Surgical resection and orbital iodine-125 brachytherapy for orbital malignancy: a novel treatment for orbital lymphoma.

OBJECTIVES: Orbital lymphoma is one of the most common adult orbital malignancies, accounting for approximately 10% of all orbital tumors. This study aimed to analyze the effects of surgical resection and orbital iodine-125 brachytherapy implantation for orbital lymphoma. PATIENTS AND METHODS: This was a retrospective study. Clinical data of 10 patients were collected from October 2016 to November 2018 and followed up to March 2022. Patients underwent the primary surgery for maximal safe removal of the tumor. After a pathologic diagnosis of a primary orbital lymphoma was established, iodine-125 seed tubes were designed based on the tumor size and invasion range, and direct vision was placed into the nasolacrimal canal or/and under the orbital periosteum around the resection cavity during the secondary surgery. Then, follow-up data, including the general situation, ocular condition, and tumor recurrence, were recorded. RESULTS: Of the 10 patients, the pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (6 cases), small lymphocytic lymphoma (1 case), mantle cell lymphoma (2 cases), and diffuse large B-cell lymphoma (1 case). The number of seeds implanted ranged from 16 to 40. The follow-up period ranged between 40 and 65 months. All patients in this study were alive and well had tumors that were completely controlled. No tumor recurrences or metastases occurred. Three patients had dry eye syndrome and two patients had abnormal facial sensation. No patient had radiodermatitis involving the skin around the eye, and no patient had radiation-related ophthalmopathy. CONCLUSIONS: Based on preliminary observations, iodine-125 brachytherapy implantation appeared to be a reasonable alternative to external irradiation for orbital lymphoma.

Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

Iodine-125 interstitial brachytherapy for malignant lacrimal sac tumours: an innovative technique.

OBJECTIVES: Primary malignant tumours of the lacrimal sac are rare, surgery and radiotherapy may induce substantial side effects for patients. Here, this article reports an innovative technique of interstitial brachytherapy developed for the treatment of malignant lacrimal sac tumours. PATIENTS AND METHODS: Four patients (male 3, female 1), with an average age of 52.7 years (range 41-72 years), were individually diagnosed with squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma and lymphoma. All patients received Iodine-125 interstitial brachytherapy after surgical resection for malignant lacrimal sac tumours. Visual function examination (vision, intraocular tension, fundus photography, fluorescein angiography, and optical coherence tomography) and CT/MRI/PET-MRI were performed to look for signs of recurrent tumours or metastasis. RESULTS: Four patients were followed for an average of 28 months (range, 23-37 months). All patients were free from local disease. Their visual function was normal, and CT/MRI did not reveal any tumour recurrence. CONCLUSIONS: Iodine-125 interstitial brachytherapy can be used as an alternative to wide excision or exenteration of these tumours. There was good local control, reasonable maintenance of vision, and good cosmesis.

Central versus Distal Pancreatectomy for Benign or Low-Grade Malignant Lesions in the Pancreatic Neck and Proximal Body.

The purpose of this meta-analysis was to compare the clinical outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP). PubMed, Web of Knowledge, and Ovid's database were searched for studies published in English language between January 1990 and December 2018. A meta-analysis was performed to compare the clinical outcomes of CP versus DP. Nineteen trials with 1440 patients were analyzed. Although there were no significant differences in the rate of intraoperative blood transfusion between two groups, CP costs more operative time as well as had more intraoperative blood loss than DP. Furthermore, the overall complication rate, pancreatic fistula rate, and the clinically significant pancreatic fistula rate were significantly higher in the CP group. On the other hand, CP had a lower risk of endocrine (odds ratio: 0.17; 95% confidence interval: 0.10, 0.29; P < 0.05) and exocrine insufficiency (odds ratio: 0.22; 95% confidence interval: 0.10, 0.48; P < 0.05). CP was associated with a higher pancreatic fistula rate, and it should be performed in selected patients who need preservation of the pancreas, which is of utmost importance.

BURSECTOMY IN GASTRIC CANCER SURGERY: A META-ANALYSIS.

BACKGROUND: Bursectomy consists of surgically removing the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon during gastrectomy. However, there are little data to indicate whether bursectomy has a clinical benefit. OBJECTIVE: The objective of this study was to study the effect of bursectomy on complications, recurrence, and overall survival of patients with gastric cancer. METHODS: The publicly available literature published from January 2000 to July 2017 concerning gastrectomy with bursectomy and standard gastrectomy for gastric cancer was retrieved by searching the national and international online databases. Meta-analysis was performed after the data extraction process. RESULTS: Eight studies were finally included for a total of 1644 patients, of whom 644 underwent bursectomy and 1000 received standard gastrectomy without bursectomy. As shown by the meta-analysis results, there were no statistically significant differences in the presence of total post-operative complications (odds ratio [OR] = 1.06, 95% confidence interval [CI] [0.83-1.35], p = 0.63), overall recurrence (OR = 1.07, 95% CI [0.77-1.50], p = 0.68), 3-year overall survival (OR = 1.30, 95% CI [0.82-2.07], p = 0.26), and 5-year overall survival (OR = 0.91, 95% CI [0.66-1.27], p = 0.58). CONCLUSION: Although application of bursectomy in radical gastrectomy did not increase post-operative complications, it offered no benefit to control tumor recurrence or improve overall survival.

Bursectomy in gastric cancer surgery: a meta-analysis

Abstract Background Bursectomy consists of surgically removing the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon during gastrectomy. However, there are little data to indicate whether bursectomy has a clinical benefit. Objective The objective of this study was to study the effect of bursectomy on complications, recurrence, and overall survival of patients with gastric cancer. Methods The publicly available literature published from January 2000 to July 2017 concerning gastrectomy with bursectomy and standard gastrectomy for gastric cancer was retrieved by searching the national and international online databases. Meta-analysis was performed after the data extraction process. Results Eight studies were finally included for a total of 1644 patients, of whom 644 underwent bursectomy and 1000 received standard gastrectomy without bursectomy. As shown by the meta-analysis results, there were no statistically significant differences in the presence of total post-operative complications (odds ratio [OR] = 1.06, 95% confidence interval [CI] [0.83-1.35], p = 0.63), overall recurrence (OR = 1.07, 95% CI [0.77-1.50], p = 0.68), 3-year overall survival (OR = 1.30, 95% CI [0.82-2.07], p = 0.26), and 5-year overall survival (OR = 0.91, 95% CI [0.66-1.27], p = 0.58). Conclusion Although application of bursectomy in radical gastrectomy did not increase post-operative complications, it offered no benefit to control tumor recurrence or improve overall survival.

Metastatic retinoblastoma of the parotid and submandibular glands: a rare case report.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy occurring in children. It can metastasize to the regional lymph nodes, central nervous system and distant organs usually the bones and bone marrow and very rarely to the soft tissue. Here, we report a case of unilateral retinoblastoma in a 4-year-old girl accompanied by a large metastasis of the parotid and submandibular glands that developed about 6 months previously and gradually increased in size 5 months after enucleation of the left eye. CASE PRESENTATION: A 4-year-old girl with a history of unilateral retinoblastoma presented with a large, painful and worsening mass (about 20 × 23 cm) of the left side of the neck. Following surgery, the orbital tumour was completely resected, and the large tumour invasion range in the left side of the neck was not resected completely. Histopathological examination revealed retinoblastoma of the orbit and the parotid and submandibular glands. After chemotherapy and additional local radiotherapy on the parotid and submandibular glands, the tumour was inactive and stable. CONCLUSIONS: Delayed detection and inappropriate management contribute to poor outcomes. Fundus examinations, education regarding the early signs of RB, and optimization of the therapeutic strategy for RB may play important roles in ocular health.

Integrin-linked kinase inhibition attenuates permeability of the streptozotocin-induced diabetic rat retina.

Integrin-linked kinase (ILK), as a multi-functional regulator, has been associated with diabetic retinopathy (DR). In this study, we investigated whether inhibition of ILK could result in therapeutic effects. Diabetes mellitus's rats were induced by streptozotocin (STZ) injection. After 1 weeks induction, rats were injected intraperitoneally daily with ILK inhibitor, QLT0267, at 5 mg/kg. Then, the rats were examined by 4, 8, and 12 weeks after first STZ injection. We found that QLT0267 treatment could not only lower ILK level in retina at as early as 3 weeks after the onset of diabetes but also attenuate retina permeability, which was measured by Evan's blue. Maximum effect was found in 11 weeks treatment. Meanwhile, QLT0267 did not disturbed blood glucose concentration. Furthermore, QLT0267 inhibited Akt (Ser473) activation and reduced expression of HIF1α and VEGF which were evaluated by western blot, real time PCR, and immunohistochemistry. We conclude that ILK may be a new target for DR.

[Research on formaldehyde concentration detection system based on photo-elastic modulation].

There is a growing number of environmental pollution caused by excessive indoor formaldehyde, and in order to quickly and accurately quantify the concentration of formaldehyde gas in indoor air, a system for detecting the concentration of formaldehyde gas based on photo-elastic modulation was designed. It consists of the infrared light source, filters, elastic light modulator, and infrared detectors, and photo-elastic crystal refractive index of cyclical changes was controlled by elastic light modulator. Refractive index caused by the changes in the optical path provided a spectrum distribution function of the optical path difference. Optical path difference function of the system was derived through the HITRAN spectral database. Experiments were carried out using infrared light source combined with narrow band filters, and the transmittance of the center wavelength was more than 90%. Photo-elastic crystal is ZnSe crystal as photo-elastic light modulator, and the drive frequency of the system is 100 kHz. For three different environments at different locations, 10 groups of sample gas were collected for analysis, and the concentration of formaldehyde gas was detected using standard spectrometer and the system for comparing the test data. Experimental results show that when the concentration of formaldehyde gas is high, the system performance is good; When the concentration of formaldehyde gas is low, the signal-to-noise ratio of the system is decreased, and the detection accuracy is slightly reduced, but it still meets the design requirements.

Congenital orbital fibrosis associated with fibrosis of extraocular muscle.

Congenital orbital fibrosis is a non-familial, unilateral, distinct clinical entity, characterised by the presence of a diffusely infiltrating orbital mass and is extremely a rare disease. Congenital orbital fibrosis with combined fibrosis of extraocular muscles have not been reported previously. We treated an 8-year-old boy with the presence of a diffusely infiltrating orbital mass and fibrosis of extraocular muscles with secondary involvement of extraocular muscles. Clinical examination revealed left exotropia, hypotropia and fibrosis of extraocular muscle, an irregular, retrobulbar mass located within the orbit, incorporating the optic nerve, medial, superior, inferior and lateral rectus muscle. The CT, MRI and light microscopic studies confirmed the diagnosis. We performed exploration of the orbit, release and biopsy of scar tissue and strabismus surgery. Unlike other reported cases, our case was a progressive congenital disorder with combined fibrosis of extraocular muscle.

Primary malignant melanoma of the lacrimal sac.

Primary malignant melanoma of the lacrimal sac is extremely rare. It is usually diagnosed at an advanced stage after excision or biopsy of a tumour. We treated a 59-year-old man with tearing and bloody discharge from the right eye. Clinical examination revealed a firm, localised mass at the inner canthus consistent with a lacrimal sac swelling. Sac washout demonstrated obstruction to entry into the lacrimal sac with a reflux of blood-stained fluid. The pathological findings and the immunohistochemical studies showed a malignant melanoma of the lacrimal sac. We performed radical surgery and radiation therapy. Follow-up 4 months after surgery revealed no evidence of recurrence. Because this tumour often presents with symptoms similar to dacryocystitis and may masquerade as a chronic dacryocystitis, ophthalmologists should be aware of this disease entity when encountered with patients with epiphora and mass in the medial canthal area.

[Research on detecting trace formaldehyde gas by the multi-wavelengths characteristics method].

In order to overcome the slow speed of detecting trace formaldehyde in the sample gas, material consumption by chemical reaction, and the limitations of the sampling area in the detection of trace formaldehyde, a multi-wavelength characteristics method for getting the exact concentration of formaldehyde quickly was designed. According to the spectrum characteristics of formaldehyde and the main interfering gases the system chose multiple wavelengths with the minimum degree of coherence (the number of characteristic wavelengths were selected to be 3, 4 and 5), in conjunction with the corresponding groups of narrow-band filters. With the infrared light of the light source through the chamber windows and narrow-band filters, the infrared light was collected by the PCI-2TE-13 infrared detectors, and the concentration of formaldehyde in the sample gas was calculated by the characteristics spectrum absorption algorithm. In the experiments, the system analyzed and calculated the concentration of formaldehyde in four gas samples collected in the newly renovated house, building materials market, supermarkets and outdoor parks. Experimental results of the system and test results of ARCSpectro-AMIR infrared spectrometer were compared, the results show that test data above 10 mg x m(-3) were close to true value by the multi-wavelengths characteristics method, and the average error is less than 5%. So the system meets the requirements of practical applications, and it has the advantages of real-time detection, not poisoning so on.

Up-regulation of integrin-linked kinase in the streptozotocin-induced diabetic rat retina.

OBJECTIVES: This study investigated whether integrin-linked kinase (ILK) is involved in the pathogenesis of diabetic retinopathy, by analyzing the expression and activity of ILK in the retina from a streptozotocin (STZ)-induced rat model of diabetes. METHODS: ILK expression in the retina from both control and STZ-induced diabetic rats was measured by reverse transcription polymerase chain reaction, immunohistochemistry and Western blot analysis. The expressions of Akt and FOXO1A, the downstream molecules of ILK, were also examined. RESULTS: The present study showed that the STZ-induced diabetes was associated with the increase in the vascular permeability in the retina. This elevated vascular permeability increased with the progression of diabetic retinopathy. Meanwhile, the results also showed that the expression of ILK increased in protein and mRNA levels in the retina of STZ-induced diabetic rats. Immunohistochemistry showed that immunostaining of ILK was localized in the outer plexiform layer (OPL), the inner nuclear layer (INL), the inner plexiform layer (IPL), the ganglion cell layer (GCL) and the retinal microvasculature of rats. However, the expression of Akt was reduced in the retinas at 8 and 12 weeks and increased in the retinas at 4 weeks after induction of diabetes. Meanwhile, the expression of the FOXO1A protein increased in the retinas at 8 and 12 weeks and decreased in the retinas at 4 weeks after induction of diabetes. The FOXO1A immunostaining was also observed in the retinal microvasculature and in the OPL, INL, IPL and GCL of rat retinas. CONCLUSION: These results indicate that diabetes affects the expression of ILK in the retina. ILK may be involved in the diabetes-induced damage and/or alterations of neural and microvascular structures.

Epidermal growth factor receptor in cultured human retinal pigment epithelial cells.

BACKGROUND: Migration and proliferation of retinal pigment epithelial (RPE) cells play an important role in proliferative vitreoretinopathy. Epidermal growth factor receptor (EGFR) is a cell surface receptor with intrinsic tyrosine kinase activity. The engagement of the receptor by its ligand can induce intracellular mitogenic signal transduction pathways and stimulate proliferation, migration and differentiation of cells. This experiment aimed to investigate the activation and role of EGFR signal transduction pathway in proliferation of human RPE cells. METHODS: Cultured human RPE cells of the 3rd to 6th passages were studied by colorimetric assay for cellular growth and survival (MTT assay) to test the effects of EGF (0.1, 1, 10, 50, and 100 ng/ml) and fetal bovine serum (FBS) on proliferation of human RPE cells. An in vitro wound healing model was also set up, and the number of cells that had entered the denuded area was counted. The human RPE cells were cultured for 3 days with 0.1% FBS, 10% FBS, 10 ng/ml EGF + 0.1% FBS and a combination of EGF and 10% FBS, respectively. Immunohistochemical staining and in situ hybridization were used to observe the expressions of EGFR protein and mRNA, respectively. Activation of mitogen-activated protein kinase (MAPK) was detected by immunohistochemical method with specific antiphosphorylated extracellular signal-regulated kinase (ERK)1/2 antibody. RESULTS: EGF stimulated proliferation and migration of cultured human RPE cells in a concentration-dependent manner. The maximum of the proliferation rate of RPE cells was 81.8% with EGF at a concentration of 10-100 ng/ml of EGF in serum-free Dulbecco's modified essential medium (DMEM) and 122.7% at a concentration of 1-10 ng/ml of EGF in 5% FBS DMEM (p < 0.001); there was a significant difference between serum-free DMEM groups and 5% FBS DMEM groups. The maximum of the migration rate of the cells was 438.9% at a concentration of 10-100 ng/ml of EGF in 10% FBS DMEM, 147% with 10% FBS, and only 36% with EGF in 0.1% FBS at the concentration of 10 ng/ml (p < 0.001). EGF promoted the expression of EGFR protein and mRNA in RPE cells. FBS cooperated with EGF in the stimulation of EGFR expression, and it had a stronger effect in the process than EGF alone. After 3 days of incubation with EGF, phosphorylated ERK1/2 was detectable in the nucleus of RPE cells, whereas cells presented immunostaining positive for phosphorylated ERK1/2 in the cytoplasm before stimulation, indicating that EGF could induce MAPK nuclear translocation. CONCLUSION: EGF could induce EGF-EGFR-MAPK signal transduction pathway in human RPE cells in a concentration-dependent manner in vitro, which may play a key role in the activation of human RPE cell proliferation and migration.