Five-Year Clinical Outcomes of Low-Add-Power Segmented Rotationally Asymmetrical Intraocular Lens.

INTRODUCTION: This study assessed 5-year results of rotationally asymmetric multifocal intraocular lens (IOL) with +1.5 diopters (D) near addition (Lentis Comfort LS-313 MF15, Teleon Surgical B.V., Spankeren, Netherlands). METHODS: In 38 eyes of 20 patients (76.8 ± 4.6 years) who were examined at both 1 and 5 years after surgery, clinical data were retrospectively collected. RESULTS: Corrected and uncorrected distance visual acuity (5 m) and uncorrected and distance-corrected intermediate visual acuity (70 cm) were excellent, with no significant differences between 1 and 5 years after surgery. Uncorrected and distance-corrected near visual acuity (30 cm) remained lower. Contrast sensitivity was within the normal range at both 1 and 5 years. The percentage of patients who reported "never or hardly use spectacles" for far, intermediate, and near vision was 95.0%, 85.0%, and 35.0%, respectively. Glare and halo were slightly increased from 1 to 5 years after surgery, but the severity remained none or mild. All patients reported "very high" or "high" level of overall satisfaction. There were no notable postoperative complications. CONCLUSIONS: During 5 years after surgery, low-add-power segmented multifocal IOL maintained excellent distance and intermediate visual acuity as well as good contrast sensitivity. Glare and halo symptoms were mild, and patients' satisfaction level was high. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) identifier UMIN000048353.

Long-term outcomes of cataract surgery with toric intraocular lens implantation by the type of preoperative astigmatism.

Surgical outcomes of toric intraocular lens (IOL) implantation for 8 years after surgery were analyzed. Data were retrospectively collected in 176 eyes of 176 patients before and 1 month, 1, 3, 5, and 8 years after phacoemulsification and implantation of a toric IOL. Preoperative corneal and postoperative manifest astigmatism was analyzed by converting to power vector notations; horizontal/vertical (J0) and oblique (J45) astigmatism components. Toric IOL implantation significantly reduced pre-existing astigmatism by decreasing J0 in eyes with preoperative with-the-rule (WTR) astigmatism, increasing J0 in eyes with against-the-rule (ATR) astigmatism, and correcting J45 in eyes with oblique astigmatism. After surgery, the eyes with preoperative ATR astigmatism showed a significant ATR astigmatic shift, and J0 at 5 and 8 years was significantly smaller than that at 1 month postoperatively. Uncorrected distance visual acuity was also significantly worse at 5 and 8 years than at 1 month postoperatively. In eyes with WTR and oblique astigmatism, the effects of toric IOLs on astigmatism and visual acuity were sustained for 8 years. The long-term astigmatism-correcting effects did not differ among the models of toric IOL used in this study, SN6AT3-8 (Alcon Laboratories). In eyes with preoperative ATR astigmatism, astigmatism-correcting effects of toric IOLs decreased at 5 years and later postoperatively, indicating that overcorrection may be considered at the time of cataract surgery. In eyes with WTR and oblique astigmatism, the effects of toric IOLs were maintained throughout the 8-year follow-up period.

Prospective assessment of plate-haptic rotationally asymmetric multifocal toric intraocular lens with near addition of + 1.5 diopters.

BACKGROUND: To prospectively evaluate surgical results following implantation of rotationally asymmetric, plate-haptic, refractive segmented multifocal toric intraocular lenses (IOLs) with near addition of + 1.5 diopters (D) (Lentis Comfort LS-313 MF15T, Oculentis GmbH). METHODS: In 59 eyes of 41 patients, ocular examinations were conducted before and 1 day, 1 week, 1, 3, and 6 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were tested. A defocus curve was drawn, and the degree of disturbing photic phenomena were questioned. RESULTS: The IOL showed excellent rotational stability; the average absolute rotation was 1.66 ± 1.17 degrees from 1 day 1 to 6 months postoperatively, and 98.1 and 100% of eyes yielded rotation of less than 5 and 10 degrees, respectively. Postoperative distance and intermediate visual acuity were highly satisfactory; UDVA, CDVA, UIVA, and DCIVA were about 20/20, 20/16, 20/25, 20/25, respectively. Near visual acuity was suboptimal; UNVA and DCNVA were at approximately 20/60. The defocus curve analysis showed that 20/25 and 20/40 uncorrected visual acuity was attained at as close as 60 and 40 cm, respectively. Contrast sensitivity was within a normal range, and subjective photic phenomena were minimum. CONCLUSIONS: The refractive segmented, rotationally asymmetric multifocal toric IOLs with + 1.5 D near addition showed superb rotational stability and highly satisfactory distance and intermediate vision. Contrast sensitivity was high and incidence of photic symptoms was very low. TRIAL REGISTRATION: This study was registered at JAPIC Clinical Trials Information, ID: JapicCTI-183,877, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp (February 5, 2018).

Mid-term and long-term clinical assessments of a new 1-piece hydrophobic acrylic IOL with hydroxyethyl methacrylate.

PURPOSE: To investigate the clinical outcomes after implantation of a new hydrophobic acrylic intraocular lens (IOL) with hydroxyethyl methacrylate (HEMA) at 1 year and 9 years postoperatively. SETTING: Three surgical sites in Japan. DESIGN: Prospective case series and retrospective review. METHODS: In 110 eyes of 110 patients who underwent phacoemulsification and implantation of a new hydrophobic acrylic IOL (Clareon CNA0T0), clinical data were collected preoperatively and at 1 day, 1 week, 1 month, 6 months, and 12 months postoperatively. Of these eyes, 20 eyes of 20 patients were examined at 9 years postoperatively, and corrected distance visual acuity (CDVA) and clarity of the IOL were evaluated. RESULTS: All 110 patients (110 eyes) completed every follow-up examination up to 12 months postoperatively. At 12 months, a CDVA of 20/30 and 20/20 was obtained in 110 (100%) and 101 (91.8%) of 110 eyes, respectively. The contrast sensitivity function was better than or similar to the age-matched normal controls, and there was no case of posterior capsule opacification requiring a laser treatment. Glistenings and surface light scattering were not seen in any of these cases. At 9 years postoperatively, a CDVA of 20/40, 20/30, and 20/20 was attained in 20 (100%), 19 (95%), and 14 (70%) of 20 eyes, respectively. One eye (5%) was treated with laser capsulotomy for posterior capsule opacification. There was no case of glistenings and surface light scattering. CONCLUSIONS: This mid-term and long-term study indicated that the new hydrophobic acrylic IOL with HEMA was safe and effective with excellent postoperative vision. Glistenings and surface light scattering did not develop with this IOL in contrast to its predecessor.

Comparison of incidence of repositioning surgery to correct misalignment with three toric intraocular lenses.

PURPOSE: To compare the incidence of re-orientating surgery to improve misalignment of three models of acrylic toric intraocular lenses: AcrySof toric intraocular lens (Alcon Laboratories, Inc.), TECNIS toric intraocular lens (Johnson & Johnson Vision, Inc.) and HOYA 355 toric intraocular lens (HOYA). METHODS: In this retrospective, multicenter case series, medical charts were reviewed for collecting data on realignment surgery of toric intraocular lenses at 10 ophthalmic surgical sites in Japan. RESULTS: Over all, intraocular lens repositioning surgery was conducted in 89 of 9430 eyes (0.944%) at an average of 10.5 ± 9.7 days after the initial cataract surgery. The incidence was 0.213% (11/5155), 1.797% (62/3451) and 1.942% (16/824) with AcrySof, TECNIS and HOYA toric intraocular lenses, respectively. The incidence was significantly lower with AcrySof than with other two brands of toric intraocular lenses (p < 0.0001). In those eyes which underwent reorientation surgery, the amount of misalignment was 26.4 ± 21.9°, 29.7 ± 15.4° and 28.1 ± 20.7° with AcrySof, TECNIS and HOYA toric intraocular lenses, respectively; there was no significant difference among groups (p = 0.821). The repositioning surgery significantly reduced misalignment in all three groups. CONCLUSION: The rotational stability was considerably different among toric intraocular lenses of different manufacturers. The incidence of repositioning surgery was significantly lower with AcrySof than with TECNIS and HOYA toric intraocular lenses.

One-year clinical evaluation of rotationally asymmetric multifocal intraocular lens with +1.5 diopters near addition.

We conducted a one-year prospective, multicenter study to assess clinical outcomes after implantation of segmented, rotationally asymmetric multifocal intraocular lenses (IOLs) with +1.5 diopters (D) near addition. In this phase III clinical trial, 120 eyes of 65 patients undergoing phacoemulsification and implantation of Lentis Comfort LS-313 MF15 (Oculentis GmbH) were included. The ophthalmological examinations were performed before and 1 day, 1 week, 1, 3, 6, 9, and 12 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were measured. A defocus curve was obtained and patients were asked about the severity of photic phenomena. Postoperative distance and intermediate visual acuity was excellent, with UDVA, CDVA, UIVA, and DCIVA of approximately 20/20, 20/16, 20/25, 20/25 were attained, respectively. The level of near visual acuity was lower; UNVA and DCNVA remained at around 20/60 and 20/70, respectively. The defocus curve indicated that postoperative uncorrected visual acuity of 20/25 and 20/40 was obtained at as close as 67 cm and 50 cm, respectively. Contrast sensitivity was within the normal range, with a minimal level of subjective symptoms and high patient satisfaction. The rotationally asymmetric multifocal IOLs with +1.5 D near addition provided excellent distance and intermediate vision, but near vision was not enough for reading small prints. Contrast sensitivity was high, with very low incidences of photic phenomena and a high level of patient satisfaction.

Predictive factors for the efficacy of denosumab in postmenopausal Japanese women with non-metastatic breast cancer receiving adjuvant aromatase inhibitors: a combined analysis of two prospective clinical trials.

Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient's quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9-6.3] and 8.3% (95% CI 7.5-9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.

Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer.

Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ - 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.

Effect of denosumab on bone mineral density in Japanese women with osteopenia treated with aromatase inhibitors for breast cancer: subgroup analyses of a Phase II study.

BACKGROUND: The aim of the study was to conduct subgroup analyses of therapeutic effects of 12-month denosumab therapy on the percentage change in bone mineral density (BMD) from baseline in the lumber spine and femoral neck. MATERIALS AND METHODS: We prospectively evaluated the BMD of the lumbar spine and femoral neck of 100 hormone receptor-positive, clinical stage I-IIIA postoperative postmenopausal breast cancer patients, for whom treatment with aromatase inhibitors (AIs) as adjuvant endocrine therapy was scheduled. The primary endpoint was the percent change in lumbar spine BMD from baseline to 12 months. Patient subgroups were analyzed according to baseline variables that are known risk factors for bone loss, including previous AI therapy, age, time since menopause, baseline body mass index (BMI), and baseline BMD T-score. RESULTS: At 12 months, lumbar spine BMD increased by 4.7%; the patients who were administered AI therapy prior to denosumab (n=70) demonstrated a 4.7% increase in BMD, and the patients who received denosumab at the start of AI therapy (n=30) demonstrated a 4.5% increase in BMD (p=0.8385). Additionally, 2.4% and 1.4% increases in BMD of the right and left femoral neck, respectively, were observed. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤-1.0, >-1.0) of the right femoral neck were as follows: (2.2%, 2.5%, p=0.7773), (2.6%, 0.9%, p=0.1726), (2.5%, 2.3%, p=0.7594), (2.1%, 2.4%, p=0.2034), (2.1%, 2.9%, p=0.2034), and (2.3%, 2.7%, p=0.6823), respectively. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤-1.0, >-1.0) of the left femoral neck were as follows: (1.0%, 1.5%, p=0.1972), (1.2%, 2.7%, p=0.2931), (1.4%, 1.3%, p=0.8817), (-0.1%, 1.6%, p=0.1766), (1.3%, 1.9%, p=0.6465), and (1.5%, 1.1%, p=0.6573), respectively. CONCLUSION: Twice-yearly treatment with denosumab was associated with increased BMD among Japanese women receiving adjuvant AI therapy, regardless of the baseline characteristics or skeletal site.

Influence of surface light scattering and glistenings of intraocular lenses on visual function 15 to 20 years after surgery.

PURPOSE: To assess the long-term influence of surface light scattering and glistenings of hydrophobic acrylic (Acrysof), silicone, and poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) on visual function. SETTING: Eleven surgical sites, Japan. DESIGN: Retrospective case series. METHODS: Patients who had cataract surgery with implantation of a hydrophobic acrylic, silicone, or PMMA IOL from 1994 to 2000 were examined. Silicone and PMMA IOLs were not restricted to specific manufacturers or models. Patients were included if their corrected distance visual acuity (CDVA) within 3 months postoperatively (baseline CDVA) was 20/25 or better. The CDVA, contrast sensitivity, degree of surface light scattering measured with Pentacam densitometry, and glistening grades were recorded at the patient's latest visit. RESULTS: Of the eyes, 31 had a hydrophobic acrylic IOL, 37 a silicone IOL, and 30 a PMMA IOL. Surface light scattering and glistenings were significantly greater with the hydrophobic acrylic IOL than with silicone and PMMA IOLs (P < .0001). The CDVA at the latest visit as well as the changes in CDVA from the baseline to the latest visit did not differ between the IOLs and was unaffected by surface light scattering and glistenings, as was the contrast sensitivity. CONCLUSIONS: The hydrophobic acrylic IOL was associated with a significantly greater level of surface light scattering and glistenings than the silicone IOLs and PMMA IOLs 15 to 20 years postoperatively. However, the optical phenomena within the optics of the hydrophobic acrylic IOL did not influence the patients' visual function.

[Usefulness of Laparoscopic Stoma Creation for Unresectable Colorectal Cancer].

Laparoscopic stoma creation enables good visualization of viscera within the abdominal cavity to ensure adequate mobilization of the large intestine. Laparoscopic stoma creation/construction was indicated and performed at our hospital in 7 patients who were diagnosed with unresectable colorectal cancer between July 2015 and May 2017. Duringthe ileostomy procedure, we made a skin incision at the stoma site and performed a single-incision(3-port)laparoscopic surgery. For the colostomy procedure, we made a small incision at the umbilicus and mobilized the large intestine with laparoscopic dissection of any interveningadhesions. Operation time ranged between 34 and 127 minutes, and the volume of intraoperative blood loss was low in all cases. There were no fatal complications related to the operation. Laparoscopic stoma creation can be performed safely and may be useful for staging of malignant colorectal tumors and reducing the risk of complications.

Incidence and Outcomes of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses.

PURPOSE: To analyze the incidence and appropriate timing of repositioning surgery to correct misalignment of acrylic foldable toric intraocular lenses (IOLs). DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Patients who had undergone phacoemulsification and implantation of toric IOL at 8 surgical sites. METHODS: Patient charts were reviewed to collect data on repositioning surgery of toric IOLs. MAIN OUTCOME MEASURES: Incidence, timing, and outcomes of repositioning surgery. RESULTS: Among 6431 eyes implanted with toric IOLs, 42 eyes (0.653%) of 42 patients underwent repositioning surgery at an average of 9.9±7.5 days (range, 0-30 days) after IOL implantation. The repositioning surgery significantly reduced misalignment from 32.9°±15.7° to 8.8°±9.7° (P < 0.001), which was measured at 7.6±5.0 weeks postoperatively. Refractive cylinder was significantly reduced from 2.4±1.1 diopters (D) to 1.1±0.8 D (P < 0.001). There was a significant negative correlation between the interval from cataract surgery to repositioning procedure and the degree of residual misalignment (r = -0.439, P < 0.001). The residual misalignment was 13.1°±13.5° when the repositioning surgery was performed within 6 days after cataract surgery, whereas the residual misalignment was 6.3°±5.9° when the IOL was repositioned 7 days or later (P < 0.001). In 2 eyes that were treated within 24 hours after cataract surgery, the IOL re-rotated significantly, and additional surgical intervention was required. CONCLUSIONS: Toric IOLs were repositioned in 0.653% of cases. A relationship was found between the timing of repositioning surgery and surgical outcome. These data suggest that repositioning surgery should be performed 1 week after IOL implantation.

Effect of denosumab administration on low bone mineral density (T-score -1.0 to -2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer.

Although adjuvant aromatase inhibitor (AI) therapy is widely used in postmenopausal women with hormone receptor-positive breast cancer, it is known to be associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand, has been shown to protect against AI-induced bone loss. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. We prospectively monitored bone mineral density (BMD) of the lumbar spine and bilateral femoral necks in 100 postmenopausal women with hormone receptor-positive postoperative breast cancer of clinical stage I-IIIA in whom treatment with AI as adjuvant endocrine therapy was planned or had been ongoing. Study participants received supplemental calcium and vitamin D every day and denosumab (60 mg) subcutaneously every 6 months. At enrollment, patients were required to have evidence of low bone mass without meeting the criteria for osteoporosis. The primary endpoint was percentage change from baseline in lumbar spine BMD at month 12. At 6 and 12 months, lumbar spine BMD increased by 3.3 and 4.7%, respectively. BMD of the femoral necks also increased. Hypocalcemia of grade ≥2, osteonecrosis of the jaw, and non-traumatic clinical fracture did not occur. In conclusion, semi-annual treatment with denosumab was associated with increased BMD in Japanese women receiving adjuvant AI therapy, regardless of prior AI treatment.

Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer.

BACKGROUND: Docetaxel plus cyclophosphamide (TC) has recently been established as a standard adjuvant chemotherapy regimen for HER2-negative (HER2-) operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remain unclear. We, therefore, conducted a prospective study to evaluate the efficacy of TC NAC in HER2- primary breast cancer. METHODS: Patients who were diagnosed with HER2-, N0-N1, invasive breast cancer between July 2011 and February 2014 and had tumors measuring 1-7 cm were eligible. The subtypes were classified using a core-needle or vacuum-assisted breast biopsy. The efficacy and safety of NAC comprising TC (75 mg/m2 docetaxel and 600 mg/m2 cyclophosphamide, four cycles every 3 weeks) were investigated in a prospective study in patients with HER2- breast cancer. RESULTS: Fifty-two patients were enrolled. Of these, 94.2 % (49/52) completed four cycles of TC. The overall pCR rate was 16.3 % (8/49). The pCR rates for patients with luminal A-like breast cancer [estrogen receptor-positive (ER+), Ki67 index of <20 %, and HER2-], luminal B-like breast cancer (ER+, Ki67 index of >20 %, and HER2-), and triple-negative breast cancer [ER-negative (ER-) and HER2-] were 0 % (0/12), 4.3 % (1/23), and 50.0 % (7/14), respectively. Almost all pCRs occurred in triple-negative breast cancer patients. CONCLUSIONS: The pCR rate of TC NAC was not very high despite the high completion rate. TC NAC was effective against the triple-negative subtype, resulting in a higher pCR rate. Therefore, our results indicated that TC NAC showed limited efficacy in luminal subtype breast cancer with the exception of the triple-negative subtype.

Docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer.

BACKGROUND: The standard primary systemic therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer is anthracyclines and/or taxanes combined with trastuzumab, which demonstrates a high pathological complete response (pCR). A pCR is a predictive marker of prognosis. However, results slightly differ, depending on the hormone receptor status. The efficacy and tolerability of docetaxel, cyclophosphamide, and trastuzumab (HER-TC) as neoadjuvant chemotherapy (NAC) remain unclear. We performed a prospective multicenter study of HER-TC NAC for HER2+ primary breast cancer. METHODS: Eligible patients had a clinical diagnosis of HER2+ invasive breast cancer greater than 1 cm but less than 7 cm and a tumor stage of N0 or N1. T hey were diagnosed between July 2011 and February 2014. For NAC, four cycles of HER-TC (6 mg/kg loading dose, 8 mg/kg, 75, and 600 mg/m2) were administered intravenously every 3 weeks. We investigated the pCR of the primary breast tumors. A pCR was defined as no histological evidence of invasive carcinoma or the appearance of only ductal carcinoma in situ. RESULTS: We enrolled 42 patients. The completion rate for four cycles of HER-TC was 97.6 % (41/42 patients). The overall pCR rate was 43.9 % (18/41 patients). The pCR rate for patients with the luminal HER2 subtype [estrogen receptor (ER)-positive+, HER2+] and the HER2-enriched subtype (ER-, HER2+) was 40.0 % (8/20 patients) and 47.6 % (10/21 patients), respectively. A pCR was achieved with nearly the same probability for each subtype. CONCLUSIONS: Four cycles of HER-TC may be a NAC option for HER2-positive breast cancer.

[A case of stage IV breast cancer with long-term partial response treated with tri-weekly paclitaxel plus bevacizumab].

Paclitaxel combined with bevacizumab yields significantly better progression-free survival (PFS) in patients with metastatic breast cancer than paclitaxel alone. Here, we report a case of stage IV breast cancer with multiple liver, lung, and bone metastases maintaining a long-term partial response (PR) with tri-weekly paclitaxel plus bevacizumab administration. A 46- year-old woman treated with endocrine therapy for 21 months for multiple metastases in her lungs and bones detected 4 years after surgery for left breast cancer was referred to our hospital. New metastases were discovered in her liver. She received paclitaxel (l 90 mg/m/(2)) on days 1, 8, and 15 combined with bevacizumab (10 mg/kg) on days 1 and 15 every 4 weeks. However, during the first 3 courses, the administration of paclitaxel on day 8 was postponed to 1 to 2 weeks because of severe neutropenia. We began tri-weekly administration of paclitaxel plus bevacizumab. She continued receiving the treatment for about 1 year, without severe side effects. The PR state with good performance status was maintained. We suggest that the tri-weekly administration of paclitaxel plus bevacizumab is an effective way to maintain long-term efficacy.

[Our experience with percutaneous trans-esophageal gastrotubing (PTEG)].

Percutaneous endoscopic gastrostomy (PEG) has been generally used as a long-term enteral nutrition route for patients in whom oral intake is impossible. Percutaneous trans-esophageal gastrotubing (PTEG) is useful for the patients in whom PEG insertion has not been indicated. A gastroenterologist usually performs PTEG in Japan, but in our hospital otolaryngologists have performed this procedure. From 2006 to 2012, we experienced 9 patients who underwent PTEG insertion without a life-threatening adverse event. An otolaryngologist who is accustomed to the cervical procedures can safely perform PTEG insertion.

[A case of effective lapatinib/capecitabine therapy for HER2-positive breast cancer with multiple brain metastases].

A 63-year-old woman was suffering from HER2-positive and hormone receptor-negative breast cancer with bone metastasis. She received 16 cycles of paclitaxel(PTX 80mg/m2)plus trastuzumab(TRA 2mg/kg)on a 7-day cycle, and zoledronic acid(ZOL 4mg/body every 28 days), resulting in a near clinical complete response(cCR). Two years later, the patient complained of dizziness and nausea, and magnetic resonance imaging revealed multiple brain metastases. The prior treatments with PTX and TRA were changed to lapatinib(LAP)(orally at 1, 250mg/day every day)and capecitabine(CAP)(orally at 2, 000mg/m2 every day for 2 weeks, followed by a 1-week rest interval as 1 cycle)because of the multiple brain metastases. After 4 cycles of treatment, the number of brain lesions and the tumor sizes were significantly reduced. After 7 cycles, however, magnetic resonance imaging revealed the deterioration of some brain lesions. After whole-brain irradiation(30 Gy in 10 fractions)was added to the treatment, the outcome was near cCR. In conclusion, combination therapy of Lap and Cap may be an effective treatment option for brain metastasis of HER2-positive breast cancer.

Activation of T cell death-associated gene 8 regulates the cytokine production of T cells and macrophages in vitro.

An orphan G-protein-coupled receptor, T cell death-associated gene 8 (TDAG8) which has been reported to be a proton sensor, inhibits the production of pro-inflammatory cytokines induced by extracellular acidification. Recently, we have found that TDAG8 knockout mice showed significant exacerbation in various immune-mediated inflammation disease models. To elucidate the role of TDAG8, we screened an in-house library to find compounds which have a profile as a TDAG8 agonist using a cyclic adenosine 5'-monophosphate assay. Among the screening hits, we focused on (3-[(2,4-dichlorobenzyl)thio]-1,6-dimethyl-5,6-dihydro-1H-pyridazino[4,5-e][1,3,4]thiadiazin-5-one) (named BTB09089). BTB09089 did not act on other proton sensing G-protein-coupled receptors such as G-protein-coupled receptor 4 (GPR4) nor ovarian cancer G-protein-coupled receptor 1 (OGR1). Moreover, BTB09089 increased cAMP level in the splenocytes from wild-type littermates but not from TDAG8-deficient mice. Thus, BTB09089 was found to be a TDAG8 specific agonist. We then investigated the effects of BTB09089 on T cells and macrophages in vitro. In splenocytes, BTB09089 suppressed the production of IL-2 stimulated with anti-CD3 and anti-CD28 antibodies. In peritoneal exuded macrophages induced by thioglycollate, BTB09089 suppressed the production of TNF-α and IL-6 while it increased that of IL-10 when stimulated with lipopolysaccharide. These effects were observed in cells from wild type mice, but not those from TDAG8 knockout mice. These results indicate that activation of TDAG8 attenuates immune-mediated inflammation by regulating the cytokine production of T cells and macrophages.

[Concurrent chemoradiotherapy for resectable locoregionally advanced squamous cell carcinoma of the head and neck-analysis of factors associated with toxicity and efficacy].

We evaluated clinical factors associated with concurrent chemoradiotherapy (CRT) toxicity and efficacy in resectable locoregionally advanced squamous cell carcinoma of the head and neck. Subject were 115 subjects with stage III or IV carcinoma undergooing 58 to 70 Gy of irradiation (median total dose: 66 Gy) concurrently with 2 cycles of chemotherapy of 5FU at 1000 mg/m2, 120-hour continuous infusion and cisplatin at 60 mg/m2. Grade 3 to 4 mucositits differed significantly between 13% in N0 and 59% in N1 to 2. No significant difference in planned therapy completion was seen between 87% in N0 and 82% in N1 to 2. Three-year overall survival (OS) was 66% and progression-free survival (PFS) 55%, in median follow-up of 42 months (range: 5.8 to 91 months). OS differed significantly between 86% in stage III and 57% in IV, 78% in T0 to 2 and 62% in T3 to 4, 83% in N0 to 1 and 53% in N2, 77% in adjuvant chemotherapy (nedaplatin plus UFT) and 50% in no adjuvant chemotherapy, and 33% in the tongue and 77% in the oropharynx. PFS significantly differed between 72% in T0 to 2 and 49% in T3 to 4, 77% in CR and 53% in PR, and 22% in the tongue and 58% in the hypopharynx, 66% in the oropharynx, and 53% in the larynx. Multivariable analysis showed strongly independent risk factors associated with OS and PFS to be advanced T and N stage, no adjuvant chemotherapy, and the tongue as the site. CRT was effective in treating resectable locoregionally advanced squamous cell carcinoma of the head and neck. It is possible that adjuvant chemotherapy will improve CRT OS and PFS. Other additional treatment will be needed, however, to improve OS and PFS in cases having a dismal diagnosis such as tongue cancer.