Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Correlation Analysis between Hypogonadal Symptoms and Changes in Body Composition and Physical Fitness after Testosterone Treatment in Men with Testosterone Deficiency.

PURPOSE: This study analyzed changes in body composition and physical fitness in men with testosterone deficiency (TD) after testosterone treatment (TT) and examined the correlations of body composition and physical fitness with serum testosterone levels and hypogonadal symptoms. MATERIALS AND METHODS: Seventy patients with TD were divided into control (group I, n=23) and experimental (group II, n=47) groups. Patients in the experimental group were administered intramuscular testosterone enanthate (250 mg) for six months. The aging males symptom scale (AMS) score, international prostate symptom score (IPSS), body mass index, waist circumference, and serum laboratory values were measured at baseline and at the end of the study. Bioelectrical impedance analysis was used to assess the patients' body composition. Seven types of basic exercise tests were used to evaluate the patients' physical fitness. RESULTS: After six months, there were no significant differences in group I, while group II had significantly improved IPSS and AMS scores; increased hemoglobin, hematocrit, prostate-specific antigen, and testosterone levels and skeletal muscle mass; and waist circumference, and body fat mass. All elements of the physical fitness test were significantly improved in group II, with the exceptions of flexibility and endurance. Decreased waist circumference was correlated with changes in testosterone levels in group II, and the IPSS, cardiorespiratory fitness, and agility were correlated with improved hypogonadal symptoms. CONCLUSIONS: TT improved the hypogonadal and lower urinary tract symptoms in patients with TD and improved body composition, physical fitness, and metabolic syndrome parameters. Increased testosterone and improved hypogonadal symptoms were correlated with a decrease in waist circumference and an improvement in cardiorespiratory fitness and agility. As such, when implementing TT, we should consider whether these areas may be improved, as this can help to predict the effect.

Rehabilitation after Repair of Medial Meniscus Posterior Root Tears: A Systematic Review of the Literature.

Background: There is no consensus established on postoperative rehabilitation after medial meniscus posterior root tear (MMPRT) repair, including when and how physicians can apply range of motion (ROM) exercise, weight-bearing (WB), brace use, and return to sports (RTS). The purpose of this study was to systematically review the literature on postoperative rehabilitation characteristics of MMPRT repair regarding ROM, WB, brace use, and RTS. Methods: A literature search was performed using the Medline/PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. The inclusion criteria were English language, human clinical studies, and studies describing rehabilitation protocols after MMPRT repair such as ROM, WB, brace use, and RTS. Abstracts, case reports, cohort studies, controlled laboratory studies, human cadaveric or animal studies, systematic reviews, and meta-analyses were excluded. Results: Thirteen studies were included. Of the 12 ROM studies, ROM was started immediately within 1 or 2 days after operation in 6 studies and after 2 to 3 weeks of knee immobilization in the rest. Of the 13 WB studies, partial weight-bearing was initiated 1 to 4 weeks after operation in 8 studies and 6 weeks in the rest. Of the 9 brace studies, patients were immobilized by a splint for 2 weeks in 3 studies, and in the rest, a brace with full extension was applied for 3 to 6 weeks after several days of splint application. Of the 7 RTS studies, RTS was allowed at 6 months in 6 studies and 5 to 7 months in 1 study. Conclusions: This systematic review revealed conservative rehabilitation protocols were more widely adapted as ROM and WB were restricted at certain degrees during postoperative periods in most protocols analyzed. However, it is impossible to identify a consensus on rehabilitation protocols as the protocols analyzed in this review were distinct each other and heterogeneous. In the future, a well-designed comparative study among different rehabilitation protocols is essential to establish a consensus.

A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13).

BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations. METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. CONCLUSION: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations.

Does a Lower Limb Balance Test after Anterior Cruciate Ligament Reconstruction Have a Significant Correlation with Postoperative Clinical Score, Stability, and Functional Performance Test?

Background: Lower limb balance ability is reduced after anterior cruciate ligament reconstruction (ACLR). However, the recovery of balance based on functional test scores after ACLR is not known because the correlation between balance and clinical scores remains unclear. We aimed to analyze the correlation between lower limb balance assessed by functional test and clinical knee test scores after ACLR. Methods: We evaluated lower limb balance using the anterior-posterior stability index (APSI) of the Biodex Balance System (BBS). Patients underwent clinical tests to evaluate the knee, including the Tegner activity score, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and KT-2000 arthrometer measurement, hamstring per quadriceps muscle strength ratio at 60°/sec (HQ ratio), and functional performance tests (single-leg hop and single-leg vertical jump tests) 1 year after ACLR. We used a paired t-test to compare continuous preoperative and postoperative variables and Pearson's correlation coefficient to determine the relationship between BBS-APSI and clinical scores. Results: Forty-eight patients (35 men and 13 women; mean age, 28.9 ± 8.3 years) were included. The follow-up period and BBS-APSI were 12.4 ± 2.0 months and 0.9 ± 0.4, respectively. Tegner activity score, IKDC subjective score, Lysholm score, and KT-2000 arthrometer measurement improved significantly postoperatively (p < 0.001). BBS-APSI was correlated with the Tegner activity score (r = -0.335, p = 0.020), IKDC subjective score (r = -0.301, p = 0.037), Lysholm score (r = -0.323, p = 0.025), single-leg hop test results (r = -0.300, p = 0.038), and single-leg vertical jump test results (r = -0.336, p = 0.019). There was no correlation between KT-2000 arthrometer measurement and HQ ratio. Conclusions: BBS-APSI was correlated with functional performance test scores after ACLR, rendering the BBS-APSI as a useful assessment tool to evaluate postoperative functional recovery. Continuously improving balance after ACLR could be useful for functional recovery after surgery.

Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09).

PURPOSE: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. MATERIALS AND METHODS: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. RESULTS: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). CONCLUSION: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Risk factors for ocular hypertension after intravitreal dexamethasone implantation in diabetic macular edema.

We designed a retrospective observational study to identify factors associated with ocular hypertension [OHTN, defined as intraocular pressure (IOP) > 25 mmHg] after intravitreal dexamethasone (IVD) implantation in diabetic macular edema (DME) patients. We measured IOP monthly after placement of an IVD implant, and identified the trend of IOP, incidence of OHTN, and its associated systemic or ocular factors. On average, IOP was highest at 2 months after IVD implantation. Of 84 DME patients who received an IVD implant, 3 (3.57%) presented with an IOP ≥ 25 mmHg at 1 month after implantation, 6 (7.14%) at 2 months, and 2 (2.38%) at 3 months. Compared with the non-OHTN group, the OHTN group had significantly shorter axial lengths and were younger. Logistic regression analysis revealed that axial length < 23.00 mm and age < 57 years were associated with OHTN occurrence. Patients whose IOP was elevated > 30% or ≥ 20 mmHg at 1 month post-implantation, subsequently developed OHTN with statistical significance. In conclusion, shorter axial length and younger age were associated with OHTN occurrence after IVD implantation. Additionally, identifying levels or trends in IOP at 1 month after the IVD procedure may be helpful in predicting subsequent OHTN occurrence.

Incidence and seasonality of major ocular trauma: a nationwide population-based study.

We designed this study to identify the epidemiological characteristics and trends of various types of ocular trauma in the population of the Republic of Korea. We conducted a nationwide, population-based, cross-sectional study using the Korean National Health Insurance claims database for January 2010 to December 2018. We compiled the monthly numbers of patients diagnosed with hyphema and those who received open reduction surgery due to orbital blowout fracture (BOF), primary closure of the cornea or sclera (PCCS), or intraocular foreign body (IOFB) removal. We obtained annual and monthly incidence rates, and differences according to age, sex, yearly trends, and seasonal variations. The incidence rate (per 100,000 person-years) was high in the order of hyphema (18.43), BOF (11.58), PCCS (1.99) and IOFB removal (0.39). Male predominance was evident in all types of major ocular trauma, but the age distribution varied with the type: hyphemas were most prevalent at 10-14 years of age, BOFs at 25-29 years of age, and open globe injuries (OGIs) at age 60 and older. Although all types of trauma showed significant seasonality, hyphemas (amplitude: 174.81) and BOFs (23.17) showed higher amplitudes compared to OGIs (PCCS: 11.96; IOFB removal: 6.72). While the incidence of blunt trauma injuries, including hyphemas and orbital BOFs, decreased steadily from 2010 to 2018, that of OGIs showed no remarkable change.

Glucose-Regulated Protein 78 in the Aqueous Humor of Patients with Diabetic Macular Edema.

PURPOSE: We identified the associations between levels of aqueous glucose-regulated protein 78 (GRP78) and systemic or ocular factors in patients with center-involving diabetic macular edema (CIDME). METHODS: We measured the aqueous concentrations of GRP78, interleukin- (IL-) 1ß, IL-2, IL-8, IL-10, and IL-17, placental growth factor, and vascular endothelial growth factor (VEGF). We explored the associations between aqueous GRP78 levels and those of other aqueous factors, optical coherence tomography (OCT) findings, and systemic parameters in CIDME patients. RESULTS: In multivariate regression analysis, aqueous GRP78 levels were associated with aqueous VEGF levels (p = 0.007), length of EZ disruption (p = 0.007), length of EZ disruption (p = 0.007), length of EZ disruption (p = 0.007), length of EZ disruption (. CONCLUSIONS: Aqueous GRP78 levels correlated with VEGF levels in the aqueous humor and EZ disruption on OCT. However, GRP78 levels were not associated with those of inflammatory biomarkers in the aqueous humor or OCT findings. Additionally, GRP78 could not serve as a biomarker to predict short-term prognosis of anti-VEGF agent.

Factors associated with the duration of action of dexamethasone intravitreal implants in diabetic macular edema patients.

We designed this study to determine the association between the duration of action of intravitreal dexamethasone implants and aqueous humor biomarkers or optical coherence tomography (OCT) findings of diabetic macular edema (DME) patients. We measured the concentrations of interleukin (IL)-1ß, -8, -10, -17; placental growth factor; and vascular endothelial growth factor in the aqueous humor, and identified the number of hyperreflective foci (HF), grades of ellipsoid zone disruptions, and baseline central subfield thicknesses (CSTs) using OCT of patients with DME. The average duration of action of dexamethasone implants was 4.32 ± 1.18 months. In multivariate linear regression analyses, the duration of action was associated with aqueous IL-8 levels and the number of HF (ß = -0.016, p = 0.037 and ß = -0.073, p = 0.035, respectively). Multivariate logistic regression showed that the number of HF (>10) was significantly associated with a shorter duration (<4 months) of action (odds ratio: 17.17, p = 0.010). The duration of action of intravitreal dexamethasone implants in DME patients was associated with the level of aqueous IL-8 and the number of HF using OCT. Specifically, higher number of HF in the OCT was associated with a shorter duration of action.

Characteristics of diabetic macular edema patients refractory to anti-VEGF treatments and a dexamethasone implant.

PURPOSE: To determine the characteristics of diabetic macular edema (DME) patients refractory to intravitreal bevacizumab (IVB) treatments and an additional dexamethasone implant. METHODS: We classified 119 DME patients according to whether or not they are responsive to 3 consecutive monthly anti-VEGF treatments and/or an additional dexamethasone implant. We compared their concentrations of IL (interleukin)-1ß, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor as well as their optical coherence tomography (OCT) findings, and baseline characteristics. We used logistic regression analyses to identify preoperative factors related to refractoriness to treatments. RESULTS: Of 119 treatment-naïve DME patients, 50 (42.02%) patients showed responsiveness [central subfield thickness (CST) < 300µm] after 3 IVBs, and 59 (49.58%) patients showed responsiveness after an additional dexamethasone implant, but 10 (8.40%) patients showed CST 300 ≥ µm even after both treatments. Refractory DME patients showed significantly higher number of hyperreflective foci (HF) in the OCT and higher average level of aqueous IL-1ß at baseline (p<0.001 and p = 0.042, respectively). In the logistic regression analysis, higher number of HF in the OCT was associated with the refractoriness to both treatments (odds ratio [OR]: 7.03, p = 0.007). CONCLUSIONS: Higher number of HF in the OCT at the initial visit was associated with poor responses to IVBs and an additional dexamethasone implant.

A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13.

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

Open-Label, Multicenter, Phase II Study of Ceritinib in Patients With Non-Small-Cell Lung Cancer Harboring ROS1 Rearrangement.

Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization. Ceritinib 750 mg was administered once daily. The primary end point was objective response rate. The secondary end points were disease control rate; duration of response; progression-free survival; overall survival; toxicity; and concordance among fluorescent in situ hybridization, immunohistochemistry, and next-generation sequencing. Results Between June 7, 2013, and February 1, 2016, 404 patients underwent ROS1 prescreening, and 32 patients with ROS1 rearrangement were enrolled. All patients except two were crizotinib-naïve. At the time of data cutoff, the median follow-up was 14.0 months, and 18 patients (56%) had discontinued treatment. Of the 32 patients enrolled, 28 were evaluable for response by independent radiologic review. Objective response rate was 62% (95% CI, 45% to 77%), with one complete response and 19 partial responses; duration of response was 21.0 months (95% CI, 17 to 25 months); and disease control rate was 81% (95% CI, 65% to 91%). The median progression-free survival was 9.3 months (95% CI, 0 to 22 months) for all patients and 19.3 months (95% CI, 1 to 37 months) for crizotinib-naïve patients. The median overall survival was 24 months (95% CI, 5 to 43 months). Of the eight patients with brain metastases, intracranial disease control was reported in five (63%; 95% CI, 31% to 86%). The most common adverse events (majority, grade 1 or 2) for all treated patients were diarrhea (78%), nausea (59%), and anorexia (56%). Conclusion Ceritinib demonstrated potent clinical activity in patients with ROS1-rearranged NSCLC who were heavily treated previously with multiple lines of chemotherapy.

Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01).

BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. METHODS: This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. RESULTS: The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events. CONCLUSIONS: Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGC patients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964. © 2017 American Cancer Society.

Treatment outcomes of IMEP as a front-line chemotherapy for patients with peripheral T-cell lymphomas.

BACKGROUND: This study aimed to assess the treatment outcomes of ifosphamide, mesna, etoposide, and prednisolone (IMEP) combination regimen as a front-line chemotherapy in patients with peripheral T-cell lymphomas (PTCLs). METHODS: Clinical data of 38 newly diagnosed PTCLs patients who underwent IMEP at Busan Paik Hospital from January 2002 to December 2013 were retrospectively analyzed. RESULTS: The overall response rate was 68.5%, with 21 (55.3%) complete response/complete response unconfirmed and 6 (15.8%) partial response (PR). The median follow-up duration was 25.5 months (range, 0.2-87.3). The median overall survival was not reached and 2-year survival rate was 67%. The median progression free survival was 23 months. The most frequently reported adverse effects higher than grade 3 were hematologic toxicities including neutropenia (68.4%), thrombocytopenia (42.1%). There was no treatment-related mortality. CONCLUSION: IMEP regimen is effective and safe as a front-line chemotherapy in patients with PTCLs.

Langerhans Cell Histiocytosis of the Rib in an Adult: A Case Report.

Single-site, single-system Langerhans cell histiocytosis (LCH) of the rib is one of the rarest causes of bone tumor in adults. Herein, we report a case of a healthy 35-year-old male who presented with upper back pain that was attributed to a solitary osteolytic lesion at the posterolateral aspect of his sixth rib. For diagnostic confirmation and treatment, partial resection of the sixth rib was performed and pathologic finding was consistent with LCH. At the final follow-up after 2 years, no local recurrence or metastasis was observed.

Topoisomerase II alpha and microtubule-associated protein-tau as a predictive marker in axillary lymph node positive breast cancer.

AIMS AND BACKGROUND: The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. METHODS AND STUDY DESIGN: Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry. RESULTS: Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. CONCLUSIONS: We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.

G-CSF-induced myeloid cells stimulated by TLR2 enhance engraftment after allogeneic hematopoietic stem cell transplantation.

A high frequency of G-CSF-mobilized myeloid cells (gMCs) in a donor graft accelerates hematopoietic recovery after peripheral blood stem cell transplantation (PBSCT). However, because of the limited functional efficacy of gMCs, repeated transfusions of gMCs are frequently required. In this study, we investigated a strategy to improve the functional capacity of gMCs during hematopoietic engraftment after allogeneic transplantation. We found that toll-like receptor 2 (TLR2) is constitutively expressed on gMCs. Treating gMCs with the synthetic TLR2 ligand Pam(3)CSK(4) (PAM) dramatically enhanced IL-10 and TNF-α production. However, PAM treatment does not induce substantial cellular maturation. Moreover, PAM treatment significantly improved gMC survival. PAM treated gMCs significantly promoted myeloid differentiation of donor hematopoietic stem cells (HSCs), resulting in accelerated engraftment after allogeneic transplantation. Our data suggest that TLR2-stimulated gMCs may be a novel cellular therapeutic for increasing the efficiency of allogeneic hematopoietic stem cell transplantation (HSCT) by reducing infectious complications associated with delayed engraftment.