to-face one.

A Pilot Study to Develop a New Method of Assisting Children in Taking Their Medication by Using Immersive Virtual Reality.

Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (quinine 0.00375%) while viewing two different VR images (strawberry sponge cake and orange juice) alternately and received sensory tests immediately after the tasting and again 30 s later. In addition, nausea was assessed 30 s after tasting for each VR image. The primary endpoint was the difference in sensory test scores immediately after the tasting and 30 s later, between the two images. There were no significant differences in the sensory test scores between the placebo and either strawberry sponge cake or orange juice immediately after tasting. However, 30 s after tasting, the scores changed significantly to a tendency to perceive sweetness from the strawberry sponge cake and orange juice images compared with the placebo. No subject experienced nausea. Therefore, the findings of this study suggest that displaying images of sweet foods by using iVR to stimulate visual perception could safely reduce the sense of bitterness.

Skin disorder management in oral anticancer drugs by collaboration of hospital pharmacists and community pharmacists.

BACKGROUND: In Japan, the multidisciplinary team approach in cancer chemotherapy has become quite widespread. However, patients treated with oral anticancer drugs in outpatient clinics usually receive short medical examinations from doctors without any intervention of pharmacists. To improve this medical circumstance, we made a skin disorder manual for community pharmacists and evaluated its feasibility. METHODS: Patients who underwent oral skin toxic chemotherapy from May 1, 2017, to October 31, 2017, were enrolled. The severity of skin toxicities was evaluated based on NCI-CTCAE ver4.0. Skin care and skin disorders were assessed by community pharmacists based on the assessment document arranged by the investigator. Numbers of patients who replied to the assessment, numbers of replies, numbers of assessments and instructions for skin care, and numbers of prescription proposals were evaluated to assess the value of intervention of community pharmacists. RESULTS: Sixty-two patients were enrolled in this study. Community pharmacy responded to 55 patients (88.7%), for a total of 335 replies. The data described in the replies were as follows: 317 assessments of skin disorders (94.6%), 307 assessments of skin care (91.6%), 248 instructions for skin care (74%), and 19 prescription proposals (5.7%). CONCLUSIONS: Community pharmacists have high motivation for prevention and early detection of skin disorders. Although the number of prescription proposals is small, some proposals have contributed to improving side effects. Collaboration of hospital pharmacists and community pharmacists is important for prevention, early detection, and treatment of skin disorders caused by oral anticancer drugs.

Knowledge, attitudes, and practices toward COVID-19 among university students in Japan and associated factors: An online cross-sectional survey.

The coronavirus disease (COVID-19) pandemic has greatly altered peoples' daily lives, and it continues spreading as a crucial concern globally. Knowledge, attitudes, and practices (KAP) toward COVID-19 are related to individuals' adherence to government measures. This study evaluated KAP toward COVID-19 among university students in Japan between May 22 and July 16, 2020, via an online questionnaire, and it further investigated the associated determining KAP factors. Among the eligible respondents (n = 362), 52.8% were female, 79.0% were undergraduate students, 32.9% were students whose major university subjects were biology-related, 35.4% were from the capital region, and 83.7% were Japanese. The overall KAP of university students in Japan was high. All respondents (100%) showed they possessed knowledge on avoiding enclosed spaces, crowded areas, and close situations. Most respondents showed a moderate or higher frequency of washing their hands or wearing masks (both at 96.4%). In addition, 68.5% of respondents showed a positive attitude toward early drug administration. In the logistic regressions, gender, major subjects, education level, nationality, residence, and psychological factors (private self-consciousness and extroversion) were associated with knowledge or attitudes toward COVD-19 (p < 0.05). In the logistic and multiple linear regressions, capital regions, high basic knowledge, high information acquisition, correct information explanations contributed positively to preventative action (p < 0.05). Non-capital regions, male gender, non-bio-backgrounds, high public self-consciousness, high advanced knowledge, incorrect information explanations, and high extroversion contributed negatively to self-restraint (p < 0.05). Moreover, self-restraint was decreasing over time. These findings clarify the Japanese university students' KAP and the related factors in the early period of the COVID-19 pandemic, and they may help university managers, experts, and policymakers control the future spread of COVID-19 and other emerging infections.

The Adequateness of Methadone for Japanese Terminal Cancer Patients Can Be Determined Earlier than 7 Days: A Preliminary Retrospective Study.

INTRODUCTION: The Japanese packaging instructions for methadone prohibit dose escalation within 7 days of administration initiation as this may result in overdose and subsequent adverse events. However, for terminal cancer patients, evaluation of the effects of methadone may be desirable within 7 days because they have limited prognoses. We aimed to determine the possibility of estimating the adequateness of methadone earlier than the 7th day by investigating the onset timing of analgesic effects and adverse events of methadone in Japanese terminal cancer patients. METHODS: Japanese terminal cancer patients who started taking methadone in Ashiya Municipal Hospital were enrolled from January 1, 2013 to February 28, 2019. Verbal rating scale (VRS) scores on pain and adverse events before and after methadone administration (on days 3, 5, and 7) were retrospectively investigated from medical records. RESULTS: We enrolled 25 patients, of which 20 (80.0%) received methadone until day 7. The VRS score (mean ± standard deviation) on pain was significantly reduced to 0.90 ± 0.55 on day 3, compared with 1.65 ± 0.67 before the administration of methadone (p < 0.05). The mean VRS scores did not differ significantly on days 3, 5, and 7. Additionally, of the 23 patients who received methadone until day 3, 20 (87.0%) showed an analgesic effect on day 3 and 17 (85.0%) received methadone without experiencing serious adverse events until day 7. CONCLUSIONS: The adequateness of methadone in Japanese terminal cancer patients could be determined before day 7, considering the high analgesia incidence and few adverse events 3 days after the methadone administration under careful observation by a physician experienced in methadone administration. However, as this is a preliminary study, the relationship between pharmacokinetic parameters and analgesic effects was not evaluated. Further studies involving pharmacokinetics and multicenter prospective studies are required to support these findings.

Immersive Virtual Reality Reminiscence Reduces Anxiety in the Oldest-Old Without Causing Serious Side Effects: A Single-Center, Pilot, and Randomized Crossover Study.

Background: Dementia is one the major problems of aging societies, and, novel and effective non-drug therapies are required as interventions in the oldest-old to prevent cognitive decline. Objective: This study aims to examine the efficacy and safety of reminiscence using immersive virtual reality (iVR reminiscence) focusing on anxiety that often appears with cognitive decline. The secondary objective is to reveal the preference for VR image types for reminiscence: live-action (LA) or computer graphics (CG). Methods: This was a pilot, open-label, and randomized crossover study which was conducted on January 2020 at a single nursing home. The subjects were randomly divided into two groups (A or B) in equal numbers, and they alternately viewed two types of VR images (LA and CG) themed on the mid- to late Showa era (A.D. 1955-1980) in Japan. In group A, the CG images were viewed first, and then the LA images were viewed (CG→ LA). In group B, the images were viewed in the opposite order (LA→ CG). Before VR viewing, subjects responded to Mini-Mental State Examination (MMSE) Japanese version and State-Trait Anxiety Inventory (STAI) Japanese version. After viewing the first and second VR, subjects responded to STAI and the numerical rating scale (NRS) for satisfaction and side effects (nausea, dizziness, headache, and tiredness). Results: Ten subjects participated in this study. The values of analyses are presented in the mean (SD). The age was 87.1 years (4.2), and the MMSE was 28.5 (1.8). The total STAI score before VR viewing was 36.1 (7.2), but it significantly decreased to 26.8 (4.9) after the first VR viewing (P = 0.0010), and further decreased to 23.4 (2.8) after the second VR viewing (P < 0.001). The NRS score for satisfaction tended to be higher after viewing LA in group A (CG→ LA) (CG vs. LA; 7.0 (2.3) vs. 8.6 (1.5), P = 0.0993), while in group B (LA→ CG), the score after CG was slightly lower than that after LA. There were no serious side effects. Conclusions: This study suggests that iVR reminiscence can reduce anxiety in the oldest-old without causing serious side effects. Furthermore, the impacts might be better with LA images.

[Clinicopathological Evaluation of Preoperative Chemotherapy Containing S-1 as a Treatment for Patients with Oral Squamous Cell Carcinoma during Waiting Time for Surgery].

BACKGROUND: In our department, patients with oral squamous cell carcinoma(OSCC)received preoperative chemotherapy containing S-1 to prevent the growth and dissemination of tumors during the waiting time before definitive surgery. We retrospectively evaluated the usefulness of this treatment. PATIENTS AND METHODS: One hundred and five patients comprising stages T1(26), T2(64), T3(7), and T4(8 cases)were enrolled in this study from July 2001 to June 2013. In principle, patients were administered S-1(80mg/m / 2/day, days 1-14)and followed by a drug holiday(days 15-21), continuing until 1 week before surgery. RESULTS: The median administration period was 14 days(256 days). Ninety-eight patients underwent definitive surgery, but 7 patients who revealed clinical CR underwent only biopsy and showed histological CR. The histological responses of all patients were CR(24), PR(22), and NC(59), and the response rate was 43.8%. Almost all adverse effects were Grade 1 or 2, except 1 case of neutropenia(Grade 3)and 1 case of urticaria(Grade 3). The 5-year overall survival rates were 86.7% in all cases, 95.3% in CR/PR cases, and 79.7% in NC cases. CONCLUSION: Preoperative S-1 administration during the waiting time was a safe and very effective method and was considered beneficial for patients with OSCC.

11ß-hydroxysteroid dehydrogenase type 1 is associated with antiretroviral therapy-induced increase in low-density lipoprotein cholesterol
.

OBJECTIVE: To investigate the association between 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity and antiretroviral therapy (ART)-induced increase in low-density lipoprotein cholesterol (LDL). MATERIALS AND METHODS: We enrolled 62 patients and used liquid chromatography-tandem mass spectrometry to measure 11ß-HSD1 activity, which was expressed as a ratio of the sum of urinary tetrahydrocortisol and allo-tetrahydrocortisol concentrations to urinary tetrahydrocortisone concentration. Patient data, including baseline laboratory values, were extracted from medical records for logistic regression analyses of factors associated with LDL increase during ART. The cutoff 11ß-HSD1 activity ratio associated with the LDL increase during ART was determined using receiver operator characteristic (ROC) curve analysis. RESULTS: The LDL level increased significantly from 88.8 mg/dL before ART to 106.7 mg/dL during ART (p = 0.04). Additionally, patients with increased LDL tended to have a higher 11ß-HSD1 activity ratio (1.59 vs. 1.21, p = 0.06) and longer duration of ART (13.9 vs. 10.2 months, p = 0.07) than patients with unchanged or decreased LDL. The cutoff 11ß-HSD1 activity ratio was 1.226. Results of the univariate logistic regression analysis suggested that 11ß-HSD1 activity ratio ≥ 1.226 was associated with LDL increase during ART (p = 0.011), with an odds ratio of 8.000. CONCLUSION: This study revealed the possible association between 11ß-HSD1 activity and ART-induced LDL increase. The findings of this study suggest that 11ß-HSD1 could be a useful drug target for the treatment of ART-induced hyperlipidemia.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan.

AIM: To investigate thrombotic microangiopathy (TMA) in liver transplantion, because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS: A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated, and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS: These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered, the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells, the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD, the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD, such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies, must be decided according to each case. CONCLUSION: The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Progressive familial intrahepatic cholestasis: a single-center experience of living-donor liver transplantation during two decades in Japan.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) results in liver cirrhosis. Therefore, some PFIC patients require liver transplantation (LT). Although three types of PFIC have been identified, their etiologies include unknown mechanisms. PATIENTS: A total of 717 recipients who underwent living-donor LT (LDLT) at <20 yr old were enrolled in this study. Among these recipients, 14 PFIC recipients comprising 11 PFIC type 1 (PFIC1) and three PFIC type 2 (PFIC2) were evaluated. RESULTS: Three of 11 PFIC1 recipients died, while all three PFIC2 recipients survived. Eight of 11 PFIC1 recipients showed steatosis after LDLT. Among the eight steatosis-positive PFIC1 recipients, seven showed severe steatosis and seven were complicated with steatohepatitis. Nine of 11 PFIC1 recipients showed fibrosis after LDLT, and eight of the nine fibrosis-positive PFIC1 recipients showed severe fibrosis. In contrast to the PFIC1 recipients, the PFIC2 recipients did not show any steatosis or fibrosis after LDLT. CONCLUSIONS: The clinical courses and outcomes of PFIC1 recipients after LDLT are still not sufficient owing to steatosis/fibrosis, unlike the case for PFIC2 recipients. As PFIC1 patients will require LT during the long-term progression of the disease, further strategy improvements are required for PFIC1 patients.

Liver transplantation for congenital biliary dilatation: a single-center experience.

BACKGROUND: Congenital biliary dilatation is a rare disease. Although the possibility of refractory cholangitis and/or the frequency of malignant tumors legitimize hepatobiliary surgery, repeated cholangitis and biliary obstruction result in secondary liver cirrhosis even after polysurgery. There are no definitive guidelines on liver transplantation for congenital biliary dilatation. PATIENTS: A total of 1,101 liver transplantation recipients were enrolled in this study. Eleven patients with congenital biliary dilatation including 5 patients with Caroli's disease were retrospectively analyzed in detail. RESULTS: Nine of 11 patients underwent initial operations before liver transplantation while 2 patients with Caroli's disease received liver transplantation as initial surgery, with good outcomes. All patients had intractable symptoms caused by liver cirrhosis, and growth delay was considerable in patients aged <20 years. Histopathological analysis of the native liver revealed hepatic fibrosis (≥F2). One patient with ABO incompatibility died. One patient with Caroli's disease accompanied with intrahepatic carcinoma survives 11.8 years after liver transplantation without any recurrences. CONCLUSIONS: Patients with congenital biliary dilatation with refractory symptoms and complications secondary to liver failure are appropriate candidates for liver transplantation. We suggest that liver transplantation is an effective therapeutic option for patients with congenital biliary dilatation with due consideration to many accompanying factors, such as clinical course, growth delay, image findings and histopathological analysis.

Facile synthesis of 1,1-difluoroallenes via the difluorovinylidenation of aldehydes and ketones.

2-Bromo-3,3-difluoroallylic acetates were readily prepared by the reaction of carbonyl compounds with 1-bromo-2,2-difluorovinyllithium, generated from 1,1-dibromo-2,2-difluoroethylene, followed by acetylation. On treatment with butyllithium, the bromoacetates underwent selective 1,2-elimination of lithium acetate to afford mono- and disubstituted 1,1-difluoroallenes in high yields.