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Purpose: The aim of this study was to examine the clinical utility of tumor-infiltrating lymphocytes (TILs) evaluated by "average" and "hot-spot" methods in breast cancer patients., Methods: We examined 367 breast cancer patients without neoadjuvant chemotherapy (NAC) by average and hot-spot methods to determine the consistency of TIL scores between biopsy and surgical specimens. TIL scores before NAC were also compared with the pathological complete response (pCR) rate and clinical outcomes in 144 breast cancer patients that received NAC. TIL scores evaluated by the two methods were predicted from clinicopathological data using random forest regression., Results: Surgical specimens showed higher TIL scores than biopsy specimens using the hot-spot method (p < 0.001), while biopsy and surgical specimens showed similar TIL scores using the average method. There was a linear relationship between the pCR rate and TIL scores determined using hot-spot (p < 0.001) and average methods (p = 0.001). Patients without pCR and low TILs by the average method had significantly worse overall survival compared to other patients (p = 0.02). The root mean squared errors of the predicted TIL score for the test set were 19.662 (hot-spot) and 10.955 (average)., Conclusion: The average method may have an advantage for breast cancer patients receiving NAC, since the TIL score using this method is more consistent between biopsy and surgical specimens, and it associates better with clinical outcomes. Our exploratory study showed that machine learning from clinicopathological data may better predict TIL scores assessed by the average, rather than hot-spot, method., Competing Interests: Declarations. Conflicts of interest: M Nagahashi received honoraria from Chugai, AstraZeneca, Eli Lilly, Pfizer, Novartis, Taiho, Daiichi Sankyo, Esai, Kyowa-Kirin, and Denka. Y Miyoshi received research funding and honoraria from Esai, Chugai, AstraZeneca, Eli Lilly, Pfizer, MSD, Kyowa-Kirin, Daiichi-Sankyo, and Taiho. E Ishikawa, T Nagai, H Kanaoka, A Oshiro, Y Togashi, A Hattori, J Tsuchida, T Higuchi, A Nishimukai, K Murase, Y Takatsuka, T Kihara, Y Ling, S Okuda, S Hirota have no conflicts of interest., (© 2025. The Author(s).)

Purpose: The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR), at the end of treatment (EOT) with CDK4/6 inhibitors abemaciclib and palbociclib in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer., Methods: We included 67 patients treated with fulvestrant plus abemaciclib or palbociclib. Overall survival (OS) since the EOT with CDK/4/6 inhibitors was compared in relation to the levels of ALC and NLR. The cut-off values of ALC and NLR were set at 1000/μL and 3, respectively., Results: Patients with a high ALC at EOT showed significantly longer OS than those with a low ALC (p = 0.0358). Moreover, patients with a low NLR at EOT showed significantly longer OS than those with a high NLR at EOT (p = 0.0044). Looking at the changes of ALC and NLR between baseline and the EOT, patients with a high ALC both at baseline and at the EOT showed significantly longer OS than others (p = 0.0201). Similarly, patients with a low NLR both at baseline and at the EOT showed significantly longer OS after EOT than others (p = 0.0136). Multivariable analysis revealed that the NLR at EOT (low vs. high) and changes in NLR (low at baseline to low at EOT vs. others) were significant and independent prognostic factors for OS after EOT (p = 0.0337, p = 0.0039, respectively)., Conclusion: NLR at EOT with CDK4/6 inhibitors is a significant and independent prognostic marker for patients with ER-positive HER2-negative advanced breast cancer., Competing Interests: Declarations. Conflict of interest: M Nagahashi received honoraria from Chugai, AstraZeneca, Eli Lilly, Pfizer, Novartis, Taiho, Daiichi Sankyo, Esai, Kyowa-Kirin, and Denka. Y Miyoshi received research funding and honoraria from Esai, Chugai, AstraZeneca, Eli Lilly, Pfizer, MSD, Kyowa-Kirin, Daiichi-Sankyo, and Taiho. A Mitsuyoshi, H Kanaoka, A Oshiro, Y Togashi, A Hattori, T Higuchi, A Nishimukai, K Murase, Y Takatsuka have no conflict of interest., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

A 49-year-old woman who had surgery for left breast cancer and subsequently underwent a two-stage deep inferior epigastric perforator(DIEP)flap reconstruction. One month postoperatively, she became aware of abdominal distention and visited a local hospital. CT scan revealed subcutaneous fluid accumulation with capsular formation in the lower abdomen. Imaging findings and physical examination showed no abdominal wall scar hernia. After multiple puncture aspirations, fluid accumulation was observed again, and the possibility of a chronic expanding hematoma was considered. Later, hematoma removal, including the capsules, was performed; pathological findings showed no evidence of malignancy. No fluid retention was observed postoperatively. In cases where imaging evaluation reveals hematoma formation with capsules, hematoma removal, including the capsules, should be performed to avert the possibility of a chronic expanding hematoma.

Background: Tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients. However, the TIL level can be determined at a few facilities. By contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily and objectively determined from the results of full blood counts. We conducted a retrospective study to investigate whether TILs, NLR, and PLR predict NAC efficacy and whether NLR and PLR could be surrogate markers for TILs in TNBC., Methods: Of the 266 patients diagnosed with TNBC between 2013 and 2019, 66 who underwent radical surgery after sequential administration of anthracycline and taxane as NAC were included in the study. TILs, NLR, and PLR were evaluated as predictors of pathologic complete response (pCR) using cutoff values determined from receiver operating characteristic curves., Results: The cutoff values of TILs, NLR, and PLR were 20%, 2.6, and 180, respectively. High TIL level was associated with low NLR (P = 0.01) and low PLR (P = 0.01). High TIL level (odds ratio [OR] 4.28 [95% CI 1.40-13.1]; P = 0.01), low NLR (OR 5.51 [95% CI 1.60-18.9]; P = 0.01), and low PLR (OR 3.29 [95% CI 1.13-9.57]; P = 0.03) were associated with pCR. Low NLR predicted pCR independently (OR 6.59 [95% CI 1.45-30.0]; P = 0.01)., Conclusions: TILs, NLR, and PLR predicted NAC efficacy against TNBC. TIL level was associated with NLR and PLR. NLR was an independent predictive factor and may be a useful surrogate marker for TILs when predicting pCR., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background/aim: The efficacy of endocrine therapy combined with abemaciclib for hormone receptor-positive, HER2-negative metastatic breast cancer has been established through pivotal clinical trials. However, abemaciclib-induced liver injury (AILI) can be a cause for dose reduction or discontinuation. Therefore, it is critical to understand the risk factors for AILI., Patients and Methods: This retrospective study analyzed data from patients who had received abemaciclib combined with endocrine therapy for metastatic breast cancer as first- or second-line therapy at our hospital between December 2018 and October 2021. Relevant data were extracted from their medical records. Logistic regression analysis was performed to identify characteristics associated with AILI., Results: Of the 52 eligible patients, 12 (23%) received an aromatase inhibitor (AI), and 40 (77%) received fulvestrant, concomitantly with abemaciclib. Fifteen (29%) of the patients developed liver injury after starting abemaciclib. Univariate analysis revealed the following risk factors for AILI: age ≥65 years (p=0.047), fatty liver disease (p=0.047), and concomitant use of an AI (p=0.002). Concomitant use of an AI was identified by multivariate analysis as an independent risk factor for AILI [odds ratio (OR)=10.23, 95% confidence interval (CI)=2.02-51.91, p=0.005]., Conclusion: Concomitant use of an AI could be the most significant factor associated with increased risk of AILI. Future research on the mechanism by which the use of an AI plus abemaciclib can cause liver injury, and prospective studies to validate our findings regarding AILI risk factors, are warranted., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The molecular chaperones HdeA and HdeB of the Escherichia coli (E. coli) periplasm protect client proteins from acid denaturation through a unique mechanism that utilizes their acid denatured states to bind clients. We previously demonstrated that the active, acid-denatured form of HdeA is also prone to forming inactive, amyloid fibril-like aggregates in a pH-dependent, reversible manner. In this study, we report that HdeB also displays a similar tendency to form fibrils at low pH. HdeB fibrils were observed at pH < 3 in the presence of NaCl. Similar to HdeA, HdeB fibrils could be resolubilized by a simple shift to neutral pH. In the case of HdeB, however, we found that after extended incubation at low pH, HdeB fibrils were converted into a form that could not resolubilize at pH 7. Fresh fibrils seeded from these “transformed” fibrils were also incapable of resolubilizing at pH 7, suggesting that the transition from reversible to irreversible fibrils involved a specific conformational change that was transmissible through fibril seeds. Analyses of fibril secondary structure indicated that HdeB fibrils retained significant alpha helical content regardless of the conditions under which fibrils were formed. Fibrils that were formed from HdeB that had been treated to remove its intrinsic disulfide bond also were incapable of resolubilizing at pH 7, suggesting that certain residual structures that are retained in acid-denatured HdeB are important for this protein to recover its soluble state from the fibril form.

Background/aim: The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer treated with the CDK4/6 inhibitors, abemaciclib and palbociclib., Patients and Methods: A total of 83 patients treated with fulvestrant plus abemaciclib or palbociclib were included in this study. Progression-free survival (PFS) and overall survival (OS) were compared in relation to baseline levels of ALC, NLR, PLR and CRP., Results: The cut-off values of ALC, NLR, PLR, and CRP for PFS were determined from the receiver operating characteristic curve using the Youden index for area under the curve and set at 1,212/μl, 1.964, 170 and 0.220 mg/dl, respectively. In the abemaciclib-treated group, ALC-high patients showed significantly better PFS than ALC-low patients (p=0.0151) and multivariate analysis revealed that ALC was an independent prognostic factor for PFS (p=0.0085). In the palbociclib-treated group, there was no significant relationship between any peripheral blood biomarkers and PFS. In both treatment groups, ALC-high patients showed significantly better OS than ALC-low patients (p=0.0169 and 0.0290, respectively). Multivariate analysis revealed ALC was an independent prognostic factor for OS in both abemaciclib- and palbociclib-treated groups (p=0.0112 and 0.0202, respectively)., Conclusion: ALC is an independent prognostic factor for estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer patients treated with the CDK4/6 inhibitors abemaciclib and palbociclib., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Endocrine therapy (ET) with or without CDK4/6 inhibitors is the primary treatment choice for patients with estrogen receptor (ER)-positive and HER2-negative subtype of metastatic breast cancer (MBC). We examined the metabolic parameters identified using 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in terms of sensitivity, since no predictive factors exist., Patients and Methods: We included 136 patients with MBC treated with ET alone (n=107) or combined with CDK4/6 inhibitor (n=29) and examined using FDG-PET before treatment began. The highest maximum value of the standard uptake value (SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated., Results: Progression-free survival (PFS) was significantly longer in patients with low levels of MTV, TLG, and SUVmax than those with higher levels (median PFS 49.5 vs. 20.7 months, p=0.001 for MTV, 49.5 vs. 20.7 months, p=0.0016 for TLG, 37.0 vs. 20.7 months, p=0.012 for SUVmax). Multivariable analysis revealed that TLG (hazard ratio=6.383, 95% confidence interval=1.167-34.913, p=0.033) was independently and significantly associated with PFS. The relationship between TLG levels and PFS was significant in patients treated with ET with (p=0.0054) and without (p=0.0188) CDK4/6 inhibitor., Conclusion: TLG at baseline was a significant predictor for sensitivity to ET alone or combined with CDK4/6 inhibitor. These data may be useful to identify patients that would benefit from ET., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pegfilgrastim (PEG) is a sustained-duration pegylated form of filgrastim, a granulocyte-colony stimulating factor agent that is widely used as prophylaxis against febrile neutropenia during chemotherapy. We report the case of a breast cancer patient who developed PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) and review the relevant literature., Case Presentation: A 48-year-old woman had undergone surgery for breast cancer and was receiving docetaxel and cyclophosphamide as adjuvant chemotherapy (docetaxel 75 mg/m 2 , cyclophosphamide 600 mg/m 2 ); on day 4 of treatment, PEG had been administered. On day 14, she was admitted to hospital with fever, general malaise, and neck pain, and her C-reactive protein level was found to be high (12.65 mg/dL). Although infection was initially suspected, antimicrobial treatment was ineffective and other laboratory test results were negative for this. Contrast-enhanced computed tomography on day 22 showed thickened vessel walls in the left subclavian artery, the origin of the common carotid artery, and the thoracoabdominal aorta. On day 26, magnetic resonance imaging of the head to investigate possible causes of headache showed signs consistent with SAH, and magnetic resonance angiography images showed irregularity in the basilar artery wall; the findings of both studies were considered to be due to PEG-induced vasculitis. Once treatment with prednisolone 40 mg/day had started, the wall thickening and irregularity improved., Conclusion: Although an uncommon adverse effect, vasculitis affecting vessels of various sizes may be caused by PEG. To the best of our knowledge, this report is the first to describe a case of G-CSF-induced vasculitis complicated by SAH. In cases of persistent high fever and elevated inflammatory response after PEG administration and in the absence of infection, clinicians should consider the possibility of drug-induced vasculitis., (© 2022. The Author(s).)

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.

Background: There is no established view of how gastric acid suppression affects the time for gastric emptying. Vonoprazan fumarate shows potent and durable gastric acid inhibitory effects, but its effects on gastric emptying have not been studied widely. We investigated the effects of vonoprazan fumarate on gastric emptying and measured serum gastrin and plasma ghrelin levels in healthy adults., Methods: Ten participants were administered 10 mg vonoprazan fumarate daily for 14 days, then 20 mg vonoprazan fumarate daily for 14 days. The gastric emptying breath test was performed and serum gastrin levels were measured at baseline and after each medication administration period. The protocol was then repeated, with the gastric emptying breath test and serum gastrin and plasma desacyl-ghrelin levels measured at baseline and the end of the medication trial., Results: Mean serum gastrin levels increased in a dose-dependent manner [baseline: 104.7 ± 50.4, after 10 mg protocol: 328 ± 123.8, after 20 mg protocol: 555 ± 378.8 (pg/mL, mean ± standard deviation), p = 0.0008]. There was a significant difference between the gastric emptying breath test Tmax at baseline and just after the 20 mg protocol (baseline: 45.5 ± 15.3, after 20 mg protocol: 60.5 ± 19.6 min, p = 0.0418). Plasma desacyl-ghrelin levels increased significantly just after the 20 mg protocol compared to those at baseline [baseline: 222.3 ± 106.4, after 20 mg protocol: 366.2 ± 178.6 (fmol/mL), p = 0.0008]., Conclusions: In healthy adults, 14 days of vonoprazan fumarate administration at 20 mg/day delayed gastric emptying., Trial Registration: This clinical trial was registered in the University hospital Medical Information Network Clinical Trial Registry (Trial No. UMIN000039199 and UMIN000042969)., (© 2021. Japanese Society of Gastroenterology.)

Background: Little is known about the efficacy of proton-pump inhibitor (PPI) therapy in the management of esophageal ulcers after endoscopic submucosal dissection (ESD). Therefore, the objective of this study was to investigate the efficacy of PPI in ulcer healing following ESD for superficial esophageal neoplasms, using a propensity score analytic approach., Methods: This retrospective cohort study was conducted at a single referral center. Between April 2005 and August 2015, 199 consecutive patients with superficial esophageal cancer and esophageal dysplasia underwent ESD. For patients with PPI administration, intravenous PPI therapy was commenced immediately after ESD, and oral PPI was administered daily from post-operative day 3, until ulcer healing was identified. We compared the remnant-ulcer rate at 4 weeks after esophageal ESD between the PPI administration and non-PPI groups, using propensity scores and the inverse probability of treatment weighting (IPTW) method., Results: After exclusions, a total of 88 patients were analyzed. The remnant-ulcer rate at 4 weeks after ESD was 25.5% (12/47) and 14.6% (6/41) in the PPI administration and non-PPI groups ( p  = 0.21). After adjusting for background factors using IPTW, the risk of a remnant ulcer in the PPI administration group was not decreased significantly compared with that in the non-PPI group [odds ratio (OR) = 2.42, 95% confidence interval (CI): 0.73-7.97, p  = 0.15]. Furthermore, PPI therapy did not decrease significantly the remnant-ulcer rate on logistic regression analysis after adjusting for the propensity score (OR = 2.40, 95% CI: 0.69-8.32, p  = 0.15)., Conclusion: PPI administration does not promote ulcer healing after ESD for superficial esophageal squamous cell carcinoma., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma.

Aims: Hormonal imbalances can affect a woman's physical and mental condition, impacting her daily life and productivity. A mobile application, "Karada-no-kimochi", predicts the menstrual cycle based on recorded data, and provides the information regarding menstruation. This study investigates the effectiveness of the application from health condition and labor productivity loss perspectives, and evaluates its cost-effectiveness for employed women in Japan., Materials and Methods: A randomized controlled trial (RCT) was performed to compare the use of the application and non-intervention in female workers (20-45 years) based on an online survey. A discrete-event model based on the RCT data, published literature, and claims data was used for the cost-effectiveness analysis., Results: The intervention and non-intervention groups comprised 612 and 914 women, respectively. In the intervention group, the incidences of depression (0.16%) and dysmenorrhea (0.33%) were significantly lower than those of the non-intervention group (0.77% and 1.31%, respectively) in the third month. While labor productivity and absenteeism varied, presenteeism showed almost no change across groups. The quality-adjusted life year in the intervention group was 6.84 (0.07 higher than that in the non-intervention group). By analyzing medical expenses and making assumptions regarding productivity, we estimated that the aggregate of medical expenses, productivity loss, and application fee for the intervention group could be lower than that of the non-intervention group by over JPY 130,000 (USD 1,170, as of December 2017) per individual., Limitations: The subjects included were willing or relatively willing to use the application. Because all outcomes were based on online surveys, the results depended on the objectivity and preciseness of the reports provided by users, and those with severe symptoms might not provide reports., Conclusions: The results suggest that using the application is cost-effective and might reduce the incidence of dysmenorrhea and depression.

The β-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of β-decay half-lives are observed at neutron-number N=97 for &#95;{58}Ce, &#95;{59}Pr, &#95;{60}Nd, and &#95;{62}Sm, and N=105 for &#95;{63}Eu, &#95;{64}Gd, &#95;{65}Tb, and &#95;{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.

To explore clinical protocols for the prevention of early-onset group B Streptococcus (EOGBS) disease of the newborn in Japan, we conducted a multicenter questionnaire survey. Of 32 regional centers participating in the Kyoto Neonatal Study Group, 28 provided usable data concerning prevention practices undertaken between 2000 and 2004. Twenty-three (82%) of the 28 hospitals implemented bacteriological screening to identify maternal GBS carriage, and all 23 hospitals administered intrapartum antibiotics to all screening-positive pregnant women. There were no institutes that used risk-based strategies. In the 23 hospitals, bacteriological screening was conducted mostly by lower vaginal swab alone (n = 18). Eighteen hospitals performed screening once during pregnancy, either before 34 weeks' gestation (n = 6) or between 35 and 37 weeks' gestation (n = 12). Oral antepartum antibiotics, when carriage was identified, were administered at 12 (52%) hospitals. Twenty institutes used penicillins for intrapartum prophylaxis. However, the loading dose for chemoprophylaxis ranged from 0.5 to 2 g, and the interval between repeat administrations ranged from 4 to 12 h. Although the results indicated that more than 80% of the hospitals surveyed had introduced some screening-based prevention practices, the timing of the bacteriological screening during the pregnancy, the number of screenings, and the screening sites, as well as the antibiotics used, and their dosage, varied widely. Because of these highly variable methods, the efficacy of the implementation of preventive practices could not be determined. This study is the first to have described preventive practices for EOGBS disease in Japan in the era of Centers for Disease Control and Prevention guidelines. In light of the above results, a larger study under a unifying protocol would be warranted.

We investigated the side effects of interferon (IFN) on the endocrine and respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%) patients with chronic hepatitis C who were treated with natural or recombinant interferon (IFN) developed thyroid disease while on treatment. Eight patients developed hyperthyroidism and 3 patients developed hypothyroidism. All 11 patients required definitive therapy, who became euthyroid after the therapy. Two patients received nIFN alpha and one patient received rIFN alpha 2b developed diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b, respectively, developed interstitial pneumonia 12 weeks and 24 weeks later, respectively. One patient showed positive reaction for RA test and LE factor and positive LE cell, and complained of fever, arthralgia and dry cough. These phenomenon disappeared after the cessation of IFN therapy.

A 41-year-old male patient of Budd-Chiari syndrome associated with membranous obstructions of the retrohepatic inferior vena cava and the left hepatic vein was reported. A radical operation was carried out. The retrohepatic inferior vena cava was reconstructed by a ringed EPTFE patch graft after endovenectomy with the aid of extracorporeal circulation for caval and portal bypasses utilizing cold hepatic perfusion. The patient has been doing well 18 months after the operation.

This study investigated the reversibility of sinusoidal capillarization in fibrotic rat liver induced by thioacetamide (TAA; 200 mg/kg body weight three times a week). Six weeks later, collagen fibers and hepatic lobular disarrangement were observed on light microscopy and basement membrane formation was noted in the space of Disse. Sinusoidal endothelial fenestrations (SEFs) were decreased in size and number (defenestration), and factor VIII-related antigen was observed in the cytoplasm. We also clarified the phenotypic reversibility of the sinusoidal endothelial cells. After 4 months following discontinuation of TAA exposure, the diameters and numbers of SEFs were increased. Six months later, the basement membrane in the space of Disse disappeared (as assessed by electron microscopy) and 12 months later, factor VIII-related antigen also disappeared. These results indicate that phenotypical changes in the sinusoidal endothelial cells and sinusoidal capillarization in hepatic fibrosis may be reversed.

The immunoelectron microscopic localization of actin in hepatocytes was studied in normal, common bile duct-ligated, and phalloidin treated rats. We used the low temperature embedding procedure with Lowicryl K4M and protein A-gold technique was applied to demonstrate the localization of actin. The tissues embedded in Lowicryl K4M at low temperature provided good preservation of ultrastructure and antigenicity of actin. In control rats bile canaliculi were clearly visualized and most of the gold particles were observed on the bile canalicular microvilli, at the pericanalicular ectoplasm, at the cell border, and on the sinusoidal microvilli. In common bile duct-ligated rats and phalloidin treated rats, pericanalicular ectoplasm was thickened and many gold particles were seen there.

The cytoskeletons of hepatocytes and biliary epithelial cells in bile duct ligated rate livers were investigated by transmission and scanning electron microscopy. The three dimensional organization of the intermediate filaments (IFs) of hepatocytes and biliary epithelial cells was clearly demonstrated by scanning electron microscopy. Cell borders and dilated bile canaliculi were well preserved after perfusion with detergent solution. A very dense filamentous network of IFs was seen throughout the cytoplasm, especially around the dilated bile canaliculi and at the cell borders. IFs in biliary epithelial cells were more numerous compared with hepatocytes. Morphometric analysis showed that the IFs of hepatocytes significantly (p greater than 0.001) increased in amount in bile duct ligated rats. The IFs of biliary epithelial cells showed no significant changes in bile duct ligated rats compared to controls. These results suggest that the increase in IFs in hepatocytes results from the adaptation of the hepatocytes to the stress imposed by bile duct ligation. It may be that the resulting intracanalicular pressure and back diffusion of bile induces a metaplastic change in hepatocytes so that they acquire more IFs to function like the bile duct epithelium to conduct bile flow.

Clinical usefulness of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field was investigated. The results obtained were summarized as follows. 1. The clinical efficacy of CFIX was investigated in a total of 138 children including 49 with upper respiratory tract infections (RTI), 22 with acute bronchitis, 18 with pneumonia, 19 with scarlet fever and 21 with urinary tract infections (UTI). 2. Clinical effectiveness was excellent in 58, good in 60, fair in 14 and poor in 3, with an overall efficacy rate of 87.4%. The efficacy rate classified according to types of infection were 85.7% in upper RTI, 89.5% in acute bronchitis, 94.4% in pneumonia, 78.9% in scarlet fever, and 90.5% in UTI. 3. Out of the suspected causative organisms, 43 strains of a total of 50 strains isolated were eradicated. The bacteriological eradication rate was 86.0%. (Haemophilus influenzae 100%, Haemophilus parainfluenzae 100%, Streptococcus pyogenes 88.5%, Escherichia coli 85.7%). 4. One hundred forty four children were analyzed for side effect. Side effects were observed in 2 children (1.4%) with diarrhea in 1 and anorexia in another. Abnormal laboratory test results were recorded in 4 children (3.3%). The above results suggest that CFIX is a very useful new oral cephalosporin for the treatment of bacterial infections in children.

Portions of eight human livers taken by wedge biopsy or needle biopsy were extracted with 0.5% Triton X-100 and then studied by scanning electron microscopy and immunoelectron microscopy. The wedge-biopsy specimens were perfused with the detergent solution. Needle-biopsy specimens were quickly frozen and cracked and then the cracked tissue was immersed in the detergent solution. The three-dimensional filament network of hepatocytes was visualized. A dense network which consisted of intermediate filaments and microfilaments was observed within the cytoplasm of hepatocytes. These filaments were better preserved in the needle biopsies which were quick-frozen and cracked before extraction than in the wedge biopsies. Variation in the amount of the cytoskeletal filaments was less prominent in the hepatocytes treated by rapid freezing. It is concluded that freeze-cracking is the most favorable method for the study of cytoskeletal pathology in various liver diseases in man.