OBJECTIVE: In order to investigate more accurate patterns of intrauterine growth in twin fetuses, we constructed the twin-specific growth curve based on gestational age in live-born non-anomalous infants. METHODS: 563 twin pairs, 1,126 infants delivered between January 1994 and October 1999 were comprised our study population. The newborns were grouped according to gestational age and the median, 10th, 50th, and 90th percentile birth weight for each gestational week were calculated. Curves were plotted for the general population and for each gender and parity and compared with previously reported singleton's growth curve. RESULTS: After 32 weeks gestation, birth weight of twins falls below that of singleton, so that by 38 weeks the 50th percentile for twins falls below the singleton 10th percentile. This difference was also present among all subgroups of twins, such as gender and parity. And the mean birth weight in male twin infant was heavier than in female twin infant throughout all gestational week. CONCLUSION: The pattern of growth in twin infants differed from those of singleton. We recommend twin-specific growth curve for clinical use in the management of twin gestations.
Birth Weight ; Female ; Fetus ; Gestational Age* ; Humans ; Infant ; Infant, Newborn ; Male ; Parity ; Pregnancy ; Twins*

To systematically review relevant literature on efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. In platinum pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 months vs. 7.4 months), a higher objective response rate (ORR; 21.1% vs. 11.4%, p=0.001), and a lower adverse event rate (60.9% vs. 90.2%). Three randomized controlled trials (RCTs) assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 months vs. 19.6 months) and the ORR (25% vs. 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In patients with metastatic castration-resistant prostate cancer, 2 RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively. Therefore, in metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.
Carcinoma, Renal Cell ; Cell Death ; Drug Therapy ; Everolimus ; Humans ; Immunotherapy ; Platinum ; Prostatic Neoplasms ; Treatment Outcome ; Urologic Neoplasms

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

Purpose: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure. Here, we developed genetically modified recombinant BCG (rBCG) strains which escape AMPs and evaluate the efficacy and effects of rBCG. Materials and Methods: We constructed rBCG strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. The efficacy of the Sic and dltA gene electroporation into BCG was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The internalization rates and anticancer effects of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA) was evaluated by the orthotopic bladder cancer mouse model. Results: The cycle quantification (Cq) values of rBCG-Sic (y=-4.8823x+13.645, R2=0.9996) and rBCG-dltA (y=-5.438x+11.641, R2=0.9995) were inverse correlations to the amount of Sic and dltA genes dose dependently. The mean introduction proportions of Sic and dltA genes into BCG by electroporation were 22.2%, 27.5% and showed constant efficacy. In the orthotopic bladder cancer mouse model, the relative internalization number of rBCG-Sic, and rBCG-dltA into bladder cell in mouse bladder were higher than that of BCG and the tumor volume at rBCG-Sic were lower than at BCG and rBCG-dltA at 11, 14 and 18 days. Conclusions Our results showed that constructed rBCG-Sic and rBCG-dltA by electroporation and the rBCG-Sic and rBCG-dltA can effectively escape BCG-stimulated AMPs, and significantly improved immunotherapeutic tools to treat bladder cancer in orthotopic bladder cancer mouse model.

PURPOSE: The purpose of this study was to evaluate the usefulness of FLAIR(Fluid Attenuated InversionRecovery) MR imaging in childhood adrenoleukodystrophy by comparing with those of T2-weighted FSE imaging, and tocorrelate MRI finidings with clinical manifestations. MATERIALS AND METHODS: Axial FLAIR images(TR/TE/TI=10004/123/2200) and T2-weighted FSE images(TR/TE=4000/104) of brain in six male patients(age range :6-17 years, mean age : 10.2 years) with biochemically confirmed adrenoleukodystrophy were compared visually by tworadiologists for detection, conspicuity, and the extent of lesion. Quantitatively, we compared lesion/CSFcontrast, lesion/CSF contrast to noise ratio(CNR), lesion/white matter(WM) contrast, and lesion/WM CNR betweenFLAIR and T2 weighted image. We correlated MR findings with clinical manifestations of neurologic symptoms andevaluated whether MRI could detect white matter lesions in neurologically asymptomatic patients. RESULTS: Visualdetection of lesions was better with FLAIR images in 2 of the 6 cases and it was equal in the remainders. Visualconspicuity and detection of the extent of lesion were superior on FLAIR images than T2-weighted images in all 6cases. In the quantitative assessment of lesions, FLAIR was superior to T2-weighted image for lesion/CSF contrastand lesion/CSF CNR, but was inferior to T2 weighted image for lesion/WM contrast and lesion/WM CNR. In one case,FLAIR images distinguished the portion of encephalomalacic change from lesions. MR findings ofadrenoleukodystrophy were correlated with clinical manifestations in symptomatic 4 cases, and also detected whitematter lesions in asymptomatic 2 cases. CONCLUSION: MR imaging with FLAIR sequence provided images that wereequal or superior to T2-weighted images in the evaluation of childhood adrenoleukodystrophy. MRI findings werewell correlated with clinical manifestations and could detect white matter lesions in neurologically asymptomaticadrenoleukodystrophy patients.
Adrenoleukodystrophy* ; Brain ; Humans ; Magnetic Resonance Imaging* ; Male ; Neurologic Manifestations ; Noise

BACKGROUND AND OBJECTIVES: Although human mesenchymal stem cell (hMSC) transplantation has been known to improve ventricular function, the potential proarrhythmic effects have not yet been studied. MATERIALS AND METHODS: We monitored the heart rhythm of 6 dogs for 4 weeks after transplantation of hMSC (1x10(7), epicardial injection) (hMSC group) and in 5 Sham dogs after the injection of the vehicle alone. Cardiac sympathetic nerve sprouting {nerve growth factor (NGF)-beta; tyrosine hydroxylase (TH)} and gap junction expression {connexin (Cx) 43} were evaluated in 10 dogs (5 hMSC and 5 Sham) that survived longer than 4 weeks. RESULTS: The hMSC group expressed higher levels of NGF-beta messenger ribonucleic acid (mRNA) (56.0+/-66.8 fold; p<0.01) with TH+ sympathetic nerves (0.51+/-0.40 vs. 0.15+/-0.13% area; p<0.03) than the Sham control. In contrast, the hMSC group expressed lower levels of Cx43 mRNA (0.59+/-0.29 fold, p<0.001) and Cx43+ (1.64+/-1.79 vs. 2.12+/-1.07% area, p<0.001) than the Sham control. The incidences of ventricular fibrillation were 33.3% and 0% in the hMSC group and Sham control, respectively. One of the dogs with ventricular fibrillation (VF) in the hMSC group died suddenly. CONCLUSION: hMSC transplantation may be proarrhythmic since NGF-beta expression increased with cardiac sympathetic hyperinnervation and the expression of Cx43 and the gap junction decreased.
Animals ; Connexin 43 ; Dogs ; Gap Junctions ; Heart ; Humans ; Incidence ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Nerve Growth Factor ; RNA ; RNA, Messenger ; Salicylamides ; Tachycardia, Ventricular ; Transplants ; Tyrosine 3-Monooxygenase ; Ventricular Fibrillation ; Ventricular Function

PURPOSE: Laparoscopic gastric wedge resection is a standard treatment for removing gastric submucosal tumors (SMTs). So far, however, there have been few reports of single-incision laparoscopic intragastric wedge resection. Our aim was to describe this procedure and our experience with it. METHODS: From January 2010 to December 2013, a total of 21 consecutive patients with gastric SMTs underwent single-incision intragastric resection at our institution. Their clinicopathologic data were analyzed retrospectively. RESULTS: The patients consisted of nine men and 12 women with a mean age of 51.9 +/- 12.9 years (22-69 years). Their mean body mass index was 22.6 +/- 2.0 kg/m2. Mean tumor size was 2.4 +/- 0.7 cm, with the following anatomic distribution: esophagogastric junction in three patients, fundus in twelve, upper body in three, and lower body in two. Mean operating time was 68.6 +/- 12.0 minutes. There were no conversions to open surgery and no major intraoperative complications. Time to resumption of water intake was 1.4 +/- 0.5 days. Mean hospital stay was 4.9 +/- 1.7 days. There were no recurrences or deaths during the mean 19-month follow-up. CONCLUSION: Single-incision intragastric wedge resection is a feasible and safe procedure. It is especially efficient for treating small endophytic gastric SMTs located on the upper and mid portion of the stomach.
Body Mass Index ; Drinking ; Esophagogastric Junction ; Female ; Follow-Up Studies ; Gastrectomy ; Gastric Mucosa ; Gastrointestinal Stromal Tumors ; Humans ; Intraoperative Complications ; Laparoscopy ; Length of Stay ; Male ; Recurrence ; Retrospective Studies ; Stomach ; Stomach Neoplasms

PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of CT and MR virtual colonoscopy using an experimental model of colonic polyposis. MATERIALS AND METHODS: Eleven pig colons ranging from 15 to 20cm in length were cleansed and a total of 99 variable sized polyps ranging from 3 to 15mm in diameter were created. The polyps were divided into three groups according to size: <5mm(n=23), 5-9mm(n=44), and ?10mm(n=32) in diameter. Each specimen was scanned using spiral CT and MRI. Each CT and MR virtual colonoscopy was independently evaluated by two radiologists blinded to the location, size and numbers of polyps, but aware that polyps were present. Interobserver agreement regarding the detection rate of the polyps during the two types of virtual colonoscopy was measured and the diagnostic accuracy of CT and MR virtual colonoscopy was compared. Results: In both CT and MR virtual colonoscopy, the detection rates determined by the two radiologists coincided in all three groups(p<0.05). The detection rates of polyps less than 5mm, between 5 and 9mm, and 10mm or larger in diameter were 74%(17/23), 89%(39/44), and 100%(32/32), respectively, in CT colonoscopy, and 61%(14/23), 89%(39/44), and 100%(32/32), respectively in MR colonoscopy. In polyps 5mm or larger, the results of the two types of virtual colonscopy coincided but in those less than 5mm in diameter, the results of MR virtual colonoscopy were slightly inferior to those of CT colonoscopy. Conclusion: Both CT and MR virtual colonoscopy provide high detection rates of colonic polyps 5mm or larger in diameter and these techniques can therefore be used to diagnose colonic mass lesions.
Colon ; Colonic Polyps ; Colonography, Computed Tomographic* ; Colonoscopy ; Magnetic Resonance Imaging ; Models, Theoretical ; Polyps* ; Tomography, Spiral Computed

PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of CT and MR virtual colonoscopy using an experimental model of colonic polyposis. MATERIALS AND METHODS: Eleven pig colons ranging from 15 to 20cm in length were cleansed and a total of 99 variable sized polyps ranging from 3 to 15mm in diameter were created. The polyps were divided into three groups according to size: <5mm(n=23), 5-9mm(n=44), and ?10mm(n=32) in diameter. Each specimen was scanned using spiral CT and MRI. Each CT and MR virtual colonoscopy was independently evaluated by two radiologists blinded to the location, size and numbers of polyps, but aware that polyps were present. Interobserver agreement regarding the detection rate of the polyps during the two types of virtual colonoscopy was measured and the diagnostic accuracy of CT and MR virtual colonoscopy was compared. Results: In both CT and MR virtual colonoscopy, the detection rates determined by the two radiologists coincided in all three groups(p<0.05). The detection rates of polyps less than 5mm, between 5 and 9mm, and 10mm or larger in diameter were 74%(17/23), 89%(39/44), and 100%(32/32), respectively, in CT colonoscopy, and 61%(14/23), 89%(39/44), and 100%(32/32), respectively in MR colonoscopy. In polyps 5mm or larger, the results of the two types of virtual colonscopy coincided but in those less than 5mm in diameter, the results of MR virtual colonoscopy were slightly inferior to those of CT colonoscopy. Conclusion: Both CT and MR virtual colonoscopy provide high detection rates of colonic polyps 5mm or larger in diameter and these techniques can therefore be used to diagnose colonic mass lesions.
Colon ; Colonic Polyps ; Colonography, Computed Tomographic* ; Colonoscopy ; Magnetic Resonance Imaging ; Models, Theoretical ; Polyps* ; Tomography, Spiral Computed

Dieulafoy's lesion is an uncommon but important cause of massive upper gastrointestinal bleeding. The lesion usually occurs in the lesser curvature of the stomach within 6 cm of the gastroesophageal junction but extragastric locations of Dieulafoy's lesion are rare. In this study, diagnosis of Dieulafoy's lesion was frequently made by endoscopy instead of surgery. Hemostasis was achieved by endoscopic treatment in more than 90% of patients. We report the successful application of endoscopic hemoclipping for treatment of active bleeding from Dieulafoy's lesion in the ampulla of Vater of the duodenum.
Ampulla of Vater* ; Diagnosis ; Duodenum ; Endoscopy ; Esophagogastric Junction ; Hemorrhage ; Hemostasis ; Humans ; Stomach