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Findings from the published ACHEON study revealed inadequate pain relief for chronic non-cancer pain (CNCP) across 10 Asian countries/regions. Hence, we performed additional analyses on the survey data to understand management practices for relieving CNCP and treatment-related adverse events (AEs). Descriptive statistics were used to summarize patients’ profile, prescribed treatments, and associated AEs. Two-sample t test was used to compare pain levels between treatment groups. Univariate analyses were conducted to identify factors associated with pain intensity, presence of any common AEs, perceived treatment adequacy, patient-physician interaction, and employment status. Of 1305 patients surveyed, the median duration of CNCP was 24 (interquartile range, 39) months. The majority of patients (89.3%) reported having moderate (44.4%) or severe pain (44.9%). Most patients (80.1%) were prescribed non-opioids, while 16.2% of patients were untreated for pain. Although over half of the treated patients (53.8%) experienced AEs while receiving pain treatment, two-fifths were prescribed medications to manage these AEs. High pain levels, presence of AEs, and employment status influenced patients’ perception of treatment adequacy. Patients were more willing to inform their physicians when pain levels were higher and when they perceived sufficient time with physicians. These findings revealed inadequate treatment of CNCP in patients from the participating countries/regions. CNCP management may be improved through increased physician-patient interaction time and adopting a biopsychosocial model for treatment. A proactive and multidimensional approach is required to manage CNCP and potential treatment-related AEs so as to provide optimal care for patients experiencing CNCP.

Traumatic absence of the entire radial shaft in children has not been reported though there are a few reports of adult cases. We report a 5-year-old boy with traumatic absence of the entire right radial shaft. The Define's reconstruction procedure was chosen to localize the surgery only to the distal forearm and avoid further additional damage to the forearm muscles. The child's forearm was successfully reconstructed by the authors' modified Define's procedure, which was followed until his maturity. Hand function was well maintained.

Purpose To identify patterns of analgesic prescription and to explore patient-reported pain intensity, sleep disturbance, and quality of life among cancer patients with pain in Southeast Asia (SEA). Methods This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for 1 month or longer at 22 sites in Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Data on analgesic prescription and cancer characteristics were extracted from medical records. Pain intensity, sleep disturbance, and quality of life measures were recorded via questionnaires. Results Most patients (84.4%) had stage III or IV cancer. A total of 419 patients (90.7%) were prescribed opioids; of these, 42.2% received only weak opioids, whereas 57.8% received at least one strong opioid. The mean worst pain intensity during the past 24 hours was 4.76 (standard deviation [SD], 2.47) on a scale of 0 (no pain) to 10 (worst possible pain); the mean current pain intensity was 4.10 (SD, 2.61). More than half of patients (54.8%) reported sleep disturbance caused by pain in the past 7 days. The majority of patients reported problems with pain/discomfort (82.3%), usual activities (65.8%), mobility (58.2%), and anxiety/depression (56.3%). The median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine and tramadol. Conclusion Despite unrelieved pain, sleep disturbance, and issues with quality of life, a notable proportion of patients were prescribed only weak opioids, and opioid doses prescribed were generally low. Efforts focused on encouragement of prescriptions with analgesic strength and/or doses proportional to the pain management needs of patients are vital to improve the status of cancer pain management in the region.

Background We examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain. Methods This was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment. Patients started with a 5 μg/h buprenorphine patch and were titrated as necessary to a maximum of 40 μg/h over a 6-week period to achieve optimal pain control. Patients continued treatment with the titrated dose for 11 weeks. The primary efficacy endpoint was the change in BS-11 pain scores. Other endpoints included patients’ sleep quality and quality of life as assessed by the 8-item Global Sleep Quality Assessment Scale (GSQA) questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire-3 Level version (EQ-5D-3 L), respectively. Tolerability was assessed by collecting adverse events. Results A total of 114 eligible patients were included in the analysis. The mean BS-11 score at baseline was 6.2 (SD 1.6). Following initiation of TDB, there was a statistically significant improvement in BS-11 score from baseline to visit 3 (least squares [LS] mean change: -2.27 [95% CI -2.66 to −1.87]), which was maintained till the end of the study (visit 7) (LS mean change: −2.64 [95% -3.05 to −2.23]) (p

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion., Video abstract

Even in an era of remarkable medical advances, there is an issue of why tuberculosis remains in the list of disastrous diseases, afflicting humans and causing suffering. There has not been a plausible answer to this, and it has been suggested that clinicians and medical scientists could presently not win the war against the tubercle bacilli. With regards to this issue, based on the authors' own clinical and research experiences, in this review, the available literature was revisited in order to address the raised questions and to provide recent information on characteristics of tubercle bacilli and possible ways to more effectively treat tuberculosis.

Aim. The aim of this study was to examine patients’ and physicians’ satisfaction, and concordance of patient-physician satisfaction with patients’ pain control status. Methods. This cross-sectional observational study involved 465 adults prescribed analgesics for cancer-related pain from 22 sites across Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Pain intensity, pain control satisfaction, and adequacy of analgesics for pain control were documented using questionnaires. Results. Most patients (84.4%) had stage III or IV cancer. On a scale of 0 (no pain) to 10 (worse pain), patients’ mean worst pain intensity over 24 hours was 4.76 (SD 2.47). More physicians (19.0%) than patients (8.0%) reported dissatisfaction with patient’s pain control. Concordance of patient-physician satisfaction was low (weighted kappa 0.36; 95% CI 0.03–0.24). Most physicians (71.2%) found analgesics to be adequate for pain control. Patients’ and physicians’ satisfaction with pain control and physician-assessed analgesic adequacy were significantly different across countries (P<0.001 for all). Conclusions. Despite pain-related problems with sleep and quality of life, patients were generally satisfied with their pain control status. Interestingly, physicians were more likely to be dissatisfied with patients’ pain control. Enhanced patient-physician communication, physicians’ proactivity in managing opioid-induced adverse effects, and accessibility of analgesics have been identified to be crucial for successful cancer pain management. This study was registered at ClinicalTrials.gov (identifier NCT02664987).

In order to implement more effective policies for cancer pain management, a better understanding of current practices is needed. Physicians managing cancer pain and patients experiencing cancer pain were randomly surveyed across 10 Asian countries to assess attitudes and perceptions toward cancer pain management. A total of 463 physicians (77.3% oncologists) with a median experience of 13 years were included. Medical school training on opioid use was considered inadequate by 30.5% of physicians and 55.9% indicated ≤ 10 h of continuing medical education (CME). Of the 1190 patients included, 1026 reported moderate-to-severe pain (median duration, 12 months). Discordance was observed between physician and patient outcomes on pain assessment with 88.3% of physicians reporting pain quantification, while 49.5% of patients claimed that no scale was used. Inadequate assessment of pain was recognized as a barrier to therapy optimization by 49.7% of physicians. Additional barriers identified were patients' reluctance owing to fear of addiction (67.2%) and adverse events (65.0%), patients' reluctance to report pain (52.5%), excessive regulations (48.0%) and reluctance to prescribe opioids (42.8%). Opioid use was confirmed only in 53.2% (286/538) of patients remembering their medication. Pain affected the activities of daily living for 81.3% of patients. These findings highlight the need for better training and CME opportunities for cancer pain management in Asia. Collaborative efforts between physicians, patients, policy makers, and related parties may assist in overcoming the barriers identified. Addressing the opioid stigma and enhancing awareness is vital to improving current standards of patient care.

STUDY DESIGN A prospective radiographic study of cervical spine with congenital monosegment fusion. PURPOSE To evaluate the effect of cervical synostosis on adjacent segments and the vertebral morphology. OVERVIEW OF LITERATURE There are numerous clinical studies of adjacent segment disease (ASD) after monosegment surgical fusion. However, there was no report on ASD in the cervical spine with congenital monosegment synostosis. METHODS Radiograms of 52 patients, aged 5 to 90 years, with congenital monosegment synostosis (CMS) between C2 and C6, who complained of neck/shoulder discomfort or pain were studied. 51 were normally aligned and one was kyphotically aligned. RESULTS Spondylosis was not found in the patients below 35 years of age. Only 12 out of 24 patients with normally aligned C2-3 synostosis had spondylosis in 19 more caudal segments, and only one at C3-4. A patient with kyphotic C2-3 had spondylolysis at C3-4. In 8 patients with C3-4 synostosis, spondylosis was found in only 9 caudal segments (4 at C4-5, 4 at C5-6, and 1 at C6-7). The caudate C4-5 disc was the most liable to degenerate in comparison with other caudate segments. Caudal corporal flaring and inwaisting of the synostotic vertebra were the features that were the most evident. In 2 of 9 C4-5 and 7 out of 10 C5-6 synostosis patients, spondylosis was found at the two adjacent cephalad and caudate segments, respectively. Only corporal inwaisting without flaring was found. In all cases, spondylosis was confined to the adjacent segments. More advanced spondylosis was found in the immediate caudal segment than the cephalad one. CONCLUSIONS It is concluded that spondylosis at the mobile segments in a synostotic spine is thought to be a fusion-related pathology rather than solely age-related disc degeneration. Those data suggested that CMS definitely precipitated the disc degeneration in the adjacent segments.

This descriptive cross-sectional survey aims to assess the level of concordance between the perspectives of oncologists and those of patients regarding oral mucositis (OM) symptoms, and the impact of OM on various aspects of daily living and concurrent cancer management. Oncologists involved in OM management (n = 105), and patients who developed OM during cancer treatment (n = 175), were recruited from seven Asian countries. Oncologists completed a face-to-face, quantitative interview; patients completed a face-to-face interview, and a self-reported questionnaire. Oncologists and patients ranked treatment-induced OM among the three most important toxicities of cancer therapy requiring intervention. The most frequent OM symptoms reported by patients were oral ulcers (74%), dry mouth (73%), and difficulty swallowing (62%). Oncologists expected mild OM symptoms to last slightly longer than 1 week, whereas patients reported mild symptoms for more than 2 weeks. In mild-to-moderate OM, oncologists underestimated patients’ pain experience. Overall, only 45% of oncologists said they would initiate OM prophylaxis when cancer therapy started. Of the 87% of patients who said they used their prescribed medications, only 16% reported using prophylactically prescribed medication. While oncologists’ concerns related to the delays and interruptions of cancer treatment, patients tended to focus on the effects of OM on eating, drinking, and talking. Oncologists’ and patients’ perceptions about treatment-induced OM differ. To overcome discordant perspectives, there is a need to raise general awareness and improve proactive management of OM. As noted in recent guidelines, supportive cancer care is critical for ensuring optimal therapy and for improving the patient’s experience.

Background To assess the preoperative nutritional status of patients with various disorders and to provide data for pre- and postoperative patient management plans, particularly in the elderly. There is no published information on age-matched and disease-matched preoperative nutritional/immunologic status for orthopedic patients, especially in the elderly, in Jeju. Methods In total, 331 patients with four categories of orthopedic conditions were assessed: 92 elective surgery patients, 59 arthroplasty patients, 145 patients with fractures, and 35 infection patients. Malnutrition was defined as body mass index (BMI) below 18 kg/m2 of expected body weight (below 20% of normal), serum albumin/globulin ratio below 1.5 (normal range, 1.5 to 2.3), albumin level below 3.5 g/dL, total lymphocyte count below 1,500 cells/mm3, and lymphocyte/monocyte ratio below 5 versus 1. Results In 92 elective surgery patients, the average BMI was 23 kg/m2, hemoglobin was 15 g/dL, lymphocytes (2,486 cells)/monocytes (465 cells) ratio was 6.1, and the albumin (4.4 g/dL)/globulin (2.5 g/dL) ratio as a protein quotient was 1.7. Among the 59 hip and knee arthroplasty patients, the average BMI was 25 kg/m2, hemoglobin was 12 g/dL, lymphocytes (2,038 cells)/monocytes (391 cells) ratio was 6.6, and albumin (4.1 g/dL)/globulin (2.4 g/dL) ratio was 1.6. No subject showed malnutrition. Among the 145 fracture patients, the average BMI was 23 kg/m2. The hemoglobin level was 13 g/dL, monocytes (495 cells)/lymphocytes (1,905 cells) ratio was 1 versus 4.6, and albumin (4.1 d/gL)/globulin (2.5 d/gL) ratio was 1.6. However, both ratios decreased after 70 years of age. Among the 17 of 35 infection patients, albumin levels were below 3.5 g/dL, the average BMI was 22 kg/m2, lymphocytes (1,532 cells)/monocytes (545 cells) ratio was 2.4 versus 1, and albumin (3.0 g/dL)/globulin (3.3 g/dL) ratio was 0.9, while in 18 patients albumin levels were over 3.5 g/dL, the average BMI was 22 kg/m2, hemoglobin was 12 g/dL, lymphocytes (1,998 cells)/monocytes (583 cells) ratio was 3 versus 1, and albumin/globulin ratio was 1.4. Thus, in the infection group, approximately 50% of the patients showed poor nutrition and immunosuppression. Conclusions It was found that nutritional and immune condition deteriorated gradually to some degree in elderly patients over 60 years of age.

4Moon-Kim’s Institute of Orthopedic Research, Seoul, Korea Study Design: Medical record-based survey. Purpose: To survey the overall incidence of the intra- and postoperative complications and sequelae, and to propose the preventive measures to reduce complications in the spinal tuberculosis surgery. Overview of Literature: There is no study focused on the surgery-related complications and sequelae, with some touching lightly on the clinical problems. Methods: There were 901 patients in this study, including 92 paraplegics. One hundred eighty-six patients had no visible deformity, while those of 715 patients were visible. Six hundred fifty-nine patients had slight to moderate non-rigid kyphosis, and 56 had severe rigid kyphosis. Sixty-seven out of 92 paraplegics had slight to moderate non-rigid kyphosis, and 25 had severe kyphosis. There were 134 cervical and cervicodorsal lesions, 518 thoracic and thoracolumbar lesions, and 249 lumbar and lumbosacral lesions. Seven hundred sixty-four patients had primarily anterior surgeries, and 137 had posterior surgeries. Instrumentation surgery was combined in 174 patients. Results: There were intra- and postoperative complications: direct large vessel and neurological injuries (cord, roots, nerves), late thrombophlebitis, various thoracic cavity problems, esophagus and ureter injuries, peritoneum perforation, ileus, wound infections, stabilization failure, increase of deformity and late adjacent joint and bone problems. Thrombophlebitis and sympatheticolysis symptoms and signs in the lower limbs were the most common complications related with anterior lumbar and lumbosacral surgeries. Kyphosis increased in 31.5% of the non-instrumented anterior surgery cases (42% in children and 21% in adults). Conclusions: The safe, effective and most familiar surgical procedure should be adopted to minimize complications and sequelae. Cosmetic spinal surgery should be withheld if functional improvement could not be expected.

Aim To examine the treatment practices for cancer pain relief and adverse event management, and the factors related to patient outcomes in the participating countries/regions. Methods The study was a cross-sectional survey conducted between September and December 2013 in 10 countries/regions across Asia. Adult patients with a history of cancer pain at least 1 month before study entry completed the survey questionnaire. Results A total of 1190 patients were included. The mean Box Scale-11 (BS-11) pain score was 6.0 (SD 2.1), with 86.2% experiencing moderate-to-severe pain and 53.2% receiving opioids at time of the survey. The mean BS-11 scores were 5.3 (SD 2.1) in the “others” (single non-opioid medication or untreated) group, 6.3 (SD 2.0) in the ≥2 non-opioids group and 6.7 (SD 1.9) in the opioid group. The proportions of patients experiencing moderate-to-severe pain were 79.1%, 87.3% and 93.7%, respectively. About 70% of patients reported adverse events due to their pain medications, about half had received medications to manage these symptoms. Adverse events were negatively associated with activities of daily living (P < 0.0001). Pain and hindrance to activities of daily living were negatively associated with employment status (P = 0.003 and 0.021). Unemployment was significantly associated with poorer quality of life (P < 0.0001). Conclusion This analysis demonstrates inadequate management of cancer pain and treatment-related adverse events in the participating cohort. Pain and inadequate management of adverse events were negatively associated with patients’ overall well-being. More collaborative efforts should be taken to optimize pain treatment and increase awareness of adverse event management in physicians.

Spinal tuberculosis (TB) is the most common form of osteoarticular TB occurring in approximately half of all cases. It is also the most dangerous form, potentially causing paralysis, permanent neurological deficits and severe deformity. There has been a resurgence of TB over the last decade. This is mostly due to increased host susceptibility from the growing number of immunocompromised patients secondary to human immunodeficiency virus and acquired immunodeficiency syndrome, the wider use of immunosuppressant agents, the ageing population, and an increasing number of chronically debilitated patients. Although a minor factor, the recent re-emergence of multi-drug resistant variants of Mycobacterium tuberculosis hints at a possible further resurgence of TB in the coming years. Individualized treatment according to broad-spectrum management is essential for recovery. This article discusses the immunology, clinical manifestations, diagnosis, and medical and surgical treatments of spinal TB.

Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) tyrosine kinase domains. To explore the potential utility of lapatinib for the treatment of esophageal squamous cell carcinoma (ESCC), we examined the expression profiles of EGFR and HER2 in tumor tissues and in paired adjacent non-neoplastic tissues from patients with ESCC. We evaluated the antitumor effects of lapatinib alone or in combination with oxaliplatin or 5-fluorouracil (5-FU) on a panel of primary ESCC cells in vitro with various levels of EGFR and HER2 expression. The in vivo effect of lapatinib alone or in combination with oxaliplatin or 5-FU was evaluated using a primary ESCC xenograft model. EGFR was overexpressed in 80.9% (76/94) of the ESCC samples, while 24.5% (23/94) of the samples overexpressed HER2. EGFR and HER2 co-overexpression was detected in 22.3% of samples (21/94). In vitro, the primary ESCC cells were more sensitive to lapatinib combined with 5-FU or oxaliplatin than to lapatinib alone. Lapatinib in combination with 5-FU had more potent antitumor effects in the primary ESCC xenograft model, and markedly reduced the phosphorylation of EGFR and HER2, compared with lapatinib alone or in combination with oxaliplatin. These data indicate that lapatinib has activity in EGFR- and/or HER2-expressing ESCC primary cells, and that lapatinib in combination with 5-FU may be a promising treatment strategy for patients with ESCC.

Background We investigated the physicochemical properties of Medifoam® N and its wound healing performance compared to other commercially available polyurethane (PU) foam dressing in vitro and in vivo to gain insight in their clinical performance. Methods Wound contact layer and cross-section of eleven polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, moisture-vapor transmission rate (MVTR), retention and absorptivity were measured to compare physical properties. Phosphate-buffered saline (PBS) solution absorption patterns were compared. An animal model for wound-healing was applied to validate in vitro findings. Results Among eleven tested foam dressings, Medifoam® N has the smallest pore and cell sizes with excellent uniformity, i.e. it has 25 ~ 75 μm on the wound contact layer and 100 ~ 350 μm in the cross-section while other dressings have a larger pose size with larger variability. Compared to other PU foams, Medifoam® N also has moderate thickness, density, tensile strength, elongation and MVTR. Furthermore, it has excellent fluid absorption and retention capacity. These intrinsic properties of Medifoam® N contributed to improve fluid absorption patterns, i.e. other dressing material flawed out PBS solution on the dressings while Medifoam® N retained all the tested solutions. In animal wound-healing study, Medifoam® N treated animals showed excellent angiogenesis and collagen deposition even though epithelial recovery rate was not significantly different to other dressings. Conclusions Medifoam® N has optimized physical properties and thus improved fluid absorption/retention capacity. Compared to other dressings, Medifoam® N showed excellent fluid absorption patterns and these characteristics contributed to improved wound healing and excellent angiogenic potential. We found that Medifoam® N showed the best results among the employed dressing samples. Electronic supplementary material The online version of this article (doi:10.1186/s40824-016-0063-5) contains supplementary material, which is available to authorized users.

Background The aim of this study is to investigate the physicochemical and structural properties of Medifoam®Silver and to compare with other commercially available silver-containing polyurethane (PU) foam dressing in vitro. Methods Surface and cross-section of four polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, absorption rate, absorption/retention capacity and water-vapor transmission (WVT) were measured to compare physical properties of various dressing materials. Results Among four tested dressings, Medifoam®Silver has relatively uniform and smallest pore size in both surface and cross-section. In comparison of absorption properties with other dressing materials, Medifoam®Silver has rapid absorption rate, good absorption/retention capacity and good WVT value. Conclusions The data further suggests that Medifoam®Silver is a promising candidate for wound healing management.

Overexpression of the epidermal growth factor receptor-related gene ErbB2 occurs in 18% to 25% of patients with breast cancer in Western countries and is associated with a poor prognosis. The prevalence of ErbB2-positive tumors in Asia is unclear, partly because data are limited. The objective of this review was to summarize the reported prevalence of ErbB2-positive tumors from a large sample of Asian patients and to examine ErbB2 assessment methods in Asia. From searches of MEDLINE, local language journals, and local and international conference proceedings as well as locoregional breast cancer experts' recommendations, the authors selected up to 5 studies each from India, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand that reported ErbB2 results based on assessment with immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The reported prevalence of ErbB2-positive tumors in 22 studies on 24,671 patients, of whom 14,398 patients were assessed for ErbB2 status, varied widely (range, 6%-65%) as did the assessment methods used. Most studies (n = 21) used IHC to assess ErbB2 status, but definitions for positivity varied. When robust assessment methods were used, the median prevalence was 19% based on strong IHC staining (IHC3+; n = 9812 patients) and 25% based on FISH (n = 681 patients). Data on the prevalence of ErbB2-positive breast cancer in Asia are limited. The current survey indicated that the prevalence in Asia may be similar to that in Western countries; thus, up to 1 in 4 Asian patients with breast cancer potentially could benefit from ErbB2-targeted treatment. A standard, reliable ErbB2 assessment method available to patients across Asia is urgently required. Cancer 2010;116:5348–57. © 2010 American Cancer Society.

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer.

Background: The objective of the ACHEON survey was to investigate current practices in chronic non-cancer pain (CNCP) management in Asia, with a focus on opioid use. Methods: A questionnaire-based survey conducted in 10 Asian countries/regions was answered by 695 physicians managing pain (median experience: 15 years) and 1,305 patients experiencing CNCP within the preceding 3 months. Results: Overall, 89.3% of patients reported experiencing moderate-to-severe pain (median pain duration of 24 months). Continuing pain management education of ≤10 hours was reported by 71.1% of the physicians. While approximately 80% of physicians reported quantifying pain in practice, 65.0% of patients reported that no scale was used for their pain assessment. A significant proportion of physicians (78%) perceived discordance between their patients’ actual pain level and their own evaluation. Opioids were considered necessary for CNCP management by 63.6% of physicians. However, while non-opioid oral medication was prescribed to 66.8% of patients, only 4.4% of patients were prescribed opioids. CNCP was reported to affect activities of daily living for 80.8% of patients. Physicianperceived barriers to optimal therapy included patients’ reluctance to use opioids owing to fear of adverse effects (65.0%) and addiction (64.9%), while physicians’ reluctance to prescribe opioids (63.7%) was partially attributable to inadequate pain assessment (60.9%) and excessive regulation of opioids (57.3%). Conclusion: While the majority of patients surveyed reported moderate-to-severe CNCP, opioid use was suboptimal. Physician and patient education to address stigmas associated with opioid use may improve pain management practices in these countries.

Tubercle bacilli are tiny thin rod-shaped, non-spore-forming, non-motile obligate aerobic bacteria measuring 3 μm in length and 0.5 μm in width without pili for adherence and without producing adhesion molecule, and are acid-fast bacilli (AFB) with thick waxy cell wall having poorly developed porins, being present in the planktonic form. Tubercle bacilli are very slowly replicating (12 hours of generation time) only in presence of oxygen. Tuberculosis is a product of war between the host phagocytes and M tuberculosis in tissue. Phagocyte and M tuberculosis have very different cell wall composition, but both have very similar chemical weapons in them for fight and defense. Mycobacterium produces various mycolic acid compounds to form waxy cell wall and to defend it not to be digested by phagocytes, and not to be killed by the antituberculous drugs. Mycobacterium forms granuloma (tubercle) which is the specific reticuloendothelial tissue reaction to the specific type of irritants in normal person. It does not produce chondrolytic enzymes to destroy cartilage and disk, and does not adhere to any biomaterials. Thick waxy coat of Mycobacterium impedes the entry of nutrient through the poorly developed and scarce porins, and thus limits growth rate, but it also protects the bacilli from host defenses and antibiotics.

e21698 Background: Adequate dosing of analgesics is important for optimum cancer pain control & quality of life (QoL). To understand current attitudes toward analgesic treatment for cancer pain in SEA, the ACE study explored patient & physician satisfaction with pain control in 6 SEA countries. Methods: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for ≥1 month in Indonesia, Malaysia, Philippines, Singapore, Thailand, & Vietnam. Pain intensity, sleep disturbance, QoL, satisfaction with pain control, & physicians’ assessment of adequacy of analgesics were recorded via questionnaires. Current analgesic doses prescribed were extracted from medical records. Results: Most patients (84%) had stage 3 or 4 cancer. While 91% were prescribed opioids, mean reported pain intensity was 4.1 (0/no pain, 10/worst possible pain) & most had problems with sleep (55%) & QoL (problems with pain/discomfort [82%], usual activities [66%] & anxiety/depression [56%]). 60% of patients were satisfied with their pain control status & 30% found it acceptable. Physicians more often reported dissatisfaction with patients’ pain control status compared with patients (21% vs 10%). Patient-physician concordance in satisfaction with pain control was low (weighted Kappa 0.36; 95% CI 0.30-0.43). More than 1 in 4 physicians (29%) assessed prescribed analgesics to be “inadequate” for pain control. Median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine & tramadol. Of the SEA countries included, prescribed doses of opioids were generally lower in Indonesia & higher in Vietnam. Conclusions: The results highlight the complexity of managing cancer pain in SEA. Despite unrelieved pain, sleep disturbance & QoL issues, many patients still reported satisfaction with pain control. Notably, physicians expressed dissatisfaction more frequently than patients. These findings suggest a need for all-round pain status assessment (including pain intensity, sleep disturbance, QoL) & improved patient-physician communication about analgesic treatment expectations, pain control & adverse effects.

Background Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. Methods From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. Results The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). Conclusions MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.

Background ACHEON is the first and largest cross-sectional analysis conducted to determine the current practices of pain management across Asia. This survey included responses from patients suffering from cancer pain in 10 countries or regions (China, Hong Kong, Indonesia, South Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam). Methods Patients were ⩾18 years (>20 years for Korean and Taiwanese patients) with cancer pain in the last month. Patients were recruited by random selection from patient associations, patient referrals, online panels, hospital intercepts or doctor referrals. Patients were asked “yes” or “no” statements or questions with a five-point Likert scale ranging from “agree completely” to “disagree completely”. Findings 1190 cancer patients (32% male, 68% female) with a mean age of 54 years were included. Moderate-to-severe pain (median score 6 [IQR 3]) was reported by 86% of patients, while overall median duration of pain was 12 months (IQR 19). Although most patients (83%) were asked about pain by physicians at every visit, 49% of patients reported no scale was used for pain assessment. Opioid use was confirmed in 53% (285/538) of patients who remembered the type of pain medication prescribed. In all, 81% of patients claimed that pain affected their daily living (86%), and concentration and focus (87%). Furthermore, 78% of respondents were unemployed with 42% discontinuing work due to cancer pain. Among employed patients, 70% reported that pain affected work. Interpretation Cancer pain is a debilitating condition creating significant social and economic burden for Asian patients. In general, the patients surveyed had poor quality of life. Importantly, no scale was used for pain assessment in 49% of the patients. Opioids were prescribed to some patients only. This survey indicated a critical need to enhance cancer pain management via adequate assessment and therapy optimisation.

This study was carried out to assess the effect of bone marrow transplant into the 47 ununited fracture sites of the long bones of the extremities in 46 patients on bone healing. Among 46 cases, there were 43 pure fractures; a case of simultaneous ipsilateral femoral and tibial osteotomies for leg lengthening; a case of ununited repositioned cryo-treated proximal half of tibia as a limb salvage; and a case of internal transport of proximal tibia. Among the 43 pure fractures, there were 11 hypertrophic, 30 oligotrophic, and 2 gap nonunions. Bone marrow transplant was performed for any type of the delayed union and nonunion, and was also indicated in the distraction callotasis site of poor osteogenesis. Overall union rate in 43 fractures was 55.8% (24 cases). In two gap nonunions, no callus was formed. Union was obtained in all the 11 hypertrophic nonunions and 13 (46.4%) of the 30 oligotrophic nonunions. The oligotrophic and gap nonunions responded poorly to the marrow transplant. One of the two tibial osteotomy gaps healed with good evidence of endosteal callus formation. In a femoral osteotomy site for lengthening and in an ununited repositioned site of the cryo-treated tibia, there were no visible callus at all. The average time for clinical and radiological unions in the fracture cases were 5 and 7 months on average. In our series, there were no complications, including infection. The results in this series suggest that bone marrow transplant is a good source of callus formation or stimulant in treating the delayed union and hyper- and oligotrophic nonunions of any origin, and also enhances the callus formation at the gap of the early stage of the internal transport.

Colony-stimulating factors (CSFs) are commonly used for the treatment of neutropenia following chemotherapy and for the mobilization of peripheral blood stem cells (PBSC). We recently experienced a rare case of a new onset of psoriasiform eruption by GM-CSF (granulocyte-macrophage colony-stimulating factor) which was exacerbated by G-CSF (granulocyte colony-stimulating factor) in a patient with breast cancer. A 36-year-old woman had received neoadjuvant chemotherapy (cyclophosphamide, epirubicin and 5-fluorouracil), modified radical mastectomy and adjuvant chemotherapy with paclitaxel and mitoxantrone followed by GM-CSF administration for the treatment of locally advanced breast cancer. She had developed a psoriatic skin lesion on face and both upper arms during leukocyte recovery in spite of no previous history of psoriasis. Next, the chemotherapy course was complicated by a flare of mild psoriatic skin lesion, although CSF was changed into G-CSF due to GM-CSF-associated psoriasis. Subsequently, she had had high-dose chemotherapy and autologous peripheral blood stem cell transplantation for consolidation therapy. GM-CSF was administered for the mobilization of PBSC and post-transplant period, but psoriatic skin lesion did not appear. During 6 months after PBSCT, psoriasiform eruption did not appear.

e21607Background: The myelosuppressive and mucosal-damaging consequences of cancer and cancer therapies put patients at high risk of opportunistic bacterial and fungal oral infections. We explored ...

e21613Background: Oral mucositis (OM) is a common side-effect of cancer therapy. It represents not only a considerable burden on patients’ quality of life but may also limit cancer treatment. This ...

Background To evaluate efficacy in patients with brain metastasis (BM) on entry into the lapatinib expanded access program (LEAP). Methods LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily. Results Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS) was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88). In patients with BM, brain response was synchronized with systemic responses (P = 0.0001). Overall survival (OS) was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23). Multivariable analysis found hormone receptor positivity (P = 0.003) and clinical benefit rate (CBR) of combined systemic and brain disease (P Conclusion Lapatinib plus capecitabine is equally effective in patients with or without BM. Trial registration ClinicalTrials.gov (NCT00338247)

The largest burden of hepatocellular carcinoma (HCC) lies in Asia, secondary to hepatitis B virus (HBV) infection. Improved survival with sorafenib has fostered new research but many challenges remain in designing clinical trials. The disease, its management, and populations affected by it are heterogeneous worldwide and within Asia. An expert conference of Eastern Asian oncologists and hepatologists was convened to foster consensus in clinical trial design. The panel identified key areas that need to be addressed to facilitate clinical trials in Asia. Stratification by viral etiology is desirable within Asia and by region in global trials. Antiviral therapy should also be considered as a stratification factor and incorporated into HCC management in trials. The panel agreed that histological diagnosis is not required for trial entry and that Barcelona-Clinic Liver Cancer (BCLC) staging is acceptable for trials as long as portal hypertension can be better defined with standardized methodology. Consensus in treatment must be sought to allow multi-national trials and it must be recognized that first-line sorafenib is not largely feasible in Asia. Finally, Asian nations must be urged to participate in clinical trials, many of which are ongoing, to advance new treatment options in this challenging disease.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents.

6531 Background: In order to implement more effective policies for cancer pain management, a better understanding of current practices and their effects on patients are needed. The ACHEON study was...

Purpose We prospectively conducted a multi-center, open-label, randomized phase II trial to compare the efficacy and safety of docetaxel plus cisplatin (DC) and etoposide plus cisplatin (EC) for treating advanced stage non-small cell lung cancer (NSCLC). Materials and methods Seventy-eight previously untreated patients with locally advanced, recurrent or metastatic NSCLC were enrolled in this study. The patients received cisplatin 75 mg/m(2) on day 1 and either docetaxel 75 mg/m(2) on day 1 or etoposide 100 mg/m(2) on days 1 to 3 in the DC or EC arm, respectively, every 3 weeks. Results The objective response rate was 39.4% (15/38) and 18.4% (7/38) (p=0.023) in the DC and EC arms, respectively. The median time to progression (TTP) was 5.9 and 2.7 months (p=0.119), and the overall survival was 12.1 and 8.7 months (p=0.168) in the DC and EC arms, respectively. The prognostic factors for longer survival were an earlier disease stage (stage III, p=0.0095), the responders to DC (p=0.0174) and the adenocarcinoma histology (p=0.0454). The grades 3 and 4 toxicities were similar in both arms, with more febrile neutropenia (7.9% vs. 0%) and fatigue (7.9% vs. 0%) being noted in the DC arm. Conclusion DC offered a superior overall response rate than does EC, along with tolerable toxicity profiles, although the DC drug combination did not show significantly improved survival and TTP.

Eukaryotic transcriptional regulation often involves regulatory elements separated from the cognate genes by long distances, whereas appropriately positioned insulator or enhancer-blocking elements shield promoters from illegitimate enhancer action. Four proteins have been identified in Drosophila mediating enhancer blocking—Su(Hw), Zw5, BEAF32 and GAGA factor. In vertebrates, the single protein CTCF, with 11 highly conserved zinc fingers, confers enhancer blocking in all known chromatin insulators. Here, we characterize an orthologous CTCF factor in Drosophila with a similar domain structure, binding site specificity and transcriptional repression activity as in vertebrates. In addition, we demonstrate that one of the insulators (Fab-8) in the Drosophila Abdominal-B locus mediates enhancer blocking by dCTCF. Therefore, the enhancer-blocking protein CTCF and, most probably, the mechanism of enhancer blocking mediated by this remarkably versatile factor are conserved from Drosophila to humans.

CTCF, a conserved, ubiquitous, and highly versatile 11-zinc-finger factor involved in various aspects of gene regulation, forms methylation-sensitive insulators that regulate X chromosome inactivation and expression of imprinted genes. We document here the existence of a paralogous gene with the same exons encoding the 11-zinc-finger domain as mammalian CTCF genes and thus the same DNA-binding potential, but with distinct amino and carboxy termini. We named this gene BORIS for B rother o f the R egulator of I mprinted S ites. BORIS is present only in the testis, and expressed in a mutually exclusive manner with CTCF during male germ cell development. We show here that erasure of methylation marks during male germ-line development is associated with dramatic up-regulation of BORIS and down-regulation of CTCF expression. Because BORIS bears the same DNA-binding domain that CTCF employs for recognition of methylation marks in soma, BORIS is a candidate protein for the elusive epigenetic reprogramming factor acting in the male germ line.

Based on the pharmaco-physiology of the aminobisphosphonates, it could be speculated that bisphosphonates could induce not only the osteopetrotic bone disease because of their selective suppression of osteoclastic activity, but also could affect directly or indirectly the endocrine system, local factors, and also the bone metabolic turnover. Consequently, the bone fragility could be rather produced by long-term aminobisphosphonate therapy. Bisphosphonate-mediated bone disease was labeled by Odvina et al. in 2005 [Odvina CV, Zerwerth JE, Rao DS et al. Severely suppressed bone turnover; a potential complication of alendronate therapy. J Clin Endocrinol Metab 90: 1294–1301, 2005.] as the "severely suppressed bone turnover (SSBT)" on the metabolic turnover basis. However, such definition could contain various drug-induced bone diseases, and did not indicate any particular condition, induced by the bisphosphonate. The term "SSBT" is thought not solely to be based on its histology, and seems rather a clinical term applicable to the various drug-induced bone diseases. Therefore, the current authors attempted to characterize the bisphosphonate-mediated bone disease on the basis of the combined image and histological studies, and finally concluded that the prolonged bisphosphonate therapy could produce an atypical osteomalacic bone disease. (osteosclerosis of osteomalacia) which leads to fragility fracture. It is puzzling as to why malacia rather than petrosis develops in the skeleton.