To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target ...volume (CTV) of this region could be modified in high-risk subsets.
Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting.
A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes.
According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.
Summary Background Progress in composite tissue allotransplantation could provide a new treatment for patients with severe facial disfigurements. We did a partial facial allotransplantation in 2006, ...and report here the 2 year follow-up of the patient. Methods The recipient, a 30-year-old man from China, had his face severely injured by a bear in October, 2004. Allograft composite tissue transplantation was done in April, 2006, after careful systemic preparation. The surgery included anastomosis of the right mandibular artery and anterior facial vein, whole repair of total nose, upper lip, parotid gland, front wall of the maxillary sinus, part of the infraorbital wall, and zygomatic bone. Facial nerve anastomosis was done during the surgery. Quadruple immunomodulatory therapy was used, containing tacrolimus, mycophenolate mofetil, corticosteroids, and humanised IL-2 receptor monoclonal antibody. Follow-up included T lymphocyte subgroups in peripheral blood, pathological and immunohistochemical examinations, functional progress, and psychological support. Findings Composite tissue flap survived well. There were three acute rejection episodes at 3, 5, and 17 months after transplantation, but these were controlled by adjustment of the tacrolimus dose or the application of methylprednisolone pulse therapy. Hepatic and renal functions were normal, and there was no infection. The patient developed hyperglycaemia on day 3 after transplantation, which was controlled by medication. Interpretation Facial transplantation could be successful in the short term, but the procedure was not without complications. However, promising results could mean that this procedure might be an option for long-term restoration of severe facial disfigurement. Funding New Clinical Technique Foundation of Xijing Hospital.
Objective We investigated the effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) on new bone formation during rapid-rate mandibular distraction osteogenesis. We also explored the ...feasibility of using local BMP-2 gene therapy to compensate for bad callus formation caused by a rapid distraction rate. Study design Bone marrow mesenchymal stem cells (MSCs) from Japanese rabbits were transfected with adenovirus (adv)–BMP-2. The right mandibles of the rabbits were distracted after corticotomy. The distraction rate in group A was 0.8 mm/d. The distraction rate in group B was 2.4 mm/d, and the distraction gap was injected with adv- lacZ –transfected bone marrow MSCs. The distraction rate in group C was 2.4 mm/d, and the distraction gap was injected with adv–BMP-2–transfected bone marrow MSCs. New generation bone tissue in the distraction gap was analyzed by plain radiograph examinations, microfocus computerized tomography (micro-CT) examinations, and biomechanical tests at weeks 2, 4, and 8 of the consolidation period. Results Radiographic and micro-CT examinations showed a better bone quality in group C compared with group A at weeks 2 and 4 of the consolidation period. There was no obvious new bone formation in group B. The trabecular parameters (trabecular thickness, trabecular number, volumetric bone mineral density at tissue, and bone volume fraction) were significantly higher in group C than in group A at weeks 2 and 4. At week 8, no significant difference were detected for all parameters except trabecular number between groups A and C. All biomechanical stress parameters were significantly higher in group C than in group A at week 4, and only peak stress was significantly different at week 8. Conclusions Gene therapy using rhBMP-2–modified MSCs promoted new bone formation during mandibular distraction osteogenesis, and effectively compensated for the detrimental effect of rapid distraction rate on new bone formation.
To describe the natural course of punctate inner choroidopathy (PIC) using spectral-domain optical coherence tomography (SD-OCT).
Prospective observational case series.
Forty-two consecutive patients ...(60 eyes) with PIC with at least 3 months of follow-up.
Serial SD-OCT images were obtained from both eyes of each participant at each visit.
The morphologic characteristics of each stage of PIC lesions observed by SD-OCT.
Continued stage progression of PIC lesions was observed in 27 eyes (45%), among which choroidal thickness changes were observed in 8 eyes (30%). Stage I lesion showed a normal appearance or slight irregularities in the outer nuclear layer. Stage II lesion appeared as a focal elevation of the retinal pigment epithelium (RPE) with corresponding disruption of the inner and outer segments of the photoreceptor interface. Stage III lesion broke through the RPE, forming a hump-shaped chorioretinal nodule with moderate reflectivity beneath the outer plexiform layer (OPL), generally with subsequent disruption of Bruch's membrane. Nodules occasionally invaded the inner retina, causing segmental retinal phlebitis in 2 eyes. Stage IV lesion regressed in a retrograde manner with tissue loss from the photoreceptor layer and inner choroid, finally leaving a V-shaped hernia of the OPL and inner retina into the choroid. Stage V lesion gradually eliminated the photoreceptors around the lesion; this process was accompanied by RPE proliferation at multiple levels, which reduced retinal herniation. Parafoveal stage V lesions caused late occult macular atrophy in 4 eyes. Choroidal thickness increased throughout the active phase and reached a peak at stage III; this parameter then significantly decreased at stage IV and gradually reached a minimum that was lower than the initial value at stage I.
Punctate inner choroidopathy is a chorioretinitis rather than an inner choroidopathy. Spectral-domain OCT characterized a 5-stage evolution of PIC lesions: choroidal infiltration, formation of sub-RPE nodules, and then chorioretinal nodules, regression, and retinal herniation.
Abstract Background Central lymph node (CLN) metastasis in papillary thyroid carcinoma (PTC) is common and being able to predict CLN metastasis helps surgeons determine individualized therapy. ...However, the relationship between contralateral CLN metastasis and the total number of positive lymph nodes (LNs) in the combined prelaryngeal and pretracheal region remains unclear. This study aimed to investigate whether the total number of positive LNs in the combined prelaryngeal and pretracheal region has clinical significance as a predictor for contralateral CLN metastasis. Methods We prospectively enrolled 153 consecutive patients with unifocal PTC >1.0 cm without ultrasonographic evidence of nodal metastasis who underwent total thyroidectomy and prophylactic bilateral CLN dissection from July 2011–May 2013. Patients were divided into three groups according to the total number of positive LNs in the combined prelaryngeal and pretracheal region. Results Rates of metastasis to ipsilateral and contralateral central compartments in PTC >1.0 cm were 84.3% and 24.2%, respectively. Multivariate analysis showed that ≥3 positive LNs in the combined prelaryngeal and pretracheal region were an independent predictive factor of contralateral CLN metastasis ( P < 0.001; odds ratio, 8.585). After a mean follow-up of 24.1 mo, none of these patients had a recurrence in the central or lateral compartment. Conclusions Occult metastasis is highly prevalent in the ipsilateral central neck of patients with PTC >1.0 cm, and the total number of prelaryngeal and pretracheal LNs metastases may be a useful indicator to predict contralateral CLN metastasis in patients with unifocal PTC.
Background:
Colorectal cancer (CRC) is a kind of gastrointestinal tumor with serious high morbidity and mortality. Several reports have implicated the disorder of RNA-binding proteins (RBPs) in ...plenty of tumors, associating it to tumorigenesis and disease progression. The study is intended to construct novel prognostic biomarkers associated with CRC patients.
Methods:
Data of gene expression was acquired from the TCGA database, prognosis-related genes were selected. Besides, we analyzed GO and KEGG pathways. Univariate and multivariate Cox analyses were performed to generate a prognostic-related gene signature, which was evaluated by the Kaplan-Meier (K-M) and the Receiver Operating Characteristic (ROC) curve. The independent prognostic factor was established by survival analysis. GSE38832 dataset was used to validate the signature. Finally, expression of 8 genes was further confirmed by qRT-PCR in SW480 and SW620 cell lines.
Results:
We obtained 224 differentially expressed RBPS in total, of which 78 were downregulated and 146 were upregulated. Univariate COX analysis was conducted in the TCGA cohort to select 13 RBPs with P < 0.005, stepwise multivariate COX regression analysis was used to construct an 8—RBP signature (TERT, PPARGC1A, BRCA1, CELF4, TDRD7, LUZP4, PNLDC1, ZC3H12C). Based on the model, systematic analysis illustrated that a high risk score was obviously connected to a poor prognosis. The prognostic value of the risk score was validated in GSE38832 dataset, indicating that the risk model was accurate and effective. The prognostic signature-based risk score was identified as an independent prognostic indicator for CRC. The expression results of qRT-PCR were consistent with the results of differential expression analysis.
Conclusions:
The eight-RBP signature can predict the survival of CRC patients and potentially act as CRC prognostic biomarker.
Pulmonary arterial hypertension (PAH) is a progressive disorder that affects both pulmonary vasculature and the heart. The response of the right ventricle (RV) to the increased afterload is an ...important determinant of the PAH final outcome. Galectin-3 (Gal-3), a novel biomarker in left cardiac remodeling, takes part in multiple pathophysiological processes including the inflammation, fibrosis, immunity, and oxidative stress. The levels of Gal-3 are elevated in PAH patients, although the exact mechanisms underlie the PAH-induced right ventricular structural changes remain unclear. Our results showed that the serum Gal-3 and NADPH oxidase 4 (Nox4) levels were significantly elevated and correlated in 26 human PAH patients when compared with 14 age- and sex-matched healthy controls. In the monocrotaline-induced PAH rat models of right ventricular hypertrophy and fibrosis, the Gal-3 and Nox4 expressions were both significantly upregulated compared with the controls. Moreover, the Gal-3 positive areas were co-localized with the collagen III-specific staining and the Gal-3 and Nox4 were partly co-localized in the intercellular area. The exogenous Gal-3 recombinant protein stimulated the proliferation, differentiation, collagen deposition, and Nox4 expression of cardiac fibroblasts. These simulations were blocked by the Gal-3 knockdown. The profibrotic effects of transforming growth factor-β1 (TGF-β1) on the cardiac fibroblasts were partially mediated by the Gal-3. Subsequently, our results showed that Gal-3 mediated the TGF-β1-induced cardiac fibrotic process through interacting with the Nox4 and Nox4-derived oxidative stress. Therefore, Gal-3 plays an important role in the PAH-induced right ventricular remodeling through interacting with the Nox4 and Nox4-derived oxidative stress. Gal-3 may become a RV-specific diagnostic and therapeutic target for clinics.
This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma ...(NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns.
A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy.
The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surrounding the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS.
Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients.
Background After pulsed dye laser (PDL) treatment, facial lateral port-wine stains (PWS) clear quicker and more completely than central PWS do. Objective We sought to investigate whether the ...difference in the efficacy of the treatment between central and lateral facial PWS was related to different histologic manifestations. Method Thirteen patients with PWS had biopsies and underwent PDL treatments in both central and lateral areas of the face. The hypothesis was tested by correlating the PWS response to PDL with the depth and diameter of the PWS vessels. The clinical efficacy was assessed by chromameter 2 months after the final PDL treatment, whereas diameter and depth of PWS vessels were measured in biopsy specimens. Results All patients were treated on central and lateral facial sites. The chromameter evaluation showed that the average blanching rate was 34.01% and 8.68% for lateral and central facial sites, respectively ( P < .05), which suggests a better response to PDL treatment in the lateral than in the central area. Histologic manifestations showed that vessels in the lateral regions were primarily located in the papillary dermis, whereas in the central regions they were extensively distributed from the dermis into the subcutaneous tissue. Limitations The small number of cases included in this study and the lack of follow-up longer than 2 months constitute limitations. Conclusion Lateral facial PWS respond better to PDL than PWS located in the central face. Differences in vessel location and diameter may be responsible for the variations in PWS response to PDL.
Abstract Background Understanding how socioeconomic events influence cause-specific mortality is essential for optimizing disease-control strategies. We characterized long-term trends in ...cause-specific mortality in a stable population from a very large urban centre. Methods We derived population data from 1974 to 2015 on vital status, demographics and causes of death from the death registration system in Yangpu District, Shanghai, China. We examined temporal trends in mortality and assessed the effects of age, period and birth cohort. Results Over 41 879 864 person-years of follow-up, we analyzed 290 332 deaths: 3.80% from communicable conditions (group 1), 86.50% from noncommunicable diseases (group 2), and 5.56% from injuries (group 3). Age-standardized mortality decreased after 1988 for group 1 (average annual percentage change AAPC −6.7, 95% confidence interval CI −9.3 to −4.1), after 1995 for group 2 (AAPC −2.9, 95% CI −3.5 to −2.3), and after 1994 for group 3 (AAPC −5.4, 95% CI −6.3 to −4.5), after improvements in public health and clinical service infrastructure and the removal of polluting industries during the 1980s. We observed increased mortality from group 2 and group 3 causes in those born between 1955 and 1965, a period that included the Great Chinese Famine. Cause-specific mortality risks increased in those born after 1949 for cancer and diabetes only. Interpretation Birth cohorts exposed to extreme starvation in early life had increased premature cause-specific mortality in later life. Decreased cause-specific mortality followed improvements in public health, medical infrastructure and pollution control, but not for cancer or diabetes, likely because of exposure to new risk factors.
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