Bronchovascular bundle thickening on CT as a predictor of survival and brain metastasis in patients with stage IA peripheral small cell lung cancer.

AIM: To determine if bronchovascular bundle (BVB) thickening on pretreatment computed tomography (CT) images helps predict survival in patients with peripheral small cell lung cancer (pSCLC) ≤3 cm. MATERIALS AND METHODS: The pretreatment CT examinations of 79 histopathologically proven pSCLC ≤3 cm (TNM stage I, 21; II, 13; III, 22; IV, 23) were reviewed retrospectively. The CT characteristics of the nodule and associated findings, including BVB thickening, were evaluated. Progression-free survival (PFS), overall survival (OS), and brain metastasis-free survival were compared with the presence of BVB thickening using Kaplan-Meier and Cox regression analysis. RESULTS: Among the 79 patients, 34 (43%) had BVB thickening. BVB thickening was prevalent in patients with mediastinal lymph node metastasis (50.9% versus 22.7%; p=0.024) and distant metastasis (60.9% versus 35.7%; p=0.049). Out of the 21 patients with TNM stage IA disease, the 16 patients (76.2%) without BVB thickening showed better PFS, OS, and brain metastasis-free survival (mean, 1,762 versus 483 days; p=0.019: 2,243 versus 1,328 days; p=0.038: 2,274 versus 1,287 days; p=0.038, respectively). Multivariate Cox regression analysis showed that the absence of BVB thickening (hazard ratio [HR], 7.806; 95% CI, 1.241-49.091; p=0.029) and surgery (HR, 0.075; 95% CI, 0.008-0.746; p=0.027) were independent and useful prognostic factors for PFS. CONCLUSIONS: BVB thickening was found more frequently in patients with advanced-stage pSCLC ≤3 cm, and the PFS was more favourable in patients without BVB thickening, with a similar tendency to that of OS and brain metastasis-free survival, in stage IA pSCLC.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial.

BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).

Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17).

BACKGROUND: Pemetrexed has shown a favourable response rate of about 30% with minimal toxicity when used as a single agent for treatment of advanced urothelial carcinoma. This phase II study evaluated the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. METHODS: This multicentre, single-arm, open-label, phase II clinical trial enrolled patients who had advanced urothelial carcinoma, ECOG PS 0-2, and measurable disease. Pemetrexed 500 mg m(-2) with cisplatin 70 mg m(-2) on day 1 were administered every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 42 patients were enrolled (median age, 66 years; ECOG 0-1, 100%; visceral metastasis, 54.8%; recurrent disease, 57.1%). Twenty-seven partial responses for an ORR of 64.3% (95% CI, 49.2%-77.0%) were documented. Seven patients had stable disease. Median PFS and OS were 6.9 (95% CI, 6.2-7.6) and 14.4 (95% CI, 10.4-18.4) months, respectively. Grade 3 or 4 neutropenia was observed in 28.6% of patients. No patients experienced febrile neutropenia. CONCLUSION: The combination of pemetrexed and cisplatin is active, and well tolerated in patients with advanced urothelial cancer as a first-line treatment.

RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial.

BACKGROUND: The standard sunitinib schedule, 4 weeks on, followed by 2 weeks off (4/2 schedule), is associated with troublesome toxicities, and maintenance of adequate sunitinib dosing and drug levels, which are essential for achieving an optimal treatment outcome, is challenging. The objective of this study was to investigate the efficacy and safety of an alternative sunitinib dosing schedule of 2 weeks on and 1 week off (2/1 schedule) compared with the standard sunitinib schedule of 4 weeks on and 2 weeks off (4/2 schedule). PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase II trial, treatment-naïve patients with clear-cell type metastatic renal cell carcinoma (mRCC) were randomly assigned to 4/2 or 2/1 schedules after stratification by Memorial Sloan Kettering Cancer Center risk group and the presence or absence of measurable lesions. The primary end point was the 6-month failure-free survival (FFS) rate, determined by intention-to-treat analysis. RESULTS: From November 2007 to February 2014, 76 patients were accrued, and 74 were eligible. FFS rates at 6 months were 44% with the 4/2 schedule (N = 36) and 63% with the 2/1 schedule (N = 38). Neutropenia (all grades, 61% versus 37%; grade 3-4, 28% versus 11%) and fatigue (all grades, 83% versus 58%) were more frequently observed with schedule 4/2. There was a strong tendency toward a lower incidence of stomatitis, hand-foot syndrome, and rash with schedule 2/1. Objective response rates (ORRs) were 47% in schedule 2/1 and 36% in schedule 4/2. With a median follow-up of 30.0 months, the median time to progression (TTP) was 12.1 months in schedule 2/1 and 10.1 months in schedule 4/2. CONCLUSION: Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed.

BACKGROUND: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate. RESULTS: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).

Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients.

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.

Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma.

BACKGROUND: Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). PATIENTS AND METHODS: Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). RESULTS: Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. CONCLUSIONS: Sunitinib has promising activity in patients with nccRCC (NCT01219751).

Metastatic cervical adenocarcinoma mimicking retroperitoneal sarcoma of the psoas muscle on imaging.

BACKGROUND: The incidence of bone metastasis is low in metastatic cervical cancer, especially in the case of adenocarcinoma. Incidental finding of a mass located in an unusual metastatic site in the absence of identifiable primary tumor often results in a difficult diagnostic problem. CASE REPORT: We report the case of a 59-year-old woman presenting left-sided foot drop as her initial symptom. At first, after performing lumbar spine magnetic resonance imaging (MRI), a huge paravertebral mass with ipsilateral psoas muscle involvement suggesting retroperitoneal sarcoma was identified. However, cervical punch biopsy and sono-guided paravertebral mass biopsy revealed cervical adenocarcinoma with lumbar spinal metastasis. CONCLUSION: Although rare, a neurological symptom such as foot drop, not vaginal symptoms, in a woman may be a first manifestation of metastatic cervical cancer, especially in spinal metastasis. Furthermore, any abnormal lesion should not be ignored because of the possibility of metastasis from the primary malignancy, especially in the current case of cervical adenocarcinoma, so a complete evaluation is always mandatory.

Successful salvage treatment of recurrent endometrial cancer with multiple lung and abdominal metastases.

The prognosis of recurrent endometrial carcinoma is generally poor except for isolated vaginal or pelvic relapse without previous radiation. Recurrences associated with infield failure or distant metastasis carry a poor prognosis. We report a case of recurrent endometrial carcinoma treated with cytoreductive surgery, targeted radiation to lung metastasis defined by CT and PET and adjuvant chemo-hormone therapy followed by maintenance progestin therapy with a good outcome. This case implied that chemo-hormone therapy with targeted radiation should be evaluated in recurrent endometrial cancer with positive progesterone receptor for salvage treatment.

Diffuse intraabdominal fibrosis and inflammation mimicking peritoneal carcinomatosis recurred after surgery for borderline ovarian tumor misdiagnosed by 18F-fluorodeoxyglucose-positron emission tomography.

BACKGROUND: 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) adds to conventional imaging in the detection and staging of peritoneal carcinomatosis. CASE REPORT: Herein we report a 27-year-old woman with multiple intraperitoneal masses detected by 18F-FDG-PET, suggesting peritoneal carcinomatosis. She had undergone laparoscopic unilateral oophorectomy for a left ovarian mucinous borderline tumor approximately five years before. Based on imaging and intraoperative findings, multiple intraabdominal masses strongly suggested peritoneal recurrence from a previous ovarian borderline tumor, but it finally proved to be inflammation and fibrosis on histopathologic examination. CONCLUSION: Although 18F-FDG-PET is well known to be a highly sensitive imaging tool for identification of peritoneal carcinomatosis, FDG uptake is not tumor-specific. Therefore, the possibility of a false-positive diagnosis due to benign conditions, such as inflammation, should always be taken into consideration.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODS: Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTS: Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONS: Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Evaluation of the potential use of adipose-derived mesenchymal stromal cells in the treatment of canine atopic dermatitis: a pilot study.

Stem cells and their potential therapeutic uses in human and veterinary medicine have generated considerable interest. These cells have a number of potentially unique immunologic properties; most notable are their reported regenerative and antiinflammatory capabilities. The aim of this prospective pilot study was to evaluate the efficacy of intravenously administered autogenous adipose-derived mesenchymal stem cells (AD-MSCs) in the treatment of canine atopic dermatitis. AD-MSCs administered intravenously at a dose of 1.3 million cells/kg did not significantly reduce the clinical signs of canine atopic dermatitis or the owner-assessed pruritus level.

Hot hydrogen atoms: initiators of reactions of interest in interstellar chemistry and evolution.

Photochemically generated hot hydrogen atoms initiate reactions with simple molecular substrates including methane to produce organic alcohols, amines, acids, amino acids, and other compounds. The typical quantum yields for the formation of amino acids are 2 x 10(-5) to 4 x 10(-5). Hot hydrogen atoms may be important initiators of reactions in interstellar space and in planetary atmospheres.

Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like synoviocytes.

OBJECTIVE: Resveratrol is a naturally occurring polyphenol, which possesses chemotherapeutic potential through its ability to trigger apoptosis. The objective of this study was to investigate the major determinant for the apoptotic cell death induction by resveratrol in fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: The effect of resveratrol on apoptotic cell death was quantified in a population of subG1 in RA FLS by flow cytometry. The underlying signalling mechanism for apoptotic death was examined by analysing mitochondrial membrane potential, activation of the caspase cascade and translocation of Bid. RESULTS: We show that activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in RA FLS. Our findings also suggest that this enhanced apoptosis caused by resveratrol occurred in RA FLS irrespective of p53 status. Exposure to resveratrol caused extensive apoptotic cell death, along with a caspase-dependent (activation of caspase-9 and -3, poly ADPribose polymerase (PARP) cleavage and mitochondrial cytochrome c release) or caspase-independent [translocation of apoptosis-inducing factor (AIF) to the nucleus] signalling pathway. Analysis of upstream signalling events affected by resveratrol revealed that the activated caspase-8 triggered mitochondrial apoptotic events by inducing Bid cleavage without any alteration in the levels of Bax, Bcl-xL or Bcl2. The caspase-8 inhibitor or over-expression of crmA abrogated cell death induced by resveratrol and prevented processing of the downstream cascade. CONCLUSION: The results suggest that resveratrol causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of RA FLS.

Major aromatic VOC in the ambient air in the proximity of an urban landfill facility.

In this study, the environmental behavior of major aromatic VOC (including benzene, toluene, ethylbenzene and xylene, commonly called BTEX) in the ambient air was investigated from a mid-size municipal landfill site located in Dae Gu city, Korea in the winter of 2004. A series of field campaigns were conducted in the course of the study to cover eight different locations within and near this landfill site along with a number of VOC vent systems. The mean concentrations of different VOC species in ambient air fell in a comparable range of at or above a few ppb (e.g., the most abundant toluene approximately 10 ppb). An inspection of the VOC data sets at the studied LF sites also indicated that they are quite analogous to those typically found in other urban areas in terms of their absolute magnitude and relative pattern (e.g., the general dominance of toluene over the other species). In light of the fact that there is active ventilation of landfill gas (LFG: e.g., with their LFG concentrations above a few to a few tens of ppm) in the study area with no other distinct source processes, it can be concluded that the effects of the landfill processes may be as important as other point sources in maintaining VOC concentration levels in certain urban areas.

Effect of postnatal catch-up growth on blood pressure in children at 3 years of age.

Size at birth and early postnatal growth rates appear to be important determinants of cardiovascular diseases. We examined whether intrauterine growth restriction or the subsequent catch-up postnatal weight gain leads to higher blood pressure in early life to confirm that size at birth and early postnatal growth rates appear to be important determinants of blood pressure changes in early life. Of 407 children born between December 2001 and November 2002 in hospital based-birth cohorts, 102 were followed up at 3 years of age (24.2%) at Ewha Womans University Hospital in Seoul, Korea. At 3 years of age, those who had a low birth weight still belonged in the lower-weight group than the others. The subjects' systolic blood pressure was correlated with their current weight (r=0.41) and weight gain (r=0.39), but not with their birth weight. Those with a higher current weight and higher weight gain based on birth weight (conditional weight gain) had the highest blood pressure. Systolic blood pressure increased by 0.2 mm Hg for every 100-g increase in weight at 3 years and, independently, by 1.5 mm Hg for every 100-unit increase in conditional weight gain. This study suggests that birth weight is not directly associated with blood pressure, but accelerated growth, which occurs mostly in those born with a low birth weight, seems to affect blood pressure in early life.

A Case of Ectopic Paragonimiasis in a 17th Century Korean Mummy.

Archaeoparasitological studies on fossilized feces obtained from Joseon Dynasty (1392-1910 CE) mummies have provided invaluable data on the patterns of parasitic infection in pre-modern Korean societies. In our recent radiological investigation of a 17th century Joseon mummy discovered in Cheongdo (South Korea), we located a liver mass just below the diaphragm. Anatomical dissection confirmed the presence of a mass of unknown etiology. A subsequent parasitological examination of a sample of the mass revealed a large number of ancient Paragonimus sp. eggs, making the current report the first archaeoparasitological case of liver abscess caused by ectopic paragonimiasis.