Meigs' syndrome mimicking heart failure with preserved ejection fraction: a case report.

BACKGROUND: Meigs' syndrome is a rare disease characterized by a triad of presentations, including benign ovarian tumor, ascites, and pleural effusion. However, a clinical diagnosis of Meigs' syndrome remains challenging because pleural and ascitic effusions can be common findings in a variety of underlying conditions. Furthermore, these findings can often be misdiagnosed as pleural and peritoneal dissemination caused by potentially malignant tumors, leading to the administration of improper treatment. CASE PRESENTATION: We described a case of an 85-year-old postmenopausal female patient with atypical Meigs' syndrome presenting with right-sided pleural effusion, notable leg edema, and trivial ascites, which was initially mistaken as heart failure with preserved ejection fraction. However, pleural effusion was totally ineffective against diuretic therapy. Subsequently, thoracentesis yielded serosanguineous exudative effusion. Moreover, refractory pleural effusions and abdominal/pelvic computed tomography and magnetic resonance imaging findings strongly suggested bilateral malignant ovarian tumors with pleural dissemination. Repetitive negative cytological results allowed the patient to undergo bilateral salpingo-oophorectomy. Finally, a definitive diagnosis of Meigs' syndrome was made by confirming the presence of a benign mitotically active cellular fibroma of the ovary by pathology and that pleural effusion resolved following tumor resection. CONCLUSIONS: Our case highlights the clinical importance of assessing Meigs' syndrome in the diagnostic workup of pleural effusion in postmenopausal female patients. Given the favorable prognosis of Meigs' syndrome, clinicians should consider surgical resection, even with potentially malignant ovarian tumors with accompanying pleural effusion, ascites, or both.

[Anaphylactic shock secondary to the use of macrogol 4000 as a bowel cleanser:a case report].

A 44-year-old man was administered Niflec® containing macrogol 4000 as a bowel cleanser for colonoscopic examination. Immediately after ingestion, he experienced oral cavity discomfort and nasal congestion, followed by acute urticaria and presyncope. His systolic blood pressure and peripheral capillary oxygen saturation dropped to 66mmHg and 89%, respectively. Fluid infusion, as well as steroid and epinephrine administration, improved his symptoms. Skin prick tests were then performed using Niflec®, macrogol 4000, and Actosin® ointment (containing macrogol 4000), all of which were positive. Therefore, the patient was diagnosed with anaphylactic shock caused by macrogol 4000 included in Niflec®. Macrogol present in bowel cleansers used for colonoscopy rarely causes anaphylactic shock. However, clinicians need to be mindful of this risk. Prompt and appropriate treatment is needed should this condition occur.

[Good Controlled Chylothorax in Gastric Carcinoma].

Chylothorax has been reported to be caused by accidental injuries in half of all cases in Japan, and < 10% of these cases have been associated with malignant tumors, including lymphoma. Chylothorax is a rare complication of gastric carcinoma. We successfully treated a 58-year-old man with gastric carcinoma, chylothorax, and ascites using a combination of talc pleurodesis and a lipid-limited diet. Case: A 58-year-old man with advanced stage of poorly differentiated gastric adenocarcinoma presented to our hospital with complaints of shortness of breath. Whole-body computerized tomographic images suggested massive pleural effusion and ascites. Examination of pleural fluid and ascites revealed elevated serum triacylglycerol levels of up to 913mg/dL with numerous free-floating cancer cells. Malignant chylothorax was diagnosed. A lipid-limited diet and octreotide were started, followed by talc pleurodesis for pleural effusion. The patient with controlled pleurisy died of gastric cancer on day 55 after pleurodesis.

[The effect of routine professional oral care on oral mucositis in hematologic chemotherapy patients].

BACKGROUND: According to the literature, 40%of all oral complications associated with chemotherapy are due to oral mucositis. Moreover, such complications increase the difficulties associated with oral intake, leading to deterioration of the patient's nutritional condition and increasing the risk of systemic infection. Therefore, oral mucositis prevention and proper treatment are very important. PATIENTS AND METHODS: The conditions of intra-oral cavities and effects of oral care in patients with hematological malignancies were retrospectively evaluated by dental hygienists from April 2008 to March 2011. RESULTS: Eleven of 28 patients(39.3%)who received routine professional oral care developed oral mucositis. In many such patients, intra-oral cavity deterioration, evidenced by a coated tongue and Candida infection, was observed. Although 25 of 28 patients with hematologic malignancies received specific oral mucositis care after chemotherapy initiation, those receiving continuous oral care subsequently made a full recovery. CONCLUSIONS: These results suggest that early and continuous professional oral health care may play an important role in the effective chemotherapy of patients with hematologic malignancies.

High incidence of lung cancer death after curative endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. METHODS: This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. RESULTS: The 5-year survival rate of 187 patients was 92.6% during a median follow-up duration of 96.8 months. Thirty-one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p < 0.001). Patients with second primary lung cancer (LC) had a high mortality rate (56.3%). Univariate and multivariate analyses showed that multiple Lugol-voiding lesions (LVLs) tended to be associated with SPMs (p = 0.077, hazard ratio [HR] 4.43, 95% confidence interval [CI]: 0.91-6.50), and metachronous ESCC was an independent risk factor for the incidence of second primary LC (p = 0.037, HR 3.51, 95% CI: 1.08-11.41). CONCLUSIONS: SPMs that cannot be detected by EGD, such as LC, must be considered after the curative resection of ESCC. We suggest strict screening by both EGD and computed tomography for patients with multiple LVLs or metachronous ESCC to detect SPMs in their early stages.

Plasmablastic lymphoma occurring in ulcerative colitis during treatment with immunosuppressive therapy.

A 53-year-old man who had a history of ulcerative colitis (UC) for 2 years underwent colonoscopy as regular follow-up. The results showed an elevated lesion in the descending colon, which was diagnosed as plasmablastic lymphoma (PBL) based on pathological findings. In situ hybridization for the Epstein-Barr virus-encoded RNA probe was positive. Fluorescence in situ hybridization revealed rearrangement of the MYC gene. He had been taking prednisolone, 5-aminosalicylic acid, azathiopurine, and ustekinumab at the diagnosis of PBL and had multiple prior therapies for UC including infliximab, tacrolimus, and tofacitinib due to steroid dependence. PBL is a rare aggressive B cell lymphoma initially described in the oral cavity of human immunodeficiency virus positive patients and it is suspected to have an association with immunocompromised status of patients. The number of cases of PBL in inflammatory bowel disease (IBD) patients is extremely rare. All these patients were administered immunosuppressive therapy including thiopurines or biologics. IBD patients with immunosuppressive therapy have a higher potential for developing lymphoproliferative disorders. Clinicians should be aware of the risk of lymphoma, including PBL.

Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease.

The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25-0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26-0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Renal Dysfunction is an Independent Risk Factor for Rebleeding After Endoscopic Hemostasis in Patients with Peptic Ulcer Bleeding.

BACKGROUND: Despite the progress in endoscopic hemostasis and pharmacological treatment, the mortality rate of peptic ulcer bleeding remains at 5-10%. Rebleeding after peptic ulcer bleeding is believed to be a risk factor for mortality. This study aimed to evaluate whether renal dysfunction is a predictor of rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding. METHODS: In this retrospective study, consecutive patients with peptic ulcer bleeding who underwent endoscopic hemostasis at our Hospital from January 2010 to December 2018 were enrolled. The relationship between rebleeding within 30 days after endoscopic hemostasis and the patients' admission and endoscopic characteristics were analyzed using univariate and multivariate regression models. RESULTS: Out of 274 patients with peptic ulcer bleeding, 17 (6.2%) patients experienced rebleeding. In the analysis of the patients' admission characteristics, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 was an independent risk factor for rebleeding (odds ratio 4.77, 95% confidence interval 1.168-18.211, p = 0.03). Patients with eGFR < 15 mL/min/1.73 m2 with or without hemodialysis had the highest rebleeding rate at 36.8%. With respect to endoscopic characteristics, the rate of rebleeding was associated with combination therapy (p < 0.0001) and active bleeding (p = 0.03). CONCLUSION: Renal dysfunction might be an independent risk factor for rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding.

[A case of type 4 gastric cancer with peritoneal dissemination complicating venous thromboembolism treated effectively by combination of S-1 and warfarin].

A 49-year-old female patient was admitted to our hospital for a type 4 gastric cancer with peritoneal dissemination. Two courses of paclitaxel (PTX), and eight courses of S-1 were carried out. Although a partial response was obtained, she had complications with a deep venous thromboembolism (DVT) and pulmonary embolism (PE) during the treatment. Heparin, followed by warfarin, was useful to treat the embolism. After the venous thromboembolism (VTE) disappeared, combination therapy with S-1 and warfarin were started, and the quality of life (QOL) of this patient was maintained for about one year. Fine monitoring of the international normalized ratio (INR) was required in order to prevent side effects of blood coagulation by S-1 and warfarin coadministration. This case suggests that the combination therapy of S-1 and warfarin may be a safe and effective treatment able to prolong time to progression against a type 4 gastric cancer with VTE.

Psychologic stress and disease activity in patients with inflammatory bowel disease: A multicenter cross-sectional study.

BACKGROUND AND AIMS: Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. METHODS: This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. RESULTS: A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. CONCLUSIONS: A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.

The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells.

CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as migration, proliferation, and adhesion. In addition, it has been known that CD9 can associate with other proteins. Here we demonstrated the physical and functional association of CD9 with epidermal growth factor receptor (EGFR) on MKN-28 cells. Double-immunofluorescent staining and immunoprecipitation demonstrated the complex formation of CD9-EGFR and CD9-beta(1) integrin, and that both complexes are colocalized on the cell surface especially at the cell-cell contact site. Anti-CD9 monoclonal antibody ALB6 induced a dotted or patch-like aggregation pattern of both CD9-EGFR and CD9-beta(1) integrin. The internalization of EGFR after EGF-stimulation was significantly enhanced by the treatment with ALB6. CD9 can associate with EGFR in hepatocellular carcinoma cells (HepG2/CD9) and Chinese hamster ovary cancer cells (CHO-HER/CD9), which were transfected with pTJ/human EGFR/CD9. Furthermore expression of CD9 specifically attenuated EGFR signaling in CHO-HER/CD9 cells through the down regulation of surface expression of EGFR. These results suggest that CD9 might have an important role that attenuates EGFR signaling. Therefore, CD9 not only associates EGFR but also a new regulator, which may affect EGF-induced signaling in cancer cells.

LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobacter pylori-related enlarged-fold gastritis.

BACKGROUND: The molecular mechanism by which Helicobacter pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlarged-fold (EF+) gastritis, one cause of which is H. pylori infection, have an increased risk for gastric cancer, although again molecular mechanism is unclear. In the present study, we analyzed the methylation status of long interspersed nucleotide elements (LINE-1) and three cancer-related genes in a panel of gastric mucosae, with or without EF+ gastritis. METHODS: We used bisulfite pyrosequencing to assess the levels of LINE-1, CDH1, CDH13, and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients. RESULTS: Levels of LINE-1 methylation were significantly reduced in mucosae from patients with EF+ gastritis. This hypomethylation of LINE-1 was associated with increased methylation of the 5' CpG islands of the genes, which suggests that, in EF+ gastritis, the methylation of the promoter regions of certain genes is accompanied by global demethylation of repetitive sequences. CONCLUSIONS: Our results indicate that genomewide hypomethylation and regional hypermethylation occur in EF+ gastritis and may contribute to the tumorigenesis of diffuse-type gastric cancers.

Assessment of palliative care team activities--survey of medications prescribed immediately before and at the beginning of opioid usage.

We established the Terminal Care Study Group, consisting of physicians, pharmacists, and nurses, in September 2001, and developed the group into the Palliative Care Team. We have surveyed the state of concomitant medications immediately before and at the beginning of opioid usage (except injections) to assess the role of the Palliative Care Team. The survey period was 3 years from October 1, 2002 to September 30, 2005. While the frequency of the prescription of non-steroidal anti-inflammatory drugs (NSAIDs), laxatives, or antiemetics before the beginning of opioid administration did not differ significantly among the 3 periods, that at the beginning of opioid administration increased significantly in 2003 compared with 2002, and increased further in 2004. Many of the drugs used were those that were recommended in our cancer pain management program. Thus, the activities of the Palliative Care Team are considered to have led to proper measures for the control of the major adverse effects of opioids such as constipation and nausea/vomiting in addition to pain control in accordance with the WHO's pain ladder, and also contributed to improvements of the patients' QOL.

Prophylactic clip closure may reduce the risk of delayed bleeding after colorectal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large superficial colorectal tumors, but delayed bleeding remains one of the most common complications of colorectal ESD. The aim of the present study was to evaluate the clinical efficacy of prophylactic clip closure of mucosal defects for the prevention of delayed bleeding after colorectal ESD. PATIENTS AND METHODS: We enrolled consecutive patients with colorectal lesions between January 2012 and May 2017 in this retrospective study. In the early part of this period, post-ESD mucosal defects were not closed (non-closure group); however, from January 2014, post-ESD mucosal defects were prophylactically closed with clips when possible (closure group). The main outcome measured was delayed bleeding. Variables were analyzed using the chi-squared test, Fisher's exact test, or Student's t-test. RESULTS: Of 156 lesions analyzed, 61 were in the non-closure group and 95 in the closure group. Overall, delayed bleeding occurred in 5 cases (3.2 %). The delayed bleeding rate was 0 % (0/95) in the closure group and 8.2 % (5/61) in the non-closure group ( P  = 0.008). The mean procedure time for closure was 10.4 ±â€Š4.6 min (range 3 - 26 min). CONCLUSIONS: We demonstrated that prophylactic clip closure of mucosal defects might reduce the risk of delayed bleeding after colorectal ESD.

Age at onset is associated with the seasonal pattern of onset and exacerbation in inflammatory bowel disease.

BACKGROUND: Environmental factors are suggested to affect the pathogenesis of several diseases, including inflammatory bowel disease (IBD). The seasonality of disease onset and exacerbation in IBD, however, are not well established. We herein aimed to clarify the disease seasonality and to investigate the underlying characteristics in IBD patients exhibiting seasonality of the disease course. METHODS: This was a multicenter observational study comprising 20 institutions (Osaka Gut Forum) in Japan. Data were collected from November 2013 to August 2014 using survey forms for physicians and questionnaires for patients. Multivariate analysis was performed to clarify the independent factors affecting disease seasonality. RESULTS: A total of 1055 patients, including 298 patients with Crohn's disease (CD) and 757 patients with ulcerative colitis (UC), were enrolled. The proportion of CD patients with disease onset in the summer was significantly larger than that in the other seasons, while UC patients exhibited no seasonality of disease onset. More than half of the IBD patients (51.1%) experienced seasonal exacerbation of IBD, and winter was the most common season for disease exacerbation in both CD and UC patients. Seasonality of disease onset and exacerbation was observed in young-onset patients (≤40 years old), but not in elderly-onset patients. Age at onset was independently associated with the seasonality of both disease onset and exacerbation. CONCLUSIONS: Seasonality of disease onset and exacerbation was observed especially in young-onset IBD patients. Underlying pathophysiologic triggers for disease initiation and exacerbation may be influenced by age at disease onset.

Introduction and evaluation of a newly established holiday work system in the pharmacy ward at Municipal Ikeda Hospital.

At the Municipal Ikeda Hospital, a system in which pharmacists stationed in one ward pharmacy dispense drugs to be administered by injection and injectable preparations delivered to patients' bedsides was introduced in April 2000. This system was aimed at minimizing risks related to injections. Initially, however, on holidays, nurses played the roles of pharmacists in terms of the injections, and there were concerns over a possible rise in the incidence of errors (adverse events/near-misses) related to injections on these days compared with weekdays. Later, when planning to introduce a new holiday work system in the ward pharmacy, we took into account such factors as the number of pharmacists needed on holidays, their duties on holidays and the influence on weekday pharmacy activity of compensatory days-off taken by such pharmacists. In May 2004, the new holiday work system was introduced in the ward pharmacy. Under the new system, 5 pharmacists work at the ward pharmacy on holidays. After this system was put into operation, the number of injections dispensed at the ward pharmacy averaged 230 per day, and 177 per holiday. To evaluate the validity of this system, we recently conducted a questionnaire survey of nurses at our hospital. The survey involved 139 nurses. Of these nurses, 69.1% responded that the number of incidents (adverse events/near-misses) related to dispensing injections on holidays had decreased. Furthermore, 65.4% of the nurses reported a decrease in incidents related to the delivery and administration of injectable preparations. More than half of the nurses answered that the new system had made it easier for them to collect information on medicines and helped them provide better nursing services. When the nurses were asked to make a general assessment of the new system, 90% rated the system as "good." The results of this survey indicate that keeping the ward pharmacy open on holidays contributes to the promotion of the proper use of medicines, reduction of risks related to injections and improvement in the quality of medical care.

Gefitinib (Iressa, ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells.

Epidermal growth factor receptor (EGFR) and its ligands are involved in tumor growth, metastasis, angiogenesis, and resistance to chemotherapy. In the experiments described here using AGS gastric cancer cells, SN38 (the active metabolite of CPT-11) induced tyrosine phosphorylation of EGFR within 5 min, and this was followed by the induction of transcripts and/or proteins of heparin-binding EGF-like growth factor, amphiregulin, transforming growth factor-alpha, and interlukin-8 (IL-8). SN38 also activates nuclear factor-kappaB and activator protein-1, both of which are critical for the transcription of the IL-8 gene. However, the blocking of EGFR activation by gefitinib (Iressa, ZD1839), an EGFR-TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38-triggered mechanisms include the generation of reactive oxygen species (ROS) and the activation of protein kinase C (PKC), followed by metalloproteinase activation and the sequential ectodomain shedding of EGFR ligands. These findings suggest that EGF signaling is enhanced by CPT-11 and point to the potential benefit of the use of a combination of CPT-11 with gefitinib in the treatment of certain gastric cancers.

Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells.

The epidermal growth factor receptor (EGFR) and its ligands are involved in tumor growth, metastasis, angiogenesis, and resistance to chemotherapy. The findings reported here demonstrate that SN38 (the active metabolite of CPT-11) induces the tyrosine phosphorylation of EGFR within 5 min, followed by the induction of transcripts and/or proteins of the heparin-binding EGF-like growth factor, amphiregulin, transforming growth factor-alpha, and interlukin-8 (IL-8) in AGS gastric cancer cells. SN38 also activates nuclear factor-kappa B and activator protein-1, both of which are critical for the transcription of the IL-8 gene. However, the blocking of EGFR activation by gefitinib ("Iressa", ZD1839), an EGFR-TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38-triggered mechanisms include the generation of reactive oxygen species (ROS) and the activation of protein kinase C (PKC), followed by metalloproteinase activation and the sequential ectodomain shedding of EGFR ligands. These findings suggest that EGF signaling is enhanced by CPT-11 and point to the potential benefit of the use of a combination of CPT-11 with gefitinib in the treatment of certain gastric cancers.

Preparation and characterization of DNA hydrogel bead as selective adsorbent of dioxins.

Salmon milt DNA hydrogel beads were synthesized by an inverse suspension polymerization of acrylamide in the continuous phase of cyclohexane. These DNA hydrogel beads in water medium are stable, more than 82% (w/w) of the DNA can be retained in the hydrogel after a sufficient soaking in water. Comparing with normal adsorbents such as activated carbon and alumina, this DNA matrix showed a selective adsorptivity for the dioxin derivatives with planar structure such as dibenzo-p-dioxin (DD), dibenzofuran (DF) and biphenyl (BP). Rinsing with hexane can regenerate the DNA beads after adsorption by the dioxin derivatives, even the adsorption-regeneration process repeated four times, no significant decrease in the dioxin removal capacity was observed.

[High throughput screening of pharmacokinetics and metabolism in drug discovery (I)--establishment of assessment system for absorption to compounds with a wide diversity of physical properties].

The application of combinatorial chemistry and high-throughput screening to biological targets has led to efficient identification of lead compounds in wide therapeutic areas. However, the physicochemical properties of some lead compounds are lipophilic with low water soluble. Since these parameters determine in vivo absorption, we established robust screening methods for solubility and Caco-2 membrane permeability which are applicable to our screening strategy based on the structure-pharmacokinetic parameter relationship (SPR). Of test compounds with different core structures, turbidimetric solubility and apparent solubility as determined by HPLC-UV analysis after dilution of aqueous media from DMSO stock solution was overestimated in comparison with the corresponding thermodynamic solubility obtained using a traditional shake-flask method. A new powder-dissolution method providing thermodynamic solubility similar to that in the traditional method was developed using 96-well plates for equilibrium dialysis. The throughput of the method was the almost the same as that using the apparent solubility method. In a conventional Caco-2 assay, membrane permeability (P(app)) of some lipophilic compounds was underestimated due to low solubility in the apical site and adhesion to the device, resulting in a poor relationship between the in vivo absorption fraction and the P(app) values. The addition of 0.1% Gelucire 44/14 into the apical site and 4% bovine serum albumin into the basolateral site improved the relationship. These newly developed methods are therefore useful to optimize lead compounds with less water solubility and high lipophilicity on the basis of SPR.