Feasibility, Tolerability, and Effectiveness of Transbronchial Interventions in Elderly Patients With Malignant Central Airway Obstruction: A Retrospective Single-institution Study.

BACKGROUND: In elderly patients with malignant central airway obstruction (MCAO), the treating physicians often hesitate to undertake transbronchial interventions (TBIs) as a palliative procedure in view of the advanced age of the patients. METHODS: We conducted this retrospective study to evaluate the differences in the feasibility, tolerability, and effectiveness of TBIs between elderly (aged 75 years old or above; elderly group; n=27) and nonelderly (aged below 75 years old; nonelderly group; n=50) patients with MCAO. The primary endpoint was the incidence of complications during (within 24 hours) and after (>24 hours) TBIs. RESULTS: The mean age of the patients was 81 years in the elderly group and 61 years in the nonelderly group. The complications encountered during/after TBI included endobronchial bleeding or hypoxemia requiring intubation occurring during the TBIs, and bacterial pneumonia, airway reocclusion, and stent migration occurring after the TBIs, although there was no difference in the frequency of complications during/after the TBIs between the elderly group and nonelderly group (26% vs. 30%, P =0.706). There was no difference in the percentage of patients in whom successful airway recanalization was achieved by TBI (93% vs. 80%, P =0.197), the percentage of patients who showed symptomatic improvement after the TBIs (67% vs. 76%, P =0.380) and the OS after the TBIs (6.1 vs. 7.3 months, P =0.704) between the 2 groups. CONCLUSION: TBIs can be undertaken without hesitation as a palliative procedure in elderly patients with MCAO.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Phylogeography of the temperate grassland plant Tephroseris kirilowii (Asteraceae) inferred from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq) data.

A group of temperate grassland plant species termed the "Mansen elements" occurs in Japan and is widely distributed in the grasslands of continental East Asia. It has been hypothesized that these species are continental grassland relicts in Japan that stretch back to a colder age, but their migration history has not been elucidated. To assess the migration history of the Mansen elements, we performed phylogeographic analyses of Tephroseris kirilowii, a member of this group, using single-nucleotide polymorphisms (SNPs) obtained from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq). It was estimated that the Japanese populations of T. kirilowii were divided from those of continental East Asia at 25.2 thousand years ago (ka) with 95% highest probability density interval (HPD) of 15.3-40.0 ka and that Japanese clades first diverged at 20.2 ka with 95% HPD of 10.4-30.1 ka. As the climatically suitable range during the last glacial maximum (LGM) estimated using ecological niche modeling (ENM) was limited in Japan and there was a slight genetic differentiation among Japanese populations, a post-glacial expansion of T. kirilowii in the Japanese Archipelago was indicated.

Overall Survival of Small-cell Lung Cancer Patients With Malignant Central Airway Obstruction Who Received Chemotherapy Without Undergoing Transbronchial Interventions: A Single-institution Retrospective Study.

BACKGROUND/AIM: This study aimed to determine whether the prognosis of small-cell lung cancer (SCLC) patients with malignant central airway obstruction (MCAO) who receive chemotherapy without undergoing transbronchial intervention (TBI) is not inferior to that of SCLC patients without MCAO. PATIENTS AND METHODS: We compared overall survival (OS) from the time of SCLC diagnosis between stage III or IV SCLC patients with MCAO (MCAO group, n=22) and those without MCAO (non-MCAO group, n=88). MCAO is generally defined as >50% obstruction of the trachea or mainstem bronchi. RESULTS: The median interval from the time of SCLC diagnosis until the initiation of anticancer therapy and the median number of chemotherapy regimens were 6 days and 2 regimens, respectively, in the MCAO group and 15 days and 2 regimens in the non-MCAO group. During the median follow-up period of 11.7 months after SCLC diagnosis, 95% of the patients in the MCAO group and 85% of the patients in the non-MCAO group died. No difference in the median OS (11.9 months vs. 12.4 months, p=0.455) was seen between the MCAO group and the non-MCAO group. A multivariate analysis showed that the presence of MCAO was not associated with an increased risk of death in SCLC patients who received chemotherapy (p=0.664). CONCLUSION: The prognosis of SCLC patients with MCAO who receive chemotherapy without undergoing TBI is not inferior to that of SCLC patients without MCAO.

Prognosis of stage I non-small cell lung cancer patients aged ≥ 80 years who were considered medically operable but received best supportive care alone.

INTRODUCTION: Some elderly stage I non-small cell lung cancer (NSCLC) patients may refuse both stereotactic body radiotherapy (SBRT) and surgery and may instead desire best supportive care (BSC) alone, despite having a medically operable condition. METHODS: We retrospectively evaluated the differences in the 3-year overall survival (3-year OS) rates among elderly stage I NSCLC patients aged ≥ 80 years who received surgery (OP group, n = 39), SBRT (RT group, n = 32) or BSC alone (BSC group, n = 28), stratifying the later groups according to those who were medically inoperable (MI subgroup) and those who were considered medically operable but refused surgery (MO subgroup). RESULTS: During a median 39.1-month follow-up period, 44 patients died. The 3-year OS rates were longer and higher in the MI-RT subgroup and the OP group than in the MI-BSC subgroup (67%, 89%, and 22%, respectively; p = 0.001). No differences in the 3-year OS rates were seen among the MO-RT subgroup, the MO-BSC subgroup, and the OP group (75%, 70%, and 89%, respectively; p = 0.164). However, a multivariate analysis identified a performance status (PS) score of 1-2 or a Charlson comorbidity index (CCI) score of ≥2, as well as stage IB disease and BSC, as independently increasing the risk of death. CONCLUSIONS: Elderly stage I NSCLC patients who were medically operable but who refused surgery and desire BSC alone should be encouraged to undergo SBRT unless they have a good PS and are otherwise in healthy condition.

Difference in the Overall Survival Between Malignant Central Airway Obstruction Patients Treated by Transbronchial Microwave Ablation and Stent Placement: A Single-institution Retrospective Study.

BACKGROUND/AIM: Transbronchial microwave ablation (MWA) can be performed safely in patients with malignant central airway obstruction (MCAO), under moderate sedation and a high fraction of inspired oxygen. PATIENTS AND METHODS: We retrospectively evaluated the difference in the overall survival (OS) after transbronchial interventions (TBIs) between MCAO patients with endoluminal or mixed-type obstruction who were treated by MWA (MWA group, n=34) and those with extraluminal obstruction who were treated by stent placement (STP) (STP group, n=27). RESULTS: The OS was longer in the MWA group than in the STP group (10.2 months vs. 4.5 months, p=0.001). A significant difference in the OS between the two groups was observed in the patients who received post-TBI anticancer therapy (27.2 months vs. 6.0 months, p=0.002). The OS tended to be longer in the MWA group than in the STP group, among the patients who received best supportive care alone (3.8 months vs. 1.8 months, p=0.068). Nine patients (26%) of the MWA group underwent additional MWA when tumor regrowth into the airway lumen was noted (median of TBI sessions, 3). Multivariate analysis identified the adoption of MWA as the initial treatment procedure to be independently associated with a reduced risk of death in patients with MCAO (hazard ratio=0.473, p=0.031). CONCLUSION: Adoption of MWA as the initial treatment procedure is beneficial in MCAO patients with endoluminal or mixed-type obstruction, regardless of whether patients receive post-TBI anticancer therapy or not.

Molecular phylogeny and taxonomy of the Hydrangeaserrata complex (Hydrangeaceae) in western Japan, including a new subspecies of H.acuminata from Yakushima.

According to the contemporary classification of Hydrangea native to Japan, H.serrata is a polymorphic species including six varieties. We discovered a plant identified as H.serrata, but morphologically distinct from previously known varieties, in Yakushima island where approximately 50 endemic species are known. To determine the relationship of this plant with previously known varieties, we examined morphology and constructed a highly resolved phylogeny of H.serrata and its relatives using three chloroplast genomic regions, rbcL, trnL intron, psbA-trnH, and two nuclear genomic regions, ITS1 and ITS2, and Multiplex ISSR genotyping by sequencing (MIG-seq). Based on these morphological and phylogenetic observations, we describe Hydrangeaacuminatasubsp.yakushimensissubsp. nov. as a newly discovered lineage in Yakushima, Japan and propose Hydrangeaminamitanii stat. nov. and Hydrangeaacuminatasubsp.australisstat. nov. which were previously treated as varieties of H.serrata.

 Hydrangeamarunoi (Hydrangeaceae), a new species from Osumi Peninsula, southern Japan.

Hydrangeamarunoi Tagane & S. Fujii, from the Kimotsuki Mountains in the Ohsumi Peninsula, southern Japan, is described and illustrated. It is morphologically similar to H.alternifolia in having three-petaloid calyx lobes in marginal flowers, but is distinguished by the larger stamen number, and longer styles and seeds. Multiplex ISSR genotyping by sequencing (MIG-seq) demonstrated that the new species is monophyletic and closely related to H.amamiohsimensis and H.moellendorffii rather than H.alternifolia.

Efficacy and safety of transbronchial microwave ablation therapy under moderate sedation in malignant central airway obstruction patients with respiratory failure: a single-institution retrospective study.

BACKGROUND: The safety and efficacy of transbronchial microwave ablation (TMA) therapy in patients with malignant central airway obstruction (CAO) with respiratory failure remains unclear. METHODS: A total of 38 patients with advanced non-small cell lung cancer (NSCLC) or lung metastases with malignant endoluminal obstruction received TMA therapy under moderate sedation and high fractions of inspired oxygen (FiO2). The success rate of airway patency restoration, complication rate, and overall survival time (OS) from the initiation of TMA therapy were compared in the following two groups of patients with malignant CAO patients: the group with respiratory failure (PaO2/FiO2 ≤ 300) (RF group, n = 10) and the group without respiratory failure (PaO2/FiO2 > 300) (non-RF group, n = 28) at the time of the TMA therapy. RESULTS: Both the RF group and non-RF group received a median of two sessions of TMA. There was no significant difference in the percentage of patients who showed restored airway patency after the first session of TMA (90% vs. 96%), in the complication rate of TMA therapy (10% vs. 11%), or in the OS (7.1 months vs. 9.1 months) between the RF group and the non-RF group. Multivariate analysis identified no significant association between TMA therapy and the risk of death in malignant CAO patients with respiratory failure (p = 0.196). CONCLUSION: TMA therapy under moderate sedation was well tolerated and effective in patients with malignant CAO, including those with respiratory failure.

Phylogeographic and demographic modeling analyses of the multiple origins of the rheophytic goldenrod Solidago yokusaiana Makino.

Understanding adaptation mechanisms is important in evolutionary biology. Parallel adaptation provides good opportunities to investigate adaptive evolution. To confirm parallel adaptation, it is effective to examine whether the phenotypic similarity has one or multiple origins and to use demographic modeling to consider the gene flow between ecotypes. Solidago yokusaiana is a rheophyte endemic to the Japanese Archipelago that diverged from Solidago virgaurea. This study examined the parallel origins of S. yokusaiana by distinguishing between multiple and single origins and subsequent gene flow. The haplotypes of noncoding chloroplast DNA and genotypes at 14 nuclear simple sequence repeat (nSSR) loci and single-nucleotide polymorphisms (SNPs) revealed by double-digest restriction-associated DNA sequencing (ddRADseq) were used for phylogeographic analysis; the SNPs were also used to model population demographics. Some chloroplast haplotypes were common to S. yokusaiana and its ancestor S. virgaurea. Also, the population genetic structures revealed by nSSR and SNPs did not correspond to the taxonomic species. The demographic modeling supported the multiple origins of S. yokusaiana in at least four districts and rejected a single origin with ongoing gene flow between the two species, implying that S. yokusaiana independently and repeatedly adapted to frequently flooding riversides.

Overall survival of super-elderly (85 years or older) advanced non-small cell lung cancer patients with active epidermal growth factor receptor mutations receiving first-line gefitinib therapy: a single-institute retrospective study.

BACKGROUND: The survival benefit of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in super-elderly patients with advanced non-small cell lung cancer (NSCLC) harboring active EGFR mutations remains unclear. METHODS: We conducted a retrospective evaluation of the difference in the overall survival (OS) among super-elderly (aged ≥ 85 years) NSCLC patients who had received best supportive care alone (BSC group, n = 36), cytotoxic chemotherapy (CT group, n = 11) or EGFR-TKI therapy (TKI group, n = 22). RESULTS: The median age of the patients was 88 years. Among the 35 super-elderly NSCLC patients with an performance status (PS) score of 0-2, 11of 18 EGFR wild-type patients received cytotoxic chemotherapy and 15 of 17 EGFR-mutant patients received EGFR-TKI therapy with gefitinib (n = 13) or osimertinib (n = 2). The OS tended to be longer in the TKI group than in the CT or BSC group (16.9 months vs. 7.2 months or 9.8 months, p = 0.059). Among the 34 super-elderly NSCLC patients with a PS score of 3-4, 7 with EGFR-mutant received gefitinib therapy and the remaining 27 received BSC alone. The OS tended to be longer in the TKI group than in the BSC group (4.6 months vs. 2.3 months, p = 0.060). Multivariate analysis identified a good PS before the start of first-line therapy and presence of active EGFR mutations reduced a risk of death. CONCLUSIONS: Gefitinib appears to be useful as a salvage therapy in super-elderly NSCLC patients with active EGFR mutation, regardless of their PS.

Impact of cancer therapy on post-treatment ejaculation disorder and sexual life in testicular cancer survivors.

OBJECTIVE: To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS: A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS: Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001). CONCLUSION: Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life.

Trends in Age and Histology of Testicular Cancer from 1980-2019: A Single-Center Study.

Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.

Chemotherapy should be performed in epidermal growth factor receptor mutation-positive lung adenocarcinoma patients who had progressive disease to the first epidermal growth factor receptor-tyrosine kinase inhibitor.

After the failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, some non-small cell lung cancer patients desire to receive switching with another EGFR-TKI (TKI-switching), although cytotoxic chemotherapy has been recommended as second-line therapy. It is unclear who should not receive TKI-switching in these patients. We retrospectively evaluated overall survival (OS) from the initiation of first EGFR-TKI (first-TKI) therapy in advanced lung adenocarcinoma patients with active EGFR mutations (deletion of exon 19 or L858R in exon 21) who received TKI-switching according to the best response of the first-TKI. There was no difference in the OS between patients receiving TKI-switching (n = 35) and patients receiving additional chemotherapy between the first-TKI and second-TKI therapy (n =10) (P = 0.614). Among patients receiving TKI-switching, the OS in cases with progressive disease to the first-TKI (n = 9) was shorter than that in cases with disease control to the first-TKI (n = 26) (12.7 months vs. 49.4 months, P < 0.001). Five of the nine progressive disease cases who received TKI-switching missed an opportunity to receive chemotherapy. Their OS tended to be shorter than that in patients who received chemotherapy during the whole period of anticancer therapy (12.2 months vs. 20.3 months, P = 0.060). The multivariate analysis showed that disease control to the first-TKI therapy (P = 0.005) or the presence of chemotherapy (P = 0.087) decreased the risk of mortality. Chemotherapy should be performed in patients with progressive disease to the first-TKI.

Timing of resumption of immune checkpoint inhibitor therapy after successful control of immune-related adverse events in seven advanced non-small cell lung cancer patients.

Among advanced non-small cell lung cancer (NSCLC) patients in whom grade 2/3 immune-related adverse events (irAEs) that had developed during the initial immune checkpoint inhibitor (ICI) therapy had been successfully controlled, we experienced three patients in whom ICI therapy was resumed at the diagnosis of progressive disease (PD group, n = 3) and four patients in whom it was resumed immediately after successful control of irAEs (non-PD group, n = 4). The tumor response rate, disease control rate to the resumed ICI and progression-free survival from the resumption of ICI therapy were 0%, 0% and 2 months in the PD group and 25%, 75% and 4.8 months in the non-PD group. In advanced NSCLC patients in whom resumption of discontinued ICI therapy was planned, the ICI therapy should be resumed immediately after successful control of irAEs, rather than at the diagnosis of PD.

Additional bevacizumab in EGFR-mutant lung adenocarcinoma patients who had oligo-progression after the failure of EGFR-TKI: A single-institute retrospective study.

INTRODUCTION: In EGFR-mutant NSCLC patients with oligo-progression disease (oligo-PD) after the EGFR-TKI failure, additional local ablative therapy (LAT) including stereotactic ablative radiotherapy reportedly extends the duration of the current EGFR-TKI and prolongs survival times. In clinical practice, however, all the patients cannot receive LAT for oligo-PD. METHODS: We retrospectively evaluated the efficacy and tolerability of additional bevacizumab as an alternative to LAT for oligo-PD after the EGFR-TKI failure in previously treated lung adenocarcinoma patients (median number of previous therapies, 2 regimens). Oligo-PD was defined as a situation in which disease progression has occurred in less than 5 anatomical sites after EGFR-TKI that has achieved at least stable disease. RESULTS: During a median 29.6-month follow-up period from the initiation of EGFR-TKI, 9 patients developed oligo-PD. One patient underwent LAT, but other 8 patients did not because of a few micro-metastatic lesions (n = 2), meningitis (n = 1), no indication of pleurodesis (n = 1), patient refusal (n = 2) or oligo-PD in the LAT treated sites (n = 3). Additional bevacizumab with continuation of the current EGFR-TKI had a disease control rate of 100% and a median time of progression-free survival from additional bevacizumab until another PD was 8.8 months. The reason for the discontinuation was because of another PD (n = 6) or treatment-related adverse events (n = 3). Four patients received sequential therapy and overall survival from additional bevacizumab was 10.1 months. CONCLUSIONS: Additional bevacizumab could be useful for EGFR-mutant adenocarcinoma patients with oligo-PD after the EGFR-TKI failure.

Effects of a Novel Piezo Actuator-driven Pulsed Water Jet System on Residual Kidney After Partial Nephrectomy in a Rat Model.

OBJECTIVE: To evaluate renal damage after off-clamp partial nephrectomy (PN) using a novel surgical device, piezo actuator-driven pulsed water jet (ADPJ) system. METHODS: Sprague-Dawley rats were divided into 4 groups and subjected to sham operation, off-clamp PN by the piezo ADPJ system, radio knife, and soft coagulation, which have been used as thermal coagulation devices. Urine and blood samples were collected, and residual kidneys were harvested at 1, 7, 14, 30, and 90 days after PN. Serum blood urea nitrogen, creatinine, and urinary and serum kidney injury molecule-1 KIM-1 levels were measured. Morphological features and the extent of renal ischemia of resection surfaces were evaluated by hematoxylin-eosin staining and immunostaining using antibodies to 1-methyladenosine, respectively. In addition, the expression levels of KIM-1 mRNA extracted from each resection surface were analyzed by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Serum blood urea nitrogen and creatinine were significantly lower with the piezo ADPJ system than with soft coagulation. Urinary and serum KIM-1 levels were also significantly decreased with the ADPJ. The extent of 1-methyladenosine immunostaining was significantly less with the ADPJ than with thermal coagulation devices. The expression levels of KIM-1 mRNA were also lower in the ADPJ system group. CONCLUSION: The piezo ADPJ system might attenuate renal damage after off-clamp PN.

Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model.

BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

Toxicity and Efficacy of Sequential Chemotherapy in Patients with p-stage I Non-small Cell Lung Cancer that Recurring during Postoperative Tegafur-Uracil Adjuvant Chemotherapy.

It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.

Re-administration of Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer Who Recovered from Chemotherapy-induced Interstitial Lung Disease.

We reported that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor re-administration (TKI-R) might be salvage therapy in patients with advanced non-small cell lung cancer after recovery from EGFR-TKI-induced interstitial lung disease (ILD). Here we retrospectively evaluated whether chemotherapy re-administration (CT-R) was effective in patients after chemotherapy-induced ILD. After providing their informed consent due to the risk of severe ILD, five patients received CT-R and six received TKI-R with oral administration of 0.5 mg/kg prednisolone. The overall survival (OS) from the occurrence of drug-induced ILD was shorter in CT-R cases than that in TKI-R cases (7.3 months vs. 25.4 months, p=0.003). The median duration of OS, however, was 7.3 months in cases with CT-R and 1.9 months in cases without CT-R. Multivariate analysis showed that CT-R as well as TKI-R tended to reduce the risk of mortality. CT-R might be salvage therapy in such patients, although the benefit of CT-R was smaller than that of TKI-R.