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Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease with a high disease burden, is one of the most common dermatological conditions in Japan. Herein, we report the disease profiles and current AD treatment during 2-year management of Japanese adults with moderate-to-severe AD. ADDRESS-J was a prospective, longitudinal, observational study that evaluated real-world effectiveness and safety of current AD treatments of adult patients with moderate-to-severe AD (Investigator's Global Assessment score 3 or 4) in Japan. The maximum follow-up period was 2 years. Among 300 patients enrolled, 288 had ≥1 post-baseline evaluation and were analyzed (mean age, 35.5 years; 60.1% male). Almost all patients (99.7%) received topical therapy; the most commonly used therapy was topical corticosteroids of the second-highest potency (86.5%) (e.g., 0.1% mometasone furoate) followed by medium-potency topical corticosteroids (50.3%) (e.g., 0.05% clobetasol butyrate). At month 12 of the study, 10.4% of patients had Investigator's Global Assessment 0/1, similarly at month 24 (10.8%). A total of 132 patients (45.8%) had ≥1 AD flare-up during the observation period, with the majority of first flares occurring within the first year of the study. Various physician- and patient-reported outcomes improved considerably during the first 3 months of the study, with only minor changes after this time. In this cohort, 16.7% of patients had skin infections requiring treatment; 7.3% had adverse events (AE) potentially related to treatment; 1.7% had serious AE; and 1.0% had treatment discontinuations due to AE. Limitations include missing data at later timepoints and the inclusion criteria limiting generalizability. In summary, this analysis of the ADDRESS-J study showed that some patients with moderate or severe AD respond to conventional therapies, while others do not. For those with inadequately controlled moderate-to-severe AD, the newly emerged systemic agents, such as biologics, may provide a potential strategy for long-term disease management.

The predictive importance of galectin-3 in non-small cell lung cancer (NSCLC) has not been elucidated. We examined whether galectin-3 could serve as a predictor for tumor recurrence in NSCLC. In 42 consecutive patients with NSCLC who underwent radical resection, galectin-3 expression in tumor cells was examined by immunohistochemistry. Galectin-3 levels in serum were assessed before surgery and 1 month after surgery by enzyme-linked immunosorbent assays. Higher expression of galectin-3 in tumor cells was associated significantly with lymphatic invasion (p = 0.049) and tumor recurrence (p = 0.001). The Kaplan–Meier curves for relapse-free survival after radical resection showed that patients with high expression of galectin-3 had significantly shorter relapse-free survival than those with low expression of galectin-3 (p

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non-small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I-IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.

A 53-year-old man underwent surgical repair and drainage of a spontaneous esophageal rupture through a left anterolateral intercostal thoracotomy. Thereafter, wound infection persisted for 3 years with formation of cutaneous fistulae and granulation tissue. Chest computed tomography revealed osteolysis, swollen ribs and costal cartilage, and cutaneous fistulous tracts. Bone scintigraphy with 99mTechnetium revealed abnormal accumulation in the ribs and costal cartilage, indicating costochondritis and osteomyelitis of ribs with cutaneous fistulae. Surgical resection of the skin including the cutaneous fistulae, infected ribs and costal cartilage were performed successfully.

BACKGROUND\ud Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits\ud signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important\ud drivers of atopic or allergic diseases such as atopic dermatitis.\ud METHODS\ud In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1\ud and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose\ud disease was inadequately controlled by topical treatment. Patients were randomly\ud assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg)\ud or placebo weekly or the same dose of dupilumab every other week alternating\ud with placebo. The primary outcome was the proportion of patients who had both\ud a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment\ud and a reduction of 2 points or more in that score from baseline at week 16.\ud RESULTS\ud We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary\ud outcome occurred in 85 patients (38%) who received dupilumab every other week and\ud in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received\ud placebo (P

Objectives Cancer-associated fibroblasts (CAFs) are a dominant cell type in tumor stroma and support the generation of pro-tumorigenic microenvironment. CAFs have frequent opportunities to interact with immune cells infiltrating the tumor stroma, but the process remains to be determined. In this study, we focused on immune checkpoint mechanism. We also examined the induction of programmed cell death-ligand 1 (PD-L1) on CAFs by immune cell, and the clinical significance of PD-L1-expressed CAFs in non-small cell lung cancer (NSCLC). Materials and methods CAFs were isolated from human NSCLC tissues, and PD-L1 expression levels in CAFs were analyzed by real-time polymerase chain reaction and flow-cytometry. Following immunohistochemical analysis of PD-L1 in surgically resected pN0M0 NSCLC (n = 125, including 88 invasive adenocarcinomas and 37 squamous cell carcinomas), the correlation of PD-L1-positive CAFs with clinicopathological features was investigated. Results PD-L1 mRNA and protein expression on CAFs was upregulated by exogenously supplemented interferon-gamma (IFN-γ) and downregulated through the depletion of IFN-γ. PD-L1 expression on CAFs was upregulated by co-culture with activated lymphocytes releasing IFN-γ. Immunohistochemistry revealed that PD-L1-positive CAFs were observed in 31 cases (24.8%). Postoperative relapse-free survival was significantly prolonged in patients with PD-L1-positive CAFs as compared with those with PD-L1-negative CAFs, with 5-year relapse-free probabilities of 84.5% and 66.3%, respectively (P = 0.031). Multivariate analysis revealed that PD-L1 expression on CAFs was an independent prognostic factor of longer relapse-free survival after surgery (hazard ratio: 3.225, P = 0.027). Conclusion PD-L1 expression on CAFs is reversibly regulated by environmental stimuli including IFN-γ from activated lymphocytes. In the non-metastatic NSCLC, PD-L1 expression on CAFs suggests the induction of anti-tumor immune responses, contributing to better prognosis after surgery.

What is known and objective Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). Methods We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. Results and discussion The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. What is new and conclusion There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.

A 16-year-old male high-school student experienced generalized itchy wheal and dyspnea during physical exercise after lunch. Each food material of his lunch was examined using a prick-prick test, allergen-specific IgE test (ImmunoCAP

Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized.\ud \ud Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL.\ud \ud Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness.\ud \ud Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p

Background: Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Objectives: To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. Methods: A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Results: Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–

Purpose The purpose of this study is to evaluate the accuracy of gastrointestinal (GI) perforation ICD-10 coding in the Diagnosis Procedure Combination (DPC) database and to examine drug exposure risk factors for GI perforation. Methods A total of 100 patients with GI perforation ICD-10 codes were selected randomly from Kagawa University Hospital's DPC database between April 2011 and December 2016. Two experienced specialist physicians independently reviewed the medical records and classified cases as "definite A," "definite B," "probable," or "no GI perforation." The positive predictive values (PPVs) of "definite A/B" cases were calculated after stratification by sex, age, ICD-10 code, and diagnostic information in the DPC data. The number of prescribed drugs with side effects of GI perforation according to historical data was compared between "definite A/B" and "no GI perforation" cases. Results The overall PPV was 47.0% (95% confidence interval [CI], 36.9-57.2). However, the PPVs for the three categories of diagnostic information in the DPC data ("main diagnosis," "diagnosis causing admission," and "most resource-intensive diagnosis") were each more than 70% after excluding inappropriate patients. Additionally, the PPV focused on these three categories was 76.3% (95% CI, 59.8-88.6). Prescribed drugs with side effects of GI perforation were more frequently detected in "definite A/B" cases (P = .028). Conclusions Although the overall PPV for GI perforation based on ICD-10 code was low, our results suggest that the PPV could be improved by appropriate selection of DPC diagnosis category and that use of multiple medications enhances the risk of GI perforation.

Galectin‑3 plays crucial roles in tumor progression. However, in non‑small cell lung cancer (NSCLC), it remains unclear whether the hypoxic tumor microenvironment enhances galectin‑3‑induced cell motility. We investigated galectin‑3 expression in NSCLC cells under hypoxia, and the possible molecular mechanisms by which galectin‑3 influences tumor aggressiveness. Galectin‑3 levels in NSCLC cell lines under hypoxia were assessed using reverse transcription PCR and western blotting. To clarify the role of endogenous galectin‑3, the effect of galectin‑3 knockdown in NSCLC cells was investigated using scratch and invasion assays. The expression and clinicopathological significance of galectin‑3 in 57 patients with pN0M0 invasive pulmonary adenocarcinoma were investigated by immunohistochemistry. Both mRNA and protein levels of galectin‑3 in the NSCLC cell lines A549 and LK‑2 were upregulated by hypoxia. As revealed by scratch and invasion assays, the cell migratory and invasive activities were significantly increased under hypoxia, but were reduced by galectin‑3 knockdown. Notably, addition of galectin‑3 to the media did not improve the cell motility impaired by galectin‑3 knockdown. To clarify the role of endogenous galectin‑3 in the enhancement of tumor cell motility under hypoxia, we focused on the function of RhoA. RhoA level in the plasma membrane, but not in the cytoplasm, was increased under hypoxia and decreased by galectin‑3 knockdown. RhoA activity was significantly enhanced under hypoxia and effectively inhibited by galectin‑3 knockdown. In patients with pN0M0 invasive pulmonary adenocarcinoma, higher galectin‑3 expression on tumor cells was significantly associated with tumor cell invasion into microvessels and tumor recurrence after surgery. These data demonstrate that in NSCLC cells under hypoxia, upregulated galectin‑3 levels increase the localization of RhoA to the plasma membrane, thus enhancing RhoA activity, which is associated with aggressive cell motility. In pN0M0 invasive pulmonary adenocarcinoma, galectin‑3 is a potential biomarker for predicting tumor recurrence after radical surgery.

Case: 72-yr-old manChief complaint: Breathing difficulty with wheezingwhen cutting Falcata.Personal medical history: Eczema since infancy.Tubercular pleurisy at the age of 28.Family medical history: Nothing of special note.Occupational history: Worker in wood furnitureproduction. Had been working with wood sincegraduation from junior high school.Working inpresent position since the age of 18.Smoking status: Nonsmoker, both present and past.Alcohol consumption: One bottle of beer and twoglasses of brandy every day.Pets: None.History of present illness: The patient had bronchialasthma at the age of 17. The main symptom was coughingwith slight breathing difficulty. At 30 yr of age, he wasstruck by a severe asthma attack, and was unconsciousovernight. From that time, his asthma attacks appearedonly at the turn of the season. Control by drug therapywas excellent for about ten years from when he was 60yr old, and there were no asthma attacks. The patientbecame conscious of breathing difficulty with wheezingafter entering the factory at the age of 70 yr. He began toregularly visit a local doctor’s office once a week. Hedid not have the complaint of itchy eyes. Theophyllinetablets were prescribed three times a day after each meal.Becromesazon inhalation medicine and Predonizorontablets were prescribed for use during an attack. Recently,he noticed that the symptoms appeared when cuttingFalcata with a circular saw. He could not enter the factorywhen Falcata was being cut. His symptoms appearedeven if he entered the factory without knowing thatFalcata had been cut. The severity of his symptomsgradually decreased when he left the factory and did notappear with wood other than Falcata. His symptomsdisappeared after the processing of Falcata wasdiscontinued.Two other employees also complained of sneezing,runny nose and voice change after cutting Falcata.However, they did not suffer from breathing difficultywith wheezing. Employees at other factories have alsocomplained of sneezing and runny nose after handlingFalcata.To confirm the diagnosis of occupational asthma (OA)induced by Falcata, the patient was hospitalized at theOsaka Prefectural Medical Center for Respiratory andAllergic Diseases on September 12, 2005. Signedinformed consent was obtained from the patient for thisstudy and the bronchial provocation test. This study andthe bronchial provocation test were approved by theHospital Ethics Committee. Findings on admission: Height 160.8 cm, weight 60Kg, temperature 36.5 °C, pulse 76 beats per minute, bloodpressure 140/75 mmHg, SpO

We reported a case of surgically resected double bronchogenic cysts within the anterior mediastinum. An anterior mediastinal tumor had been found at medical examination 6 years ago in a 66-year-old man, but has been followed up without treatment. After the treatment of another disease, he was referred to our hospital for evaluation of the mediastinal tumor. A chest computed tomography showed 2 anterior mediastinal nodules. Nodules in the thymus were resected with video-assisted thoracic surgery. The tumors were both pathologically diagnosed as bronchogenic cysts.

Genes of the IL-1 family encode three different peptides, IL-1alpha, IL-1beta, and IL-1Ra, respectively. IL-1 operates through IL-1RI, and is involved in airway inflammation in asthmatic subjects, whereas IL-1Ra appears to be a specific competitive inhibitor of IL-1. All genes are on chromosome 2q12-21 where genomewide searches have identified linkage for asthma. To test whether variants of IL-1 relate to asthma, we conducted a genetic association study in a Japanese population. We show that the A2 allele of IL1RN (encoding IL-1Ra) associates with nonatopic asthma [OR = 5.71, 95% CI: 1.63-19. 8, Pc = 0.007]. Both atopic and nonatopic asthmatics with the A2 allele had significantly lower serum IL-1Ra levels in both types of asthmatics. Peripheral blood cells from asthmatics with A2 alleles, however, produced as much IL-1 as did those with A1 homozygotes. Since Th1 and Th2 cytokines differentially regulate the ratio between IL-1beta and IL-1Ra, these findings suggest that dysregulation of IL-1beta/IL-1Ra, probably due to interaction between epithelium and immuno-competent cells in the airway, is important in asthma inflammation.

An abnormal shadow was detected in a 75-year-old man on a chest roentgenogram, and the patient was referred to our institution. A transbronchial biopsy was carried out and the specimen resulted in a diagnosis of organizing pneumonia. During the follow-up period, the left lung lesion became enlarged. Partial resection of the left lung was performed. Postoperatively, pathological examination of the tumor showed an organizing pneumonia. Approximately 3 years later, a new calcified heterogeneous mass shadow was detected in the left lung and left pleura, which had gradually enlarged. Computed tomography (CT)-guided fine-needle biopsy of the nodule of the left pleura was performed. Microscopically, the specimen led to the diagnosis of low-grade osteosarcoma. Re-evaluation of the primary and secondary lesions were confirmed as the same histopathological findings. A further systemic examination was performed. Finally, the lesion was confirmed as low-grade osteosarcoma of the lung. The patient refused further treatment and died due to respiratory failure.

We herein report a case of advanced hepatocellular carcinoma (HCC) with Vp4 portal vein thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 68-year-old man was referred to our institution in May 2009. The abdominal CT scan demonstrated massive HCC in the right robe of the liver with PVTT reaching the portal trunk (Vp4). We semi-electively performed a right hepatectomy together with thrombectomy of the PVTT. Subsequently, we underwent a PIHP (doxorubicin 90 mg/m2). This resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT.

We report a long-term survival case of hepatocellular carcinoma (HCC) with recurrence in the liver and multiple lymph nodes treated with lymph node dissection and percutaneous isolated hepatic perfusion (PIHP). The patient was a 70-year-old man with HCC. In 1999, transcatheter arterial chemoembolozation (TACE) was performed for HCCs. In 2000, partial hepatectomy was achieved for a recurrence in the liver. In 2002, CT scan disclosed multiple lymph node metastases around the hepatic artery and the recurrence in the liver. We performed a lymph node dissection and radio-frequency ablation for the hepatic tumor. After the operation, PIHP was performed for residual lymph node metastases. Then, a recurrence in the liver occurred 3 times, but was treated successfully with local therapy. The patient survives for 10 years after the initial therapy, and 8 years after a lymph node dissection.

We report a case of TS-1-resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan (CPT-11) combination therapy. A 72-year-old man underwent total gastrectomy with pancreaticosplenectomy for advanced gastric cancer on October 18, 2001, and partial hepatectomy for postoperative liver metastasis on August 22, 2002. In March 2004, a chest computed tomography scan revealed metastatic lesions in the bilateral lungs, and he received a single administration of TS-1, resulting in partial response. After 13 courses, this therapy was discontinued due to progressive disease. Then,TS-1 and CPT-11 combination therapy was chosen as the second-line chemotherapy. After 4 courses, a partial response was obtained in lung metastasis, and thereafter has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. TS-1 and CPT-11 combination therapy could be a promising regimen as the second-line chemotherapy for gastric cancer resistant to TS-1.

Nucleotide sequences surrounding the trans-spliced leader SL1 exon in the 5S rRNA gene spacer regions of Dirofilaria immitis, Brugia malayi, and B. pahangi were determined after PCR amplification, aligned with the genus Onchocerca for comparison, and used for the prediction of secondary structures. The nucleotide sequence of this region in B. pahangi was first shown in the present study. Hypothetical secondary structures of the spacer region suggested that the SL1 transcript is capable to form a stable stem-loop structure which may render transposition of the SL1 sequence to mRNA molecules. A homologous sequence to Sm-binding site was assigned on a bulge loop. No significant difference was observed in adult worms of D. immitis irrespective of sex or location. No difference was apparent between the two species in genus Brugia.