Development a survival prediction model for patients with Paget disease of the breast based on the SEER database

Background:We explored the risk factors that affect the prognosis of patients with Paget disease of the breast(PD)and constructed a survival prediction model.Methods:The data of PD patients from 2004 to 2014 were collected through the SEER database.The factors affecting the prognosis of PD patients were analysed by a single factor,and the prediction model of the independent risk factor transformation model diagram that affected their 1-,3-,and 5-year survival rates was screened by multivariate Cox proportional hazard regression analysis coefficients.The consistency index was used to evaluate its predictive value,and its predictive performance was tested by the 1000 bootstrap method.Then,the calibration curve was used to verify the predictive performance of the model,and the receiver operating characteristic curve and decision curve analysis were used to assess the sensitivity and practicability of the model compared to the American Cancer Commission staging(AJCC)staging system.Results:The consistency index of the model was 0.795(95%confidence interval 0.773–0.818).The calibration curve shows good consistency,while the receiver operating characteristic curve shows the sensitivity of the model to predict the survival rate of PD at 1,3,and 5 years.Decision curve analysis confirmed that the nomogram can predict the survival rate of PD patients at 1,3,and 5 years instead of the traditional AJCC system.Conclusion:Regarding the independent prognostic factors of age,marital status,AJCC classification,surgery,radiotherapy,chemotherapy and marital status conversion in PD patients,the nomogram established in sequence has higher accuracy and clinical value than the traditional AJCC system.

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The Object of the Study: The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases. The Content: The content of this research paper includes a description of the patient, an analysis of the clinical picture, diagnostic methods and therapeutic interventions used, a report of the following disease, and the result of the presented case. The Result of the Research Work: The result of the research work is the analysis of a clinical case with two different tumors, where such a combination of tumors is rarely described in the literature. Moreover, no large specific sample with this combination of diseases is available. Patient Characteristics: The given case report describes a patient of the Palliative Care Unit of the Gerontology Clinic with a primary diagnosis of C20-rectal adenocarcinoma in the background of the anal canal, perineal skin Paget’s disease, stage IV. The presented complications of the patient’s primary diagnosis are multiple metastases in the liver;status post palliative chemotherapy;hepatomegaly;metastases to abdominal lymph nodes, inguinal lymph nodes;metastases at Th12, L4 level;pain syndrome. The presented above combination of diagnosed diseases is very rare. Applied Diagnostics: In October 2021, it was performed diagnostic manipulation: biopsy and the pathologist have provided a microscopic description. The first tissue fragment had a pronounced electrothermal lesion and the epithelial structures were not valuable. The second skin tissue fragment was covered with hyperplastic and acanthotic epithelium;its basal and middle layers contained multiple large cells proliferates extending into the medial epidermis, and the cytoplasm of these cells reacted positively with PAS (Periodic Acid Schiff reaction). It needs to be noted that the patient had previously had several years of biopsies from the perineal and anal epidermis, where Paget’s disease had also been diagnosed. The performed immunohistochemistry showed these cells to be CK20 positive, CK7 rare positive and p16 negative. The following pathohistological findings were made: morphological and immunohistochemical picture is consistent with Paget’s disease. According to the ICD-10, the patient was diagnosed with C51 malignant neoplasm of the female external genitalia. Using imaging diagnostics, it became clear that the patient’s rectal adenocarcinoma had progressed to metastatic stage with distant liver metastases in the background of anal canal, perineal skin Paget’s disease. Therapeutic Plan of the Patient: Based on the patient’s main diagnoses, the complications of the principal diagnosis, the patient’s overall severe condition, pain syndrome, age and comorbidities, palliative chemotherapy was approved as a therapeutic option in council of doctors. Monitoring and Outcome of the Patient: The patient’s general condition was becoming worse over time, and she was diagnosed with exitus latalis in December 2022. At that time, the patient was discharged from hospital and was on palliative care at home under the control of her family physician.

Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Total knee arthroplasty in patients with Paget's disease of bone: A systematic review

AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was performed. Four studies with a total of 54 TKAs were included for analysis. Functional outcomes, pain scores, complications and revision rates were assessed. The mean age was 72.0 years and the mean follow-up was 7.5 years.RESULTS All studies reported significant improvement in knee function and pain scores following TKA. There were 2 cases of aseptic loosening, with one patient requiring revision of the femoral component 10 years after the index procedure. Malalignment, bone loss, soft tissue contractures were the most commonly reported intraoperative challenges. There were five cases(9%) that were complicated by intra-operative patellar tendon avulsion.CONCLUSION The findings support the use of TKA in patients with PDB. The post-operative functional outcomes are largely similar to other patients, however there are specific perioperative challenges that have been highlighted, in particular the high risk for patellar tendon avulsion.

Total hip arthroplasty in patients with Paget's disease of bone: A systematic review

AIM To investigate the clinical and functional outcomes following total hip arthroplasty(THA) in patients with Paget's disease.METHODS We carried out a systematic review of the literature to determine the functional outcome, complications and revision rates of THA in patients with Paget's disease. Eight studies involving 358 hips were reviewed. The mean age was 70.4 years and follow-up was 8.3 years. There were 247 cemented THAs(69%), 105 uncemented THAs(29%) and 6 hybrid THAs(2%). RESULTS All studies reported significant improvement in hip function following THA. There were 19 cases of aseptic loosening(5%) at a mean of 8.6 years. Three cases occurred in the uncemented cohort(3%) at a mean of 15.3 years and 16 cases developed in the cemented group(6%) at a mean of 7.5 years(P = 0.2052). There were 27 revisions in the 358 cases(8%) occurring at a mean of 7 years. Six revisions occurred in the uncemented cohort(6%) at a mean of 8.6 years and 21 in the cemented cohort(9%) at a mean of 6.5 years(P = 0.5117). CONCLUSION The findings support the use of THA in patients with Paget's disease hip arthropathy. The post-operative functional outcome is largely similar to other patients; however, the revision rate is higher with aseptic loosening being the most common reason for revision. Uncemented implants appear to be associated with a lower failure rate, however, there were no modern stem designs fixed using current generation cementing techniques used in the reported studies, and as such, caution is advised when drawing any conclusions.

Updates in the pathophysiological mechanisms of Parkinson's disease: Emerging role of bone marrow mesenchymal stem cells

AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson's disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1(89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF(3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA(874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH(1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin(1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin(293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

Retrospective analysis of perianal Paget's disease with underlying anorectal carcinoma

AIM:To analyze clinical and pathological characteristics of an aggressive subtype of perianal Paget's disease(PPD) and explore its rational treatment modalities.METHODS:PPD patients were retrospectively collected in the institutional colorectal database of the Fudan University Shanghai Cancer Center.Detailed patient histories of past medical condition,diagnosis,treatment,and pathological findings were reviewed.Surgical specimen from diagnosis and surgery were reviewed by two independent pathologists for confirmation of diagnoses.Follow up was accomplished by clinical interview by cellphone.RESULTS:In total,eight cases of PPD were analyzed.All patients had underlying anorectal adenocarcinoma,including seven with synchronous lesions and one with metachronous lesions.Moreover,all anorectal lesions had a mucin-producing component.The median age at diagnosis was 65(range 29-81 years),and the male/female ratio was 7:1.The Median follow-up time of all patients was 61.5 mo(range 10-204 mo).One patient treated with abdominoperineal resection(APR) died from lung metastases 10 mo after the APR operation.The other patients are still free of disease at the time of this analysis.CONCLUSION:PPD is a rare malignancy and is easily misdiagnosed.Underlying anorectal cancer was not unusual and was a significant prognostic factor.Rational treatment of both anorectal cancer and PPD lesion is essential for long-term survival.

Bone alterations in inflammatory bowel diseases

Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental factors.Up to 50%of IBD patients experience at least one extraintestinal manifestation;among them is the involvement of bone density which is referred to as metabolic bone disease(MBD),including osteopenia and osteoporosis.Bone alterations in IBDs population appear to have a multifactorial etiology:Decreased physical activity,inflammation-related bone resorption,multiple intestinal resections,dietary malabsorption of minerals and vitamin D deficiency,genetic factors,gut-bone immune signaling interaction,steroid treatment,microbiota and pathogenic micro-organisms interaction,and dietary malabsorption of minerals,that,all together or individually,may contribute to the alteration of bone mineral density.This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility.We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.

Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease

In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer＇s disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer＇s disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

Treatment of Kümmell’s disease with sequential infusion of bone cement:A retrospective study

BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell’s disease.METHODS Patients with Kümmell’s disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed.Patients meeting the inclusion and exclusion criteria were divided into two groups:Traditional single infusion and sequential infusion(SI).The visual analog scale(VAS)and Oswestry disability index(ODI)were evaluated and compared,and duration of operation,bone cement content and complications were recorded.RESULTS Forty-five patients were included in this study;there were 24 in the traditional single infusion group and 21 in the SI group.The VAS and ODI were significantly different for both groups when compared pre-and postoperatively,whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically.When the VAS and ODI of the two groups were compared,there were no significant differences at any time point.The leakage rate of bone cement was significantly lower in the SI group(14.3%,3 of 21)than that in the traditional single infusion group(41.7%,10 of 24).CONCLUSION SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell’s disease,and this technique could decrease the incidence of bone cement leakage.

Extramammary Paget’s disease: Updates in the workup and management

Objective:Extramammary Paget’s disease(EMPD)is a rare cutaneous malignant disease.Due to its rarity,there is a paucity of data regarding best treatment strategy.EMPD primarily affects apocrine gland-bearing skin areas such as the vulva,scrotum,and penis.Our objective was to provide a present-day rationale for diagnosis,pathogenesis,and treatment of EMPD with a focus on recent progress in workup and management of the disease.Methods:Literature on EMPD until February 2022 was assessed through PubMed,MEDLINE databases,and Google scholar.A narrative review of the most relevant articles was provided.Results:EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ.The foundation of EMPD treatment centers around prompt and accurate diagnosis,wide local or Mohs micrographic surgical excision with proper management towards the margin status,and careful consideration for lymphadenectomy in patients with regionally positive disease.Conventional chemotherapies are alternative treatments modality for patients with distant metastases;however,they sometimes have suboptimal efficacy.At present,there is no agreement regarding adjuvant or systemic therapies,although recent studies have shown several insights into the molecular pathogenesis,tumor biology,and genomics of the development and advancement of EMPD,which may lead to novel and targeted treatment approaches for metastatic EMPD in the future.Conclusion:Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling.These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression.Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors,and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Updated bone mineral density status in Saudi patients with inflammatory bowel disease

BACKGROUND Little is known about inflammatory bowel disease(IBD)burden and its impact on bone mineral density(BMD)among adult patients in Saudi Arabia.To the best of our knowledge,our study is the only study to give an update about this health problem in adult Saudi patients with IBD.IBD is a great risk factor for reduced BMD due to its associated chronic inflammation,malabsorption,weight loss and medication side effects.Consequently,screening for reduced BMD among patients with IBD is of utmost importance to curb and control anticipated morbidity and mortality among those patients.AIM To assess the relationship between IBD and BMD in a sample of adult Saudi patients with IBD.METHODS Ninety adult patients with IBD-62 Crohn’s disease(CD)and 28 ulcerative colitis(UC)-were recruited from King Fahad Specialist Hospital gastroenterology clinics in Buraidah,Al-Qassim.All enrolled patients were interviewed for their demographic information and for IBD-and BMD-related clinical data.All patients had the necessary laboratory markers and dual-energy x-ray absorptiometry scans to evaluate their BMD status.Patients were divided into two groups(CD and UC)to explore their clinical characteristics and possible risk factors for reduced BMD.RESULTS The CD group was significantly more prone to osteopenia and osteoporosis compared to the UC group;44%of the CD patients had normal BMD,19%had osteopenia,and 37%had osteoporosis,while 78%of the UC patients had normal BMD,7%had osteopenia,and 25%had osteoporosis(P value<0.05).In the CD group,the lowest t-score showed a statistically significant correlation with body mass index(BMI)(r=0.45,P<0.001),lumbar z-score(r=0.77,P<0.05)and femur z-score(r=0.85,P<0.05).In the UC group,the lowest t-score showed only statistically significant correlation with the lumbar z-score(r=0.82,P<0.05)and femur z-score(r=0.80,P<0.05).The ROC-curve showed that low BMI could predict the lowest t-score in the CD group with the best cut-off value at≤23.43(m/kg2);area under the curve was 0.73(95%CI:0.59–0.84),with a sensitivity of 77%,and a specificity of 63%.CONCLUSION Saudi patients with IBD still have an increased risk of reduced BMD,more in CD patients.Low BMI is a significant risk factor for reduced BMD in CD patients.

Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson's disease

A rat model of Parkinson＇s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells （BMSCs） were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein （GFAP）, nestin and neuron-specific enolase （NSE）. Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson＇s disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.

Bone cement implantation syndrome during hip replacement in a patient with pemphigus and Parkinson’s disease: A case report

BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone cement implantation.CASE SUMMARY An 80-year-old patient with pemphigus and Parkinson’s disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation.The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline(2μg/mL)at a rate of 30 mL/h.Subsequently,the symptoms of BCIS were markedly alleviated,and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later.The patient was then transferred to the Department of Orthopedics,and anticoagulation therapy began at 12 h postoperatively.No other complications were observed.CONCLUSION This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson’s disease.

Photodynamic Therapy for Extramammary Paget's Disease:5 Cases Report

Objective： To study the therapeutic effect of photodynamic therapy for extramammary Paget＇s disease. Methods： DIOMED 630 nm diode laser was used as light source and photofrin as photosensitizer. The patient＇s lesion was irradiated for 24-72 h after administrating of photofrin. The power density was 100-150 mW/cm^2 and energy density was 150-300J/cm^2. Dosage of photofrin was 2 mg/kg. Results： Lesion darkened 24 h after irradiation and formed a scar 96-120 h after irradiation. One patient＇s lesion disappeared, three patients＇ lesion diminished apparently and one patient＇s lesion was not controlled 3 months later. Conclusion： Photodynamic therapy is an effective modality for extramammary Paget＇s disease.

An autopsy case of metastatic extramammary Paget’s disease treated with multimodality treatment including anti-HER2 therapy: What is the clinical and pathological significance of trastuzumab to the patient?

Advanced Extramammary Paget’s disease (AEMPD) shows a poor prognosis despite multimodality therapy. In recent years, it is suggested that anti-HER2 therapy may be promising for HER2-positive AEMPD. We herein present an autopsy case of a patient with AEMPD treated with multimodality treatment including anti-HER2 therapy. A 78-year-old man who diagnosed with AEMPD died after surgery and systemic chemotherapy including anti-HER2 therapy (trastuzumab). The metastatic skin lesions were immnohistologically HER2-positive. While the patients were administrated trastuzumab plus taxan (docetaxel, and paclitaxel) regimen, the metastatic skin lesion decreased, however, brain metastases were found in his brain and trastuzumab is discontinued. The skin metastasis rapidly spread over his body, leading to weakness, and he eventually died. At autopsy, the lesions of EMPD were extended distant organs including brain, although each metastasis was small and asymptomatic. The wide lesion of skin metastasis was exacerbated after discontinuation of trastuzumab, and transudate was observed due to the extensive necrosis and erosion. Our autopsy findings showed one progressive pattern of AEMPD, and indicated what is the clinical and pathological significance of anti HER2 therapy for HER2-positive AEMPD.

Repeated application of autologous bone marrow-derived stem cell therapy in patients with severe Buerger’s disease

Stem cell therapy (SCT) is a promising and prospective approach in the treatment of patients with severe peripheral arterial disorders, primarily with Buerger’s disease. However, very little is known about the duration of the effect of SCT, and to our best knowledge no data are available on the efficacy and safety of repeated SCT in patients with Buerger’s disease. Here we report on two patients with severe Buerger’s disease, who received repeated autologous bone marrow-derived stem cell therapy. Our results show that a second SCT, applied to a previously treated leg 30 or 36 months after the first treatment was efficient in both cases. After twelve months, the clinical state of the repeatedly treated lower limb improved spectacularly and non-healing ulcers healed more rapidly than after the first SCT. No severe adverse events were detected. Thus repeated SCT offers a safe and efficient treatment option for relapsing patients at the advanced stage of Buerger’s disease.

Extramammary Paget’s Disease Covered the Left Nipple and Areola

We present a case of a 71-year-old woman suffering from mammary Paget,s disease and having a 10-years history of an irregular, widespread erosion accompanied by itching and burning on the skin of her left chest, extending to the breast. The erosion had steadily enlarged and had become increasingly tender. The nipple and areola of the left breast disappeared and could not be recognized. No abnormality of the right nipple, areola, and covering skin and no supernumerary nipple were seen. Mammography and ultrasonography could not be performed because of severe pain and erosive wetness. Histopathology of a surgical biopsy specimen showed epidermal infiltration by large, round, clear atypical cells scattered individually or in small clusters and distributed horizontally throughout the epidermis. The cytoplasm of these large cells was pale and vacuolated and was equivalent to that in nipple cells in Paget,s disease, and a diagnosis of mammary Paget,s disease was made. We performed total mastectomy of the left breast with wide excision of the Paget lesion of the left chest and axillary lymph node sampling. Histological examination of the specimen showed typical distribution of Paget,s cells;however no ductal carcinoma in situ was found in the mammary ducts and invasive growth was not recognized beyond the basal membrane of the lesion. From this evidences, we established a diagnosis of large, irregulaly shaped unusual mammary Paget,s disease, not of breast cancer origin, covering the left breast, areola, and nipple.

Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson's disease

In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson＇s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2＇-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson＇s disease. Immunohistochemical staining showed that, 5-bromo-2＇-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson＇s disease.

Paget's Disease is Associated with Eleven Cancerous Regions:a Case Report and Therapeutic Strategy

Paget＇s disease of the breast is an uncommon disorder that accounts＇for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget＇s disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget＇s disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget＇s disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.