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Objective We aimed to investigate the overexpression of succinic dehydrogenase (SDH) B and MIB-1 in patients with pheochromocytoma/paraganglioma(PHEO/PGLs) and its significance for predicting the clinical malignant behavior.Methods From August 2008 to April 2016,the clinical characteristics of 93 patients with PHEO/PGLs were analyzed retrospectively.There were 57 males and 36 females,with an average of 34 years,ranging 8-73 years old.There were 68 cases of adrenal pheochromocytoma and 25 cases of paraganglioma.There were 79 cases with hypertension and 14 cases of adrenal accidental tumors.Sixty-six cases with typical hyper-catecholamine secretion symptoms and 27 cases with non-functional PHEO/PGL.Benign PHEO/PGLs were 77 cases and malignant 16 cases.The tumor was located on the left side in 39 cases,on the right side in 32 cases and multiple lesions in 22 cases.The diameter of the PHEO/PGL tumor was (6.8 ± 2.7) cm.The 24 h urine catecholamine was measured before operation,which showed epinephrine was (42.6 ± 5.1) μg/24 h,norepinephrine was (167.5 ± 13.5) μg/24h and dopamine was (246.4 ± 71.2)μg/24h.Six cases wihtout hereditary diseases of urinary system were selected as normal control group.SDHB,SDHAF2,SDHC,SDHD,VHL and RET gene mutations were detected in all patients.Immunohistochemical panel has been performed to detect the expression of SDHB,MIB-1,EPAS1,VEGF-1 receptor (VEGF-1 R),and chromain A (CgA) in 93 specimens of PHEO/PGL tissue.The positive granular cytoplasm staining ＞ 50％ was strongly positive (+ + +),11％ to 50％ was moderately positive (+ +),1％ to 10％ was weak positive (+) and the negative was compared with the known positive internal reference,that is,there was less than 1％ or no stain completely.Results SDHB,SDHAF2,SDHC,SDHD,VHL and RET gene mutations in 27 cases (29.5％).Nine patients with SDHB gene mutation (9.7％).RET proto-oncogene mutations in 8 cases (8.6％).3 cases had VHL mutation (3.2％).Immunohistochemical staining showed that MIB-1 positive expression was found in 7 of 9 patients with SDHB gene mutation.Six cases in the control group were negative for gene detection and MIB-1,EPAS1,CgA and VEGF-1R immunohistochemical results.EPAS1 showed moderately positive in patients with PHEO/PGL and strong positive in patients with malignant PHEO/PGL.In 9 cases with SDHM mutation,EPAS1 was noticed positive in seven cases,which showed the relationship with CgA,MIB-1 and VEGF-1R.Conclusions The SDHB gene mutation is usually shown as a paraganglioma focus outside the adrenal gland.And 9.8％ of the paragangliomas were associated with a mutation of the SDHB gene with an increase in malignant risk.The SDHB mutation caused over-expression of MIB-1 and the positive expression of EPAS1 and VEGF-1R in PHEO/PGL tissues,which was associated with invasion and metastasis of malignant PHEO/PGL.
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Objective To discuss and evaluate the clinical efficacy and safety of sunitinib for patients with advanced renal cell carcinoma and further to analyze the associated prognostic factors.Methods A retrospective analysis was performed in 78 cases with advanced renal cell carcinoma, receiving sunitinib therapy from April 2009 to December 2014.Patients consisted of 53 males and 25 females, with median age of 54 years old, ranged from 25-85 years old.Therapeutic regimen was described as following: 52 cases receiving sunitinib 50.0 mg/d 4 weeks on and 2 weeks off (4/2 regimen), 26 cases receiving 50.0 mg/d 2 weeks on and 1 weeks off (2/1 regimen).The dosage and regimen were adjusted according to the severity of side effects.Efficacy evaluation and drug-related toxicity were based on RECIST version 1.1 and CTCAE version 3.0.Progression-free survival (PFS) and overall survival (OS) were evaluated using the KaplanMeier method.Univariate and multivariate Cox proportional hazards model were used to assess the risk factors of PFS and OS.Results Nineteen cases switched from 4/2 to 2/1 regimen.Attenuated dosage was allowed in 49 cases to ameliorate drug-related toxicities.The most common drug-related toxicities were handfoot syndrome (HFS) in 63 cases (80.8％), diarrhea in 59 cases (75.6％), fatigue in 59 cases (75.6％) and thrombocytopenia in 6 cases (71.8％).The most common grade Ⅲ-Ⅳ toxicities were HFS in 9 cases (11.5％), thrombocytopenia in 6 cases (7.7％) and hypertension in 5 cases (6.4％).In RECIST evaluation, complete response (CR) was not recorded.8 cases (10.3％) achieved partial response (PR) , 59 cases (75.6％) kept stable disease (SD) and 11 cases (14.1％) suffered progressive disease (PD).The objective response rate (ORR) was 10.3％ and the disease control rate (DCR) was 85.9％.The median PFS was 11.0 months and median OS was 21.8 months.Multivariate Cox proportional hazards model showed two independent risk factors for PFS, including number of metastasis organs ≥ 2 and a high ECOG score.One independent risk factor for OS was number of metastasis organs ≥ 2.Conclusions Sunitinib shows encouraging efficacy and safety for patients with advanced renal cell carcinoma.Patients with multiple metastatic organs and poor performance status seems to be high risky of poor prognosis.
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Objective To investigate the safety and clinical significance in presurgical application of tyrosine kinase inhibitor (TKI) targeted therapy in high-risk renal-cell-carcinoma patients.Methods TKI targeted therapy was applied to 33 high-risk renal-cell-carcinoma patients from Jun.2010 to Dec.2013,7 cases with paraneoplastic symdromes and 1 with bilateral lesions received surgical treatments.There were 6 males and 2 females in this group with average age of 50 (42-56) years.They were high-risk patients because of renal tumor and vena caval tumor thrombus in 3 cases,renal tumor and vena caval tumor thrombus and hypercalcinemia in 1 case,renal tumors with metastasis to lung and lymph nodes in 2 cases,renal tumor with metastasis to lung and bones in 1 cases,and bilateral kidney cancer in 1 case.The clinical stages included 3 cases of T3aN1M1 and T3bN0M0 respectively,and 1 case of T3bN0M1 and T3aN0M0,respectively.The primary metastasis sites were lymph nodes and lung (3 cases respectively),and another 1 in bone.4 cases suffered from vena cava tumor thrombi with 3 staged Mayo Ⅲ and 1 Mayo Ⅳ.7 cases with paraneoplastic syndromes were contra-indicated for surgery due to poor ECOG performance score (with score 3 in 3 cases and 2 in 4 cases).4 cases received Sorafinib 400mg po bid and the other 4 Sunitinib 50 mg po qd,4 weeks on and 2 weeks off,with duration of 8-12 weeks.Medical therapy ceased 6 to 16 days (median 12 days) before operation.Results Patients with neoadjuvant therapy experienced good toleration.The 7 cases with poor ECOGs improved during medical therapy.The tumor sizes in the bilateral lesions shrunk remarkably.All 7 patients received surgery:3 radical nephrectomies,4 nephrectomies and resections of Vena Caval tumor thrombus,and 1 bilateral lesions underwent nephron sparing surgery.Operations were successful though with mild to moderate adhesion,and the blood loss ranged from 120 to 500 ml,with averaged of 280 ml.Pathologic results were clear-cell renal carcinomas.All incisions were well-healed.4 patients with metastasis continued TKI therapy.All patients were alive without recurrence during the follow-up of 4 to 42 mon.Conclusions Presurgical application of targeted therapy is safe and may increase the opportunity of surgery for some patients with poor general situation,also patients with bilateral lesions may benefit from it for its possibility of nephron sparing.
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Objective To investigate the prognostic related factors in patients with renal cell carcinoma(RCC) and bone metastases,treated by targeted therapy.Methods Forty-five patients with RCC and osseous metastases were treated by targeted therapy between June 2006 and April 2013.The mean age was 59 years (range 32-81 years) with 33 male cases and 12 female cases.Twenty-seven cases were diagnosed as RCC accompanied with bone metastases initially,and the median time between the diagnosis of RCC and that of osseous metastasis for the other 18 cases was 12.5 months.All the cases underwent target therapy with sorafenib in 38 cases and sunitinib in 7 cases.Data was retrospectively analyzed and the relationship between several clinical features and overall survival (OS) was examined univariately.The Cox proportional hazards model was then performed multivariately to identify the independent risk factors.According to the independent risk factors,RCC patients with osseous metastases were categorized into high risk group (≤ 1 favorable factors) and low risk group (＞ 1 favorable factors).The median OS in those groups was compared.Results The median OS from the diagnosis of bone metastasis was 19 months,and overall survival was 74.7％ at 1 year,and 32.7％ at 2 year.Clinical features correlated with longer survival in the multivariate analysis were the absence of osseous metastases when initially diagnosed as RCC (HR:2.401,95％CI:1.210-5.699),the resection of primary renal tumor (HR:2.635,95％CI:1.021-6.307) and the absence of extraosseous metastases (HR:2.323,95％CI:1.003-6.221).The median OS of high risk group in 23 patients was 16months.On the other hand,22 patients in the low risk group had a longer median OS with 22 months.There was a significant difference in median OS between the two groups (P＜0.05).Conclusions The three prognostic factors including the absence of osseous metastases when initially diagnosed as RCC,the resection of primary renal tumor and the absence of extraosseous metastases could be favorable factors for RCC patients with bone metastasis treated with target therapy.
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Objective To investigate the clinical features of urothelial carcinoma in a single center.Methods The clinical data of 2 115 urothelial carcinoma patients admitted to Peking Union Medical College Hospital from January 2003 to December 2012 were reviewed retrospectively.Of the 2 115 patients,1414 cases were bladder carcinoma,329 cases were ureter carcinoma and 372 cases were renal pelvic carcinoma.Statistical method was used to analyze the differences of distribution and pathological grading and staging of bladder,ureter and renal pelvic carcinoma among different ages,genders,and urban and rural patients.Results The proportion of low-grade carcinoma was 83.5％ for bladder,68.7％ for ureter and 46.5％ for renal pelvic carcinoma,and the proportion of non-muscle invasive carcinoma was 84.9％,74.8％ and 59.7％ respectively,and significant difference was found in pathological grading and staging among the three groups (P =0.000).In bladder and renal pelvic carcinoma patients,males were common,while females were more common in ureter carcinoma patients.There was significant difference in gender among the three groups (P =0.000),while there was no significant difference in pathological grading and staging between male and female patients(P＞0.05).89.7％ (1 898 cases) were concentrated in the 41-80 years old.The grading and staging of urothelial carcinoma in young,middle-aged and elderly groups showed significant difference (P＜ 0.05).The proportions of high-grade and muscle invasive urothelial carcinoma patients in rural areas were both higher than that in urban areas,the difference in pathological grading and staging between urban and rural patients was significant (P＜0.05).Of the 129 cases (6.1％) with multifocal urothelial carcinoma,there were 89 cases (70.0％) with high grade and 62 cases (48.1％) with muscle invasive carcinoma.Significant difference was found in pathological grading and staging between multifocal and single urothelial carcinoma (P=0.000).Conclusions In the uretholial carcinoma of Peking Union Medical College Hospital in the past ten years,the proportion of bladder carcinoma is the highest,while ureter and renal pelvic carcinoma have higher proportion of high grade and stage.The proportion of patients in the 41-80 years old is higher.The pathological grading and staging of urothelial carcinoma is positively correlated with age,but there is no significant correlation in gender.The patients with high grade and stage carcinoma in rural areas are more than that in urban areas.Multifocal urothelial carcinoma has higher malignancy.
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Objective To detect the genetic mutations of succinate dehydrogenase B (SDHB),SDHC,SDHD,SDHAF2 and RET,VHL in hereditary pheochromocytoma (PHEO) paraganglioma (PGL) syndrome in order to analyze the relationship between the pathogenesis and SDHx mutations and DNA methylation.Methods SDH genes,VHL and RET were analyzed for germline mutations in 97 PHEOs/PGLs patients.Correlations were analyzed between the results and the clinical characteristics including age,tumor localization,multifocality,24 h urine CA,IGF and NSE.Direct DNA sequence analysis was carried out for SDHB (1q36.1-1q35,exons1-8),SDHC (1q21,exons 1-5),SDHD (11q23,exons 1-4),SDHAF2 (11q12.2,exons 1-4),RET (10q11.2,exons10,11,13,14&15,and 16) and VHL (3p25.3,exons 1-3) genes,and promoter region methylation of SDHB was detected in PHEO/PGL peripheral blood samples.Results Germinal mutations were found in 17 patients (17.5％),with 8 cases in RET proto-oncogene (8.2％),7 cases in SDHB genes (7.2％) and 2 cases in VHL gene (2.1％).The comparison of some of the clinical features in two groups (with and without promoter region methylation of SDHB) showed significant differences (P＜0.01).Conclusions Genetic predisposition is frequent in chromaffin tissue tumors,indicating that DNA analysis is necessary.The mutation of SDHB is highly associated with abdominal PGL and the following distant metastasis (malignant PGL).
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The patient is a 75 years old man complaining of ear plug and hearing loss for about three days. Physical examination shows liquid in two tympanic cavities. Chronic congestion occurs to nasal mucosa. Bilateral inferior turbinates are a little bigger than normal. Both inferior meatus are unblocked and pharyngeal recess is smooth. This patient is fat. Bilateral eye lids are swollen. A tumour could be touched in bilateral parotids with good movement and no tenderness. Its size is as big as an egg. Several lymph nodes could be touched under the jaw. The blood test is normal and IgG, IgA, IgM, ANA, anti-ENA, C3, C4, CRP and ESR is normal but RF is high. The function of liver and kidney is normal. B-mode ultrasonography result shows bilateral parotids are diffusely swollen and several swollen lymph nodes in cervix. Pathology examination of lower mandibular lymph node and parotid shows follicular lymphaticus hyperplasia with several plasmacytes and eosinophil granulocytes. The diagnosis accords with Kimura disease.
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Aged , Humans , Male , Angiolymphoid Hyperplasia with Eosinophilia , Otitis Media with EffusionABSTRACT
Objective To explore the clinicopathologic features,diagnosis,treatment and prognosis of ACTH-independent subclinical Cushing syndrome caused by cortisol-secreting and hypo-androgen black adrenal cortical adenomas with lipomatous metaplasis.Methods The clinical and pathologic features of 1 patient presented with hypo-androgen and atypical signs and symptoms of Cushing syndrome were reported.The patient's 24 h UFC (235.62 μg) was higher than normal range,his plasma ACTH concentrations (＜1.1 pmol/L,was lower than normal range and his serum cortisol concentrations lacked diurnal rhythm.There was absence of serum cortisol suppression in overnight dexamethasone suppression tests.Serum levels of androgens (1.2 nmol/L) were lower than normal range.24 h urine catecholamine was normal,NE was 160.5 nmol/24 h (5-591 nmol/24 h),E was 23.1 nmol/24 h (0-82 nmol/24 h),DA was 1496nmol/24 h (424-2612 nmol/24 h).Aldosterone lying and standing test:ALD1 138-415 pmol/L,AT-Ⅱ1 64.54 ng/L,PRA1 0.80 μg · L-1 · h-1 Abdomen CT showed right adrenal mass (3.1 cm).131Ⅰ-MIBG scanning was normal.Adrenocortical carcinoma was considered as a possible diagnosis based on cortisol hypersecretion,hypo-androgen and the imaging characteristics.This patient accepted laparoscopic adrenal adenoma resection.Results The adrenal tumor size was 3.5 cm.Immunohistochemical (IHC) staining showed Melan-A,CgA,α-inhibin and Syn positive and Ki-67 ＜ 1％.Histopathologic results showed black adrenal cortical adenomas with myelolipomatous change.After surgery,patient's serum androgen was normal,and the signs and symptoms of Cushing syndrome and oligo-androgen disappeared.There was recurrence after 1.5 years follow-up.Conclusions Although most patients with corticotropin-independent Cushing syndrome associated with abnormal androgen proved to have adrenocortical carcinoma,the clinician should be aware of the possibility of benign,black adrenal adenoma.
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OBJECTIVE@#To investigate the distribution and descriptions of the common antigens of allergic rhinitis occurred in the population of Kunshan district so as to provide evidence for clinical diagnosis,treatment and prevention.@*METHOD@#Eight hundred and twenty allergic rhinitis patients were examined skin prick test (SPT) with 18 kinds of antigen extract of allergic rhinitis.@*RESULT@#Six hundred and ninety-four (84.6%) cases were detected at least one antigen, 581 (83.7%) cases were detected two or more antigens. The most common antigens among all the positive cases of skin prick tests were dust mite 492 (70.9%), house dust mite 473 (68.2%), crab 32 (4.5%) and egg white 26 (3.7%).@*CONCLUSION@#Mite, crab and egg white are the most common antigens of allergic rhinitis in Kunshan. SPT is important for the diagnosis, treatment and prevention.
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Adolescent , Adult , Aged , Animals , Child , Female , Humans , Male , Middle Aged , Young Adult , Allergens , Allergy and Immunology , China , Epidemiology , Mites , Allergy and Immunology , Rhinitis, Allergic, Perennial , Epidemiology , Skin TestsABSTRACT
Objective To explore clinicopathologic features,diagnosis,treatment and prognosis of von Hippel-Lindau (VHL) type 2B mixed cutaneous leukocytoclastic vasculitis. Methods A 22-Year-Old Man who presented with constitutional symptoms,severe hypertension,and purpuric lesions over the knees.Clinical features,histopathological,IHC and anti-angiogenesis therapy of this case with VHL syndrome-2B mixed cutaneous leukocytoclastic vasculitis was studied based on the available follow-up data.He underwent laparoscopic adrenalectomy and nephron sparing nephrectomy.Clinical evaluation included ophthalmologic examination as well as imaging exams and endocrinal hormone test for tumors markers ; molecular analysis consisted of PCR amplification of the complete VHL gene coding sequence (three exons) and automated nucleotide sequencing. Results 24 h urine Norepinephrine was 295.84 μg and octreotide scan was positive.The VHL-2B patient suffered from leukocytoclastic vasculitis,a retinal hole,pancroatic tumors (endocrine tumor and microcystic cystadenoma),bilateral pheochromocyoma,clear renal cell carcinoma,renal cysts,hepatic hemangioma and epididymal cyst.The patient developed 5 different tumors related to VHL within a period of 6 years.The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids,but rapidly resolved after treatment with phenoxybenzamine and removal of bilateral pheochromocytomas.Tumor cells of resected PHEO samples stained positive for CgA and S-100,but negative for Melan-A.,and with less than 1％ Ki-67. Conclusions Cutaneous leukocytoclastic vasculitis is one of paraneoplastic syndrome of pheochromocytoma.Because new lesions may develop during the patient's lifetime,regular clinical inspection is recommended in order to check up the development of any new lesions.
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Objective To discuss the clinical and pathological manifestations of paragangliomas of the urinary bladder (PUB) and improve the preoperative diagnosis and surgical treatment of PUB.Methods Clinical data of 11 patients treated for PUB from June 1985 to March 2010 were analyzed.All cases had mild-paroxysmal hypertension, palpitation, sweating, and 9 cases occasionally showed headache and micturition syncope during straining urination. Twenty-four hour urine catecholamine (CA) levels were estimated in all cases. B-ultrasound and CT and/or MRI scanning were used in the imaging of all cases. Nailfola microcirculation inspection was carried out in 5 cases. Scintigraphy 131I-MIBG in 4 patients was positive expression, 7 of 111 In-DTPA-Octreotide scintigraphy and I of PETCT were also positive expression. UICC bladder tumor classification was T1 (1 case), T2 (5 cases), T3(4 cases), T4 (1 case). Results All the patients underwent partial cystectomy, laparoscopy or TURBT. One patient received 131 I-MIBG therapy. Histopathological diagnosis was confirmed by HE staining in all of the removed tumors. The tumors consisted of discrete aggregates of zellballen cells separated by a network of vascular channels. Follow-up ranged from 3 to 291 months (mean, 45 months). There were 3 recurrences following surgery. One patient died after developing pelvic lymph nodes, liver and colon metastasis. Conclusions PUB should be suspected in patients below 40 years of age if the clinical manifestations of typical tetrad symptoms: headache and micturition syncope,sweating, palpitation and hematuria are present. Advanced classification, multifocal tumors and CgA (+) are risks of recurrence and metastasis. In those patients with unresectable multiple or recurrent tumors, chemotherapy and 131I-MIBG therapy may be helpful for controling hypertension and delaying progress.
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ObjectiveTo investigate the clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer.MethodsOne hundred and twenty-four patients who had undergone thoracic esophageal resection with recurrent laryngeal nerve lymph node dissection in our hospital from March 2007 to February 2010.All clinical data were retrospectively analysed.ResultsRecurrent laryngeal nerve lymph node metastasis was found in 34 of 124 cases,with the metastatic rate of 27.41% (34/124).The left recurrent laryngeal nerve lymph node metastasis was 16.13% and the right was 8.06% .The recurrent laryngeal nerve lymph node metastasis was found in 9 patients with the upper segment esophageal cancer,20 with middle third esophageal cancer and 5 with lower segment esophageal cancer,6 patients with T2 disease had recurrent laryngeal nerve lymph node metastasis,while 27 with,T3 disease.Also there were 4,13,17 cases with metastasis in well-differentiated,moderately differentiated,poorly differentiated respectively.Poorly differentiated esophageal carcinoma was more susceptible to recurrent laryngeal lymph node metastasis than well-differentiated and moderately differentiated esophageal carcinoma.Recurrent laryngeal nerve injury was found in 11 cases,7 cases of them recovered.ConclusionNearly 1/3 of patients with esophageal carcinoma have recurrent laryngeal nerve lymph node metastasis,especially for tumor located in the upper third esophagus,poor differentiation or deep invasion (T2 or more) of esophageal carcinoma were more susceptible to recurrent laryngeal nerve lymph node metastasis.
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Objective To investigate the clinical manifestations, pathologic features, treatment and prognosis of oncogenic osteomalacia (OO). Methods A 17-year-old male patient was admitted.The patient presented with a 4-year history of progressive lower limb weakness, muscle atrophy and joint pain. Lab tests demonstrated hypophosphatemia. Lumbar and pelvic X-ray showed wedging of the lumbar spine and decreased pelvic bone density. Ultrasonography revealed a low-echo and bloodrich mass measuring 15.1 cm× 14.5 cm× 13.2 cm located at the lower pole of left kidney. Computed tomography showed a voluminous enhanced tumor, supplied by the left renal artery, vice renal artery and a branch of the inferior mesenteric artery. A tortuous vein at the lower part of the tumor drained into the left renal vein. A radioactive octreotide scan was used to study an increased radionuclide-uptake lesion which was initially suspected on the CT scan. The patient was preoperatively diagnosed with left malignant kidney tumor and oncogenic osteomalacia. During a left radical nephrectomy performed through a transperitoneal anterior subcostal incision, a round diameter 15 cm tumor covered by twisted veins was found. The patient recovered well postoperatively. Results The histological diagnosis was renal clear cell carcinoma. Immunohistochemical staining detected Vimentin and RCC were positive and Ki-67antigen index was about 2 %. After lesion removal, the paraneoplastic syndrome resolved. At the 11-month follow-up, no recurrence of the disease was observed. Conclusions Oncogenic osteomalacia is rare and OO with renal cell carcinoma has not been reported so far. OO or rickets should be suspected in those patients who presented with metabolic bone disease associated with hypophosphatemia and inappropriate phosphaturia. If OO syndrome was suspected, in addition to past medical history and imaging, a standard meticulous examination should be initiated promptly. Surgical treatment is still necessary once confirmed. And all of them achieved a good prognosis.