Breast cancer is one of the most common malignancies happened in female patients.The incidence of breast cancer in Chinese females has increased in recently years.Human epidermal growth factor receptor-2 (HER-2) exhibits gene amplification or high expression of receptor protein in about one third of breast cancer patients.HER-2 positive breast cancer patients has poor prognosis,high risk of recurrence and short survival.Trastuzumab is a specific inhibitor of human epidermal growth factor receptor-2 [1],which has been widely used in the treatment of HER-2-positive breast cancer patients,and trastuzumab molecular targeting therapy compared with the traditional chemotherapy,with the advantages of high specificity and low toxicity.It changes the natural disease progression of patients with HER-2-positive breast cancer and prolongs the patient's survival time.This article will review the researches on the four aspects,which including the development and the application of trastuzumab in the treatment of HER-2 positive breast cancer.

Iatrogenic traumatic biliary stricture is one of the difficult points in the biliary surgery,and operation is the only definitive treatment. The operative opportunity,surgical procedure and techniques are important for the prognosis.From January 1998 to December 2011,173 patients with iatrogenic traumatic stricture were admitted to the Eastern Hepatobiliary Surgery Hospital. According to the Bismuth classification of traumatic biliary stricture,10 patients were in type Ⅰ,22 in type Ⅱ,87 in type Ⅲ,38 in type Ⅳ and 16 in type Ⅴ.Excision of the traumatic stricture with end-to-end anastomosis was performed on 19 patients.Of the 173 patients,154 were treated by Roux-en-Y duodenojejunostomy, and 8 of them received additional hemihepatectomy or partial hepatectomy.A total of 155patients were followed up,with a median time of 74 months,the total excellent and good rate was 94.8％ ( 147/155 ).Surgery is the most effective therapy for iatrogenic traumatic biliary stricture. Optimal timing, reasonable surgical methods, strictly following the principle of biliary surgery and perfect operative skills are key points for a better prognosis.

Objective To observe the response of tumor patient’s peripheral blood T-lymphocyte subset following CT guided per-cutaneous argon-helium cryoablation.Methods 122 patients with advanced of hepatocarcinoma or renal cell carcinoma undergone CT guided percutaneous argon-helium cryoablation.The percentage of peripheral blood CD3 + ,CD4 + ,CD8 + T-lymphocyte subset and the proportion of CD4 +/CD8 + T-lymphocyte were monitored at 2 h before and 20 h after the cryoablation respectively.Results The percentage of peripheral blood CD3+ ,CD4+ and CD3+ ,CD8+ T-lymphocyte were significantly increased after cryoablation,(measured by matched t-test,P<0.05).The ratio of CD4 +/CD8+ T-lymphocyte cells had an increase of 0.130(P =0.069).Conclusion The percentage of blood T-lymphocyte subset in patients with advanced hepatocellular carcinoma or renal cell carcinoma is increased significantly,when they are treated by using CT guided percutaneous cryoablation.The patient's tumor specific immunity is enhanced by CT guided percutaneous cryoablation.

ObjectiveTo investigate the diagnosis and treatment of adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). MethodsThe clinical data of 14 cases of AIMAH from August 1972 to July 2010 were retrospectively analyzed.The cases included 5 males and 9 females with a mean age of 45 (range 26 to 58 ) years.Ten patients demonstrated typical Cushing's syndrome (CS) and 4 patients presented with weight gain,hypertension or diabetes mellitus without any signs of CS.The circadian rhythm of serum cortisol was abnormal.Low and high dose dexamethasone suppression tests failed to suppress cortisol secretion.CT scan showed bilateral enlargement of the adrenal glands with multiple macronodules.All patients underwent open surgery,including 5 cases of unilateral adrenalectomy,6 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 3 cases of bilateral adrenalectomy.ResultsIt was established by pathological examination that all patients had bilateral adrenal macronodular or adenomatoid hyperplasia.During the mean follow-up of 69 months (range 12 to 120 months),the clinical symptoms of CS disappeared after surgery in all cases.The 5 patients who received unilateral adrenalectomy had urinary free cortisol and serum cortisol within normal ranges and no further enlargement of the contralateral gland was noticed.Among the 3 patients who received bilateral adrenalectomy,1 case died of adrenal crisis on day seven post-operation.The remaining 2 cases presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy.Nelson's syndrome was not observed in the other patients.ConclusionsAIMAH has unique endocrinological and pathological features,presenting as an independent etiology of CS.Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH and long-term remission can be achieved.Bilateral adrenalectomy or unilateral adrenalectomy combined with contralateral subtotal adrenalectomy may be performed if the symptoms have not improved or recurred after unilateral adrenalectomy.

be diagnosed by imaging examination before operation.The ALT patients with large or symptomatic adrenal lipomatous lesions or preoperatively diagnosed teratoma should be given surgical treatment.

Objective To improve the diagnosis and treatment ot adrenocorticotropin-independent macornodular adrenal hyperplasia (AIMAH).Methods The clinical data of 17 cases with AIMAH from 2000 to 2011 were analyzed retrospectively,including 3 subclinical AIMAH,10 clinical AIMAH and 4 highrisk AIMAH patient,with common radiological characteristic of bilaterally enlarged adrenal glands with multiple nodules like ginger.The 3 cases of subclinical AIMAH patients presented with decreased serum ACTH,normal or slightly elevated plasma cortisol and urinary free cortisol level,no suppression following 1 mg overnight dexamethasone suppression test and absence of clinical signs of Cushing syndrome (CS).While clinical AIMAH and high-risk AIMAH presented with clinical signs of CS,elevated plasma cortisol and urinary free cortisol level,suppressed serum ACTH,loss of normal circadian rhythm in cortisol secretion and no suppression following the low-dose and high-dose overnight dexamethasone suppression test.Among the 4 cases of high-risk AIMAH,2 cases presented with osteoporosis,2 cases with hepatic dysfunction,3 cases with cardiopulmonary dysfunction,and 4 cases with severe hypertension.Three cases of subclinical AIMAH were treated with symptomatic treatment,10 cases of clinical AIMAH patients with surgical operation,4 cases of high-risk AIMAH patients with ketoconazole and surgical operation.Results Three subclinical AIMAH patients received symptomatic treatment and discharged from hospital with normal blood pressure and blood glucose.During the period of follow-up from 3 months to 3 years,endocrine results were normal.Seven clinical AIM AH patients underwent unilateral adrenal tumor resection plus ipsilateral partial adrenalectomy or total adrenalectomy.CS disappeared completely after 6 to 9 months.Two clinical AIMAH patients underwent simultaneous bilateral adrenalectomy.One case died of adrenal crisis after operation,and the other case presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy,no Nelson's syndrome happened during the follow-up for 5 years.One clinical AIMAH patient undertook unilateral adrenalectomy twice by interval,followed by routine corticosteroid replacement therapy.Followed up for 10 years,no Nelson's syndrome happened.Four high-risk AIMAH patients received ketoconazole and then underwent right total adrenalectomy.Cortisol levels returned to normal after 1 to 2 months and during the follow-up for 1 to 3 years,the laboratory examinations maintained normal.Conclusions Different treatment methods should be adapted to different subtypes of AIMAH.For subclinical AIMAH,the principal treatment is symptomatic,and close follow-up with regular adrenal imaging and endocrine examination is required.Surgical operation should be performed when clinical symptoms of AIMAH appear.Medical management is essential for high-risk AIMAH to inhibit the production of cortisol at first.Once these patients could stand the stimulation caused by operation,the adrenal glands should be resected as soon as possible.The unilateral adrenalectomy is an effective treatment for clinical AIMAH.

Objective To study the prognostic factors of survival in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib.Methods From May 2008 to Dec 2012,the clinical data of 82 cases with mRCC adminstered by sunitinib were reviewed retrospectively.The study included 60 male patients and 22 female patients,whose age ranged from 29 to 82 years [mean (56.1±11.3) years].Among them,52 cases presented hematuria,flank pain and palpable mass.The size of renal tumor ranged from 2.0 to 18.0 cm [mean (8.0±3.0) cm].The location of tumor included 41 in left kidney,37 in right kidney and 4 in bilateral kidney.The pathological tissue obtained from the operation in 69 cases and from biopsy in 13 cases.The pathological results demonstrated renal cell carcinoma in 75 cases,papillary cell carcinoma in 2 cases,chromophobe cell carcinoma in 2 cases,sarcomatoid carcinoma in 2 cases,collecting duct carcinoma in one case.The site of metastasis included lung in 50 cases,liver in 11 cases,bone in 14 cases,pancrease in 3 cases,retroperitoneal lymph node in 31 cases.In 52 cases,the ECOG scores ranged from 1 to 2.The others scores were more than 3.The average level of hemoglobin,AKP,LDH and leukocyte were (132±24)g/L,(90±65) U/L,(168±114) U/L and (6.4±2.0)×109/L,respectively.Before treatment,the abnormal cases in those parameters were 59,9,6 and 2,respectively.According to the MSKCC risk model,14 cases were classified into the high risk group and 68 cases into medium risk group.74 cases were accepted the sunitinb therapy within one year after diagnosis and 8 cases were accepted same therapy until one year after diagnosis.The overall survival (OS) rates were calculated by Kaplan-Meier method and Cox regression model was used to analyze the relationship between the influencing factors and the prognosis.Results The average OS was (21.6± 14.1) months (ranged 2.8 to 64.1 months).The survival rate at 1 st,2nd and 3rd year were 71％,64％ and 58％,respectively.Single factor analysis showed that significant prognostic factors were as follows:ECOG performance status ≥ 2 (P =0.005),clinical symptom during first clinic visiting (P =0.031),without nephrectomy (P =0.012),the number of metastatic sites ≥ 2 (P =0.015),hemoglobin before treatment (P=0.005),serum AKP level before treatment (＞126 U/L) (P=0.007),MSKCC score≥ 3 (P =0.000),the presence of liver metastases (P =0.000) and bone metastases (P =0.000) and relative dose intensity in the first month (1M-RDI) of sunitinib ≥ 50％ (P=0.000).Cox regression model showed that the beneficial predictive factors were ECOG performance status＜2 (P=0.136),no symptom during the first clinic visiting (P=0.801),serum AKP ＜126 U/L (P=0.618) before treatment,the absence of bone (P =0.068) and pancreas metastases (P =0.265).Sunitinib 1M-RDI ≥ 50％ was the independent predictive factor (P=0.000).Conclusions In targeted therapy era,there is some change in the prognostic factors for mRCC and target drug play an important role in the prognosis of mRCC.Sunitinib 1M-RDI ≥50％ is the independent predictive factor for the prognosis of renal carcinoma.

ObjectiveTo investigate the consistency between the results of passive particle agglutination test ( PPA ) and ELISA on Mycoplasma pneumonia ( M.pneumonia ) infection.Study the diagnostic value of both assays.Methods From November 2010 to May 2011,the serum samples of ]191 patients with respiratorysymptoms were collected fromAffiliatedHospitalof JiningMedical University.All samples were tested for antibody levels against M.pneumonia using PPA,and for IgM,IgG,IgA subclass using ELISA.The correlation between the results of two methods was evaluated by Kappa test and Spearman rank correlation analysis.The variances of the antibody subclasses among samples with different PPA titers and different age groups were analyzed by Kruskal-Wallis test.The infection status of patients was analyzed based on ELISA results and the clinical relevance of both assays was evaluated in comparison with clinical diagnosis for samples with high PPA titer.ResultsThe level of agreement between the results of PPA and ELISA was 84.3％,with Kappa value of 0.642 ( P ＜0.01 ).The prevalence of IgM and IgA antibody against M.pneumonia was significantly different among samples with various PPA titers ( P ＜0.05 ).The prevalence of IgM subclass was higher in chill and teeuager groups,while that of IgA and IgG were higher in elderly group.Antibody isotyping results suggested that 58.1％ of PPA positive samples (75 cases),especially 96.4％ of samples with high PPA titer ( 27 cases),were of current infection,which was in consistent with clinical diagnosis.ConclusionPPA showed good consistency with ELISA on diagnosis of Mycoplasma pneumonia infection.Antibody subclass determination hy ELISA indicates disease progression,thus to differentiate current infection from past.

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.

Objective To investigate the diagnosis and treatment of extra-adrenal pheochromocytoma(EAP). Methods The clinicsl data of 37 cases of EAP from April 2003 to April 2010 were retrospectively analyzed.Hypertension was observed in 31 cases.The typical triad of headache,palpitation and sweating was observed in 12 cases.The positive rate of plasma-free MNs and 24-hour urinary CA in diagnosing EAP was 96.8%(30/31) and 86.5% (32/37) respectively.The main localization diagnosis included ultrasonography,CT,MRI and 131I-MIBG,with positive rates of 91.7% (33/36),97.0%(32/33),90%(9/10) and 82.6%(19/23) respectively.Two patients underwent radiotherapy, and the remaining 35 cases underwent surgical treatment. Results Among the total of 37 cases,32 cases were single tumor,and five were multiple tumors.The anatomic locations of the single tumors were as follows: 14 wre adjacent to the abdominal aorta,seven in the bladder,four adjacent to the inferior vena cava,four adjacent to the renal hilum,two adjacent to the lilac blood vessel and one in the upper pole of the right kidney.Thirty cases underwent complete tumor resection,three cases underwent tumor resection plus right nephrectomy and two cases underwent partial cystectomy.Twenty-four cases were diagnosed benign and 11 cases were diagnosed malignant by pathological examination.Among 31 cases with preoperative hypertension,postoperative blood pressure returned to normal in 23 patients,blood pressure descended mildly in six cases and blood pressure was still hypertensive in two cases.Thirty-four patients were followed up for five months to seven years,during which five cases had tumor recurrence or metastases and five cases died postoperatively. Conclusions EAP is a rare neuroendocrine tumor and its accurate diagnosis is rather difficult.Plasma-free MNs and 24-hour urinary CA are important qualitative examinations.Ultrasonography,CT,MRI and 131I-MIBG scintigraphy are important methods for the localization of the tumor.Transperitoneal resection of the tumor is the preferred choice of management and adequate perioperative preparation is the key to a successful operation,including bringing down blood pressure,expanding blood volume and correcting arrhythmia.Patients with malignant EAP may be treated with 131I-MIBG after surgical therapy.