Phase II study of a trastuzumab biosimilar in combination with paclitaxel for HER2-positive recurrent or metastatic urothelial carcinoma: KCSG GU18-18.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a widely explored therapeutic target in solid tumors. We evaluated the efficacy and safety of trastuzumab-pkrb, a biosimilar of trastuzumab, in combination with paclitaxel, in HER2-positive recurrent or metastatic urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled 27 patients; they were administered a loading dose of 8 mg/kg trastuzumab-pkrb on day 1, followed by 6 mg/kg and 175 mg/m2 paclitaxel on day 1 every 3 weeks, intravenously. All patients received six cycles of the combination treatment and continued to receive trastuzumab-pkrb maintenance until disease progression, unacceptable toxicity, or for up to 2 years. HER2 positivity (based on immunohistochemistry analysis) was determined according to the 2013 American Society of Clinical Oncology /College of American Pathologists HER2 testing guidelines. The primary endpoint was objective response rate (ORR); the secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Twenty-six patients were evaluated via primary endpoint analysis. The ORR was 48.1% (1 complete and 12 partial responses) and the duration of response was 6.9 months [95% confidence interval (CI) 4.4-9.3 months]. With a median follow-up of 10.5 months, the median PFS and OS were 8.4 months (95% CI 6.2-8.8 months) and 13.5 months (95% CI 9.8 months-not reached), respectively. The most common treatment-related adverse event (TRAE) of any grade was peripheral neuropathy (88.9%). The most common grade 3/4 TRAEs were neutropenia (25.9%), thrombocytopenia (7.4%), and anemia (7.4%). CONCLUSIONS: Trastuzumab-pkrb plus paclitaxel demonstrates promising efficacy with manageable toxicity profiles in patients with HER2-positive recurrent or metastatic UC.

Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG).

BACKGROUND: There is no clear consensus on the recommended second-line treatment for patients with metastatic pancreatic cancer who have disease progression following gemcitabine-based therapy. We retrospectively evaluated the clinical outcomes of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (FL) and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in patients who had failed on the first-line gemcitabine-based therapy. PATIENTS AND METHODS: From January 2015 to August 2019, 378 patients with MPC who had received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as second-line treatment across 11 institutions were included in this retrospective study. RESULTS: There were no significant differences in baseline characteristics between groups, except age and first-line regimens. With a median follow-up of 6 months, the median progression-free survival (PFS) was 3.7 months with nal-IRI/FL versus 4.6 months with FOLFIRINOX (P = 0.44). Median overall survival (OS) was 7.7 months with nal-IRI/FL versus 9.7 months with FOLFRINOX (P = 0.13). There was no significant difference in PFS and OS between the two regimens in the univariate and multivariate analyses. The subgroup analysis revealed that younger age (<70 years) was associated with better OS with FOLFIRINOX. In contrast, older age (≥70 years) was associated with better survival outcomes with nal-IRI/FL. Adverse events were manageable with both regimens; however, the incidence of grade 3 or higher neutropenia and peripheral neuropathy was higher in patients treated with FOLFIRINOX than with nal-IRI/FL. CONCLUSIONS: Second-line nal-IRI/FL and FOLFIRINOX showed similar effectiveness outcomes after progression following first-line gemcitabine-based therapy. Age could be the determining factor for choosing the appropriate second-line therapy.

Non-Markovian Exciton-Phonon Interactions in Core-Shell Colloidal Quantum Dots at Femtosecond Timescales.

We perform two-dimensional coherent spectroscopy on CdSe/CdZnS core-shell colloidal quantum dots at cryogenic temperatures. In the two-dimensional spectra, sidebands due to electronic coupling with CdSe lattice LO-phonon modes are observed to have evolutions deviating from the exponential dephasing expected from Markovian spectral diffusion, which is instantaneous and memoryless. Comparison to simulations provides evidence that LO-phonon coupling induces energy-gap fluctuations on the finite timescales of nuclear motion. The femtosecond resolution of our technique probes exciton dynamics directly on the timescales of phonon coupling in nanocrystals.

Influence of urban neighbourhood environment on physical activity and obesity-related diseases.

OBJECTIVES: The impact of characteristics of neighbourhood environment on physical activity and obesity-related diseases is still the subject of debate. This study aimed to explore the impact of urban neighbourhood environment on physical activity and obesity-related diseases. STUDY DESIGN: Cross-sectional study. METHODS: Individuals who participated in the 2009 national health-screening programme, submitted all necessary information, and had lived in Community 1 (Haengdang) or Community 2 (Ilsan) for at least 2 years (n = 16,178) were selected for inclusion in this study. Anthropometric measures were taken and physical activity was assessed using a short questionnaire. RESULTS: No significant difference in the trigger factors for walking, including the amount of neighbourhood park space, number of shopping malls, and distance between the community and shopping malls, was found between the two communities. However, Community 2 had a better street environment than Community 1. Participants who lived in Community 2 were more physically active [adjusted odds ratio (OR) 1.31, 95% confidence interval (CI) 1.16-1.48] and walked more regularly (adjusted OR 1.09, 95% CI 1.02-1.17) than participants who lived in Community 1, and were less likely to have abdominal obesity (adjusted OR 0.83, 95% CI 0.77-0.91), hypertension (adjusted OR 0.88, 95% CI 0.80-0.97) and diabetes (adjusted OR 0.86, 95% CI 0.75-0.99). However, the risk of dyslipidaemia, especially in terms of low-density lipoprotein cholesterol, was higher in Community 2. CONCLUSIONS: These results suggest that a walkable environment has a positive influence on hypertension and diabetes, and physical activity is the possible mechanism for this association. A walkable environment may function as an important tool for health promotion in urban areas.

Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population.

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis aimed to investigate the effect of antioxidant supplements on the primary and secondary prevention of cancer as reported by randomized controlled trials. METHODS: We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. RESULTS: Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96-1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97-1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83-1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06-2.17) in a subgroup meta-analysis of four trials. CONCLUSIONS: The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.

Efficacy of low-calorie, partial meal replacement diet plans on weight and abdominal fat in obese subjects with metabolic syndrome: a double-blind, randomised controlled trial of two diet plans - one high in protein and one nutritionally balanced.

BACKGROUND: Little is known about the relative efficacy of high-protein vs. conventional diet plans that include partial meal replacements on body fat loss in obese subjects with metabolic syndrome. OBJECTIVE: We aimed to evaluate the efficacy of two low-calorie diets with partial meal replacement plans-a high-protein plan (HP) and a nutritionally balanced conventional (C) plan-on reducing obesity in obese subjects with metabolic syndrome. DESIGN: In a 12-week, double-blind study, we randomised 75 participants to either the HP- or the C-plan group. We recorded key metrics at 0 and 12 weeks. RESULTS: The overall mean weight loss was 5 kg in the HP-plan group and 4.9 kg in the C-plan group (p = 0.72). Truncal fat mass decreased 1.6 kg in the HP-plan group (p < 0.05) and 1.5 kg in the C-plan group (p < 0.05), while whole body fat mass decreased 2.5 kg in the HP-plan group (p < 0.05) and 2.3 kg in the C-plan group (p < 0.05). Between-group losses did not differ significantly for truncal (p = 0.52) or whole body (p = 0.77) fat mass. Among subjects with > or = 70% dietary compliance, however, truncal and whole body fat mass decreased more in the HP-plan group (Delta 2.2 kg and Delta 3.5 kg respectively) than in the C-plan group (Delta 1.3 kg and Delta 2.3 [corrected] kg respectively) (p < 0.05). CONCLUSION: The HP- and C-plans had a similar effect on weight and abdominal fat reduction, but the HP-plan was more effective in reducing body fat among compliant subjects.

Pancreatic carcinoid tumor with obstructive pancreatitis: multislice helical CT appearance: case report.

Carcinoid tumor of the pancreas is rare. Moreover, obstructive pancreatitis secondary to a pancreatic carcinoid tumor is extremely rare. We report a case of pancreatic carcinoid tumor in a 50-year-old male who presented with pancreatitis. On multislice helical computed tomography, the main pancreatic duct was obstructed by a small round tumor, and the main pancreatic duct proximal to the tumor was dilated. The correlation between the main pancreatic duct and the tumor was well depicted on minimum intensity projection image. This is the first report of multislice helical computed tomorgraphic and minimum intensity projection image findings of a pancreatic carcinoid tumor presenting with pancreatitis.

Small cell carcinoma of the colon: barium study and CT findings.

Extrapulmonary small cell carcinoma is a rare neoplasm. It is an aggressive malignant tumour characterized by rapid local progression and early metastasis. We report a case of small cell carcinoma arising in the transverse colon in a 34-year-old man who presented with epigastric pain. On CT, a poorly enhancing bulky mass encircling the transverse colon with extensive regional lymph node metastases was observed. A segmental annular narrowing with thick interhaustral folds of the transverse colon was found by barium enema examination. This is the first report of barium study and CT findings of extrapulmonary small cell carcinoma of the colon.

Application of extended single-reaction multiplex polymerase chain reaction for toxin typing of Staphylococcus aureus isolates in South Korea.

The extended single-reaction multiplex PCR (esr-mPCR) developed in this study to detect staphylococcal enterotoxins (SEs), including SEA, SEB, SEC, SED, SEE, SEH, SEI, and SEJ, requires fewer sets of primers than other conventional multiplex PCRs and can be used to detect newly identified staphylococcal enterotoxins SEs more readily. Esr-mPCR analysis of 141 isolates of Staphylococcus aureus obtained from abattoir and livestock product samples revealed that 27 of the S. aureus isolates were toxigenic, and two were 2 multitoxigenic isolates. The most prevalent SE type was SEI followed by SEA and SEH. In addition, we investigated the clonal relatedness of toxigenic S. aureus isolates by arbitrarily primed PCR (AP-PCR). AP-PCR analysis of toxigenic S. aureus isolates revealed that the discriminatory power of AP-PCR was 9 (D=0.81), 8 (D=0.77), and 10 types (D=0.83) with primers AP1, ERIC2, and AP7, respectively. The combination of three each AP-PCR result could rearrange toxigenic S. aureus isolates into 10 types and five subtypes, with the D-value of 0.92. Interestingly, our data showed that toxigenic S. aureus isolates from different sources had different fingerprinting patterns although some of them carried the same types of SE genes. These data suggest that combinations of esr-mPCR and AP-PCR can provide a powerful approach for epidemiological investigation of toxigenic S. aureus isolates.

Three-dimensional reconstructed images using multidetector computed tomography in evaluation of the biliary tract.

The recent development of multidetector computed tomography (MDCT) and the parallel escalation in the capabilities of the workstation allow the use of high-quality multiplanar and three-dimensional reconstruction images. As a noninvasive technique, MDCT dedicated to the biliary tract represents an alternative to magnetic resonance cholangiography. The usefulness of three-dimensional reconstructed images using MDCT in evaluating biliary tract abnormality is illustrated.

Antimicrobial performance of alkaline ionic fluid (GC-100X) and its ability to remove Escherichia coli O157:H7 from the surface of tomatoes.

An efficacy test of GC-100X, a noncorrosive alkaline ionic fluid (pH 12) composed of free radicals and supplemented with xylitol, was carried out against six major foodborne pathogens-Staphylococcus aureus FRI 913, Salmonella enterica serovar Enteritidis ATCC 13076, S. enterica serovar Typhimurium DT104 Korean isolate, Vibrio parahaemolyticus ATCC 17803, Escherichia coli O157:H7 ATCC 43894, and Pseudomonas aeruginosa KCTC 1637-at three different temperatures (4, 25, and 36 degrees C) with or without organic load (2% yeast extract). Results revealed a more than 4-log10 (CFU/ml) reduction (1.0 x 10(4) CFU/ml reduction) against all pathogens reacted at 37 degrees C for 3 h in the absence of organic material. GC-100X solution diluted with an equal volume of distilled or standard hard water (300 ppm CaCO3) showed effective bactericidal activity, particularly against gram-negative bacteria. Washing efficacy of GC-100X solution was compared against E. coli O157:H7 on cherry tomato surfaces with those of a commercially used detergent and chlorine water (100 ppm). Viable cell counts of E. coli O157:H7 that had penetrated to the cores of tomatoes after sanitizing treatment revealed that GC-100X stock and its 5% diluted solutions had similar washing effects to 100-ppm chlorine water and were more effective than the other kitchen detergent. These results indicate that GC-100X has good bactericidal and sanitizing activities and is useful as a new sanitizer for food safety and kitchen hygiene.

Inhibitory activity of Bifidobacterium longum HY8001 against Vero cytotoxin of Escherichia coli O157:H7.

Vero cytotoxin (VT)-producing Escherichia coli (VTEC), such as E. coli O157:H7, are emerging foodborne pathogens worldwide. VTs are associated with hemorrhagic colitis and hemolytic uremic syndrome in humans. Attachment of the B subunit of VTs to its receptor, globotriaosylceramide (Gb3), at gut epithelium is the primary step and, consequently, the A subunit of VTs inhibits protein synthesis in the target cell. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, up-regulate Gb3 expression, increase sensitivity to VTs, and enhance VT action in developing disease. Currently, there is a growing interest in probiotics, given the increasing occurrence of antibiotic-resistant bacteria. In particular, much work on bifidobacteria among probiotics, regarded as microorganisms targeted for technological and therapeutic applications, has been performed. In Korea, the neutralizing effect of the culture supernatant of Bifidobacterium longum HY8001, Korean isolate, against the VTs from E. coli O157:H7 was found. Therefore, this study focused on the raveling of the inhibitory effect of B. longum HY8001 against VTs, through the interference B subunit of VTs and Gb3 interaction. Mice were inoculated intragastrically with B. longum HY8001 culture supernatant before and after challenge with E. coli O157:H7. Control mice were inoculated intragastrically only with E. coli O157:H7. Cytokine, TNF-alpha, and IL-1beta levels in sera and expression of their mRNA were decreased, and expression of Gb3 in renal tubular epithelial cells was reduced in mice treated with B. longum HY8001 culture supernatant. In competitive enzyme-linked immunosorbent assays (ELISAs), the culture supernatant of B. longum HY8001 primarily binds VTs to interfere the VTs with Gb3 interaction. These results suggest that soluble substance(s) in B. longum HY8001 culture supernatant may have inhibitory activity on the expression of Gb3, VT-Gb3 interaction, or both. Further study should be done to elucidate the property of soluble substances in B. longum HY8001 culture supernatant.

Location of the chronic subdural haematoma: role of the gravity and cranial morphology.

Chronic subdural haematoma (SDH) frequently originates from subdural hygroma (SDG). The cranial morphology can determine the location of SDG. Since SDG is the precursor of chronic SDH, the shapes of the cranium wall act an important role in location of chronic SDH. The authors tried to test this hypothesis. The computed tomographic scans or magnetic resonance images of 118 consecutive patients with chronic SDH were re-evaluated, and the symmetry of the cranium and location of the lesion were checked. The cranium was symmetrical in 55 patients (47%) and asymmetrical in 63 patients (53%). Chronic SDH was bilateral in 25 patients (21%) and unilateral in 93 patients (79%). It was more commonly bilateral in symmetrical craniums than in asymmetrical craniums (29.1% vs. 14.3%) (p = 0.0496). In 63 patients with asymmetric cranium, the chronic SDH was bilateral in nine patients, located on the opposite side of the flat side in 38 patients, and located on the same side of the flat side in 17 patients. This unequal distribution was statistically significant (p = 0.03). In four patients, the haematoma originated from the acute SDH located on the same side of the flat side. No reason could be found in the remaining 13 patients. Chronic SDH originating from SDG usually locates on the opposite to the flat side of the skull. The shape and posture of the cranium can predict the location of chronic SDH, as in the SDG.

The fate of traumatic subdural hygroma in serial computed tomographic scans.

We reviewed serial computed tomographic (CT) scans of 58 patients with traumatic subdural hygroma (SDG) to investigate its natural history. All were re-evaluated with a special reference to the size and density of SDG. Thirty-four patients (58.6%) were managed conservatively and 24 patients (41.4%) underwent surgery. The lesion was described as remained, reduced, resolved, enlarged and changed. Means of interval from injury to diagnosis and any changes in CT were calculated. SDGs were resolved in 12 (20.7%), reduced in 15 (25.9%), remained in 10 (17.2%), enlarged in 2 (3.4%), and changed into chronic subdural hematoma (CSDH) in 19 patients (32.8%). SDG was diagnosed at 11.6 days after the injury. It was enlarged at 25.5 days, remained at 46.0 days, reduced at 59.3 days, resolved at 107.5 days, and changed into CSDH at 101.5 days in average. SDGs were developed as delayed lesions, and changed sequentially. They enlarged for a while, then reduced in size. The final path of a SDG was either resolution or CSDH formation. Nearly half of SDGs was resolved or reduced within three months, however, 61.3% of unresolved or unreduced SDG became iso- or hyperdense CSDH. These results suggest that the unresolved SDG is the precursor of CSDH.

Location of the traumatic subdural hygroma: role of gravity and cranial morphology.

Traumatic subdural hygroma (TSH) is frequently bilateral and locates on the top of the head in a supine position. It suggests that the gravity and cranial posture act a certain role. The authors tried to test this hypothesis. The computed tomographic (CT) scans or magnetic resonance (MR) images of 86 consecutive patients with TSH were re-evaluated. The symmetry of the cranium, the posture of the head during the radiological examinations, and the location of the lesion were all checked. The cranium was symmetrical in 47 patients and asymmetrical in 39 patients. TSH was more commonly bilateral in patients with symmetrical cranium than those with asymmetrical cranium (77% vs 62%). The asymmetrical cranium tended to turn to the flat side. It was more frequently oblique in MR images, which has a long scanning time, than in CT (29% vs 18%). In 39 asymmetric craniums, TSH was bilateral and it was symmetrical in 14 cases. In the remaining 25 cases, TSH located opposite to the flat side in 18 cases. In seven patients with the same side TSHs, four patients had it on the side of atrophy, two on the opposite side of a mass lesion. The gravity and cranial posture can predict the location of TSH. TSH usually occurs at the least pressure in the cranium as a lesion of ex vacuo.

Origin of chronic subdural haematoma and relation to traumatic subdural lesions.

The origin of chronic subdural haematoma (CSDH) and the pathogenesis of subdural hygroma (SDG) are still controversial issues. These issues and relationships between these traumatic subdural lesions are discussed. The origin of CSDH is usually a SDG, although a few cases are caused by acute subdural haematomas (ASDH). Subdural hygroma is produced by separation of the dura-arachnoid interface, when there is sufficient subdural space. When the brain remains shrunken, the SDG remains unresolved. Any pathologic condition inducing cleavage of tissue within the dural border layer at the dura-arachnoid interface can induce proliferation of dural border cells with production of neomembrane. In-growth of new vessels will follow, especially along the outer membrane, then bleeding from these vessels occurs. These unresolved SDGs become CSDHs by repeated microhaemorrhage from the neomembrane. Although most victims with ASDH underwent surgery or died, some patients could be managed conservatively. Since the ASDH is usually absorbed within a few weeks, only a very few ASDHs become CSDHs, when there is a sufficient potential subdural space. Chronic subdural haematoma can arise from ASDH, but more commonly from SDG. Such transformation, or development of a new subdural lesion, is a function of the premorbid status and the dynamics of absorption and expansion.

The computed tomographic attenuation and the age of subdural hematomas.

The sequential change in density (attenuation coefficient) of subdural hematomas (SDHs) in computed tomography (CT) is important in understanding the pathogenesis and evolution of SDHs. We retrospectively investigated the age of SDHs by CT in 446 cases. We included 30 cases of chronic SDHs, in whom the density was directly measured in the CT. The density of acute (within 7 days) SDH was hyperdense in 98.6%, isodense in 1.1%, and hypodense in 0.3% of the cases. In subacute (8-22 days) SDHs, it was hypodense in 45.7%, isodense in 42.9%, and hyperdense in 11.4%. In chronic (over 22 days) SDHs, 86.7% was isodense and only 13.3% was hypodense. In hypodense SDHs, 64.0% was the subacute, and 73.2% of the isodense SDHs was the chronic one. The mean interval from injury to CT was 0.5 +/- 1.6 days in hyperdense SDHs, 20.9 +/- 20.7 days in hypodense SDHs, and 54.9 +/- 44.0 days in isodense SDHs. In 30 cases of chronic SDH, the average density was 38.0 +/- 6.9 Hounsfield number(H) in 20 approximately 30 days, 43.8 +/- 12.8 H in 31 approximately 60 days, 51.8 +/- 5.1 H in 61 approximately 90 days, and 44.2 +/- 8.3 H in over 90 days. The density of acute SDH is usually hyperdense. It becomes hypodense within 3 weeks. Then the density progressively increases by the repeated microhemorrhage, which is the mechanism of enlargement of chronic SDH. The density of chronic SDH increases with time up to 90 days, then decreases again after maturation of the neomembrane, which is the mechanism of spontaneous resolution.

Brain abscess from a ganglionic hemorrhage--a case report.

We present a unique case of a brain abscess that occurred secondary to a ganglionic hemorrhage in a 64-year-old man. This abscess appeared to be metastatic after septicemia. Aspiration with antibiotics eliminated this infection.