Clinical Research Of Retroperitoneal Laparoscopic Partial Adrenalectomy For Unilateral Aldosterone-producing Adenoma

BackgroundAldosterone-producing adenoma is a benign tumor,secreting excessive renin-independent aldosterone,and one of primary hyperaldosteronism’s common subtypes.Its main clinical manifestations are hypertension and hypokalemia.Conn described and reported APA the first time in 1955.Hypertension,which is a chronic disease and harm to the health,has get more and more attention of people nowadays.There are many causes of hypertension,we can provide the target treatment and cure or improve the hypertension if the cause of secondary hypertension can be found.Once PHA was considered less than 1% in the patients with hypertension,however,the number of patients diagnosed PHA have increased 5~15 times as the plasma aldosterone/renin activity ratio is used as the screening method widely.Ever APA was thought as the most common subtype of PHA,accounting for about 60% to 70%.But with the improvement of the diagnostic methods,researchers find that APA accounts for about 30%~50% and idiopathic hyperaldosteronism is the most common subtype,accounting for about 60% of PHA.Prevalence of APA is approximate 4.8%~5% in the hypertension population.Long-term effects of excess aldosterone lead to functional and physical damage to target organs including heart and kidney and so on,even lead to organ failure.Early diagnosis,assessment and treatment of APA can effectively diminish the harmful effects of excess aldosterone on the target organs.Most diameters of APA are about 1~2 cm.Unilateral APA accounts for about 90% and bilateral APA accounts for about 10%.Surgery is preferred to APA.Gagner described laparoscopic adrenalectomy firstly in 1992.Compared with the traditional open adrenal surgery,laparoscopic adrenal surgery is minimally invasive,has less complications,more rapid recovery,etc.With the continuous development and extensive application of laparoscopic technique,laparoscopic adrenalectomy has become the standard treatment of benign adrenal tumors.Laparoscopic adrenalectomy consists of laparoscopic total adrenalectomy(TA)and laparoscopic partial adrenalectomy(PA).Laparoscopic TA has curative effect on unilateral APA,however,laparoscopic PA has also received more and more recognition for unilateral APA.The choice between laparoscopic TA and PA for unilateral APA remains controversial.Resecting the tumor through laparoscopic surgery can completely prevent the APA from excessively secreting aldosterone,improve or even cure hypertension.The surgical treatment can effectively reduce the cerebrovascular accident,heart and kidney failure.Lateral adrenalectomy may cure 30%~60% and improve about 90% of the hypertension,correct almost all of the hypokalemia,high plasma aldosterone concentration and low plasma renin activity.However,some of APA patients are characterized by persistent hypertension postoperatively.Compared with other patients with primary hypertension,they have more risks of myocardial infarction,cerebrovascular accident and renal failure.Preoperatively predicting hypertension prognosis of patient with APA after laparoscopic adrenalectomy will be conducive to the communication between surgeons and patients,meanwhile,help they make the clinical decision and get the more objective and reasonable expectations about the prognosis.As reported,predictive factors of complete resolution of hypertension after adrenalectomy for APA included gender,body mass index(BMI),age,duration of hypertension,preoperative antihypertensive medicines,renal function,plasma aldosterone concentration,tumor diameter,etc.In 2008,Zarnegar established a predictive model to predict complete resolution of hypertension for APA after laparoscopic adrenalectomy,named as the aldosterone resolution score(ARS).ARS contains four preoperative clinical indicators: female,BMI≤25 kg/m2,duration of hypertension≤6 years,preoperative antihypertensive medicines≤2 types.The three former indicators were assigned 1 point respectively and the forth indicator was assigned 2 points.If they did not meet this standard,they were all assigned 0 point.Therefore,the sum of ARS ranges from 0 to 5 points.ARS was divided into three levels,they were 0~1,2~3,4~5 points.The higher the level,the greater the likelihood of complete resolution of hypertension postoperatively,the likelihood is 27%,46% and 75% respectively.ARS had been adopted into Chinese diagnosis and treatment of urological diseases Guide,however,there were few studies had validated ARS’ predictive accuracy in Chinese APA patients after PA.Objectives1.To compare the safety and clinical effects of retroperitoneal laparoscopic PA and TA for unilateral APA,and provide the basis for choosing retroperitoneal laparoscopic PA to treat unilateral APA in clinical practice.2.To analysis the predictors of complete resolution of hypertension for unilateral APA after retroperitoneal laparoscopic PA,and further validate the predictive accuracy of ARS,and provide the proof for adoption of ARS in Chinese population.Materials and methods1.Retroperitoneal laparoscopic partial versus total adrenalectomy for unilateral aldosterone-producing adenomaFrom June 2005 to March 2016,69 unilateral APA patients with complete data were treated by surgery,54 patients and 15 patients received retroperitoneal laparoscopic PA and TA respectively.A retrospective comparison about perioperative and postoperative outcomes was performed between the two groups.These characteristics included operation time,intraoperative blood loss,fasting time,retaining drainage tube time,postoperative hospital stay,complications,postoperative systolic pressure,diastolic pressure,antihypertensive medicines,plasma aldosterone concentration,plasma renin activity,plasma potassium,adrenal computed tomography and tumor recurrence.To comparw these two operation methods’ safety and clinical effects.Continuous data with normal distribution were recorded as mean±SD;Continuous data with skewed distribution were recorded as median(range);Continuous data with normal distribution were compared by means of the independent samples t-tests;Continuous data with skewed distribution or unequal variances were compared by means of the Mann-Whitney U test;Enumeration data were compared by means of the chi-square test.All data were analyzed by SPSS21.0 statistical software,P=0.05.2.Prognostic analysis of hypertension after retroperitoneal laparoscopic partial adrenalectomy for patients with unilateral aldosterone-producing adenomaFifty-four patients with unilateral APA after retroperitoneal laparoscopic PA for six months were divided into two groups,cured or not cured,according to the prognosis of hypertension.Explore the predictors for complete resolution of hypertension by univariate analysis and multivariate binary regression analysis.Validate the predictive accuracy of ARS by counting the area under the receiver-operating characteristic curve in this study.Continuous data with normal distribution were recorded as mean±SD;Continuous data with skewed distribution were recorded as median(range);Continuous data with normal distribution were compared by means of the independent samples t-tests;Continuous data with skewed distribution or unequal variances were compared by means of the Mann-Whitney U test;Enumeration data were compared by means of the chi-square test.All data were analyzed by SPSS21.0 and Medcalc11.4.2.0 statistical software,P=0.05.Results1.Retroperitoneal laparoscopic partial versus total adrenalectomy for unilateral aldosterone-producing adenoma(1)Baseline characteristics: Compared PA group with TA group,there were no significant differences in terms of gender,age,BMI,duration of hypertension,systolic blood pressure,diastolic blood pressure,preoperative antihypertensive medicines,plasma aldosterone concentration,plasma renin activity,ARR,plasma potassium,tumor location(left/right),tumor diameter,P>0.05.(2)Perioperative characteristics: Compared PA group with TA group,there were no significant differences in terms of operating time[(118.130±40.902)vs.(111.467 ±40.701)min,t = 0.559,P = 0.578],intraoperative blood loss[30(0~400)vs.30(10~300)ml,Z =-0.029,P = 0.977],fasting time [2(1~4)vs.2(1~6)d,Z =-1.346,P = 0.178],retaining drainage tube time[3(2~6)vs.3(1~7)d,Z =-0.346,P = 0.729],postoperative hospital stay[7(3~15)vs.7(4~12)d,Z =-1.111,P = 0.267].There were no blood transfusion and conversion.Some patients pathological results were adenoma accompanied by micronodules,there were 5 patients(9.3%)in PA group and 3 patients(20.0%)in TA group,the difference was not significant(χ~2=0.481,P=0.488).(3)Clinical efficiency: After the follow-up for six months,all patients had the normal plasma aldosterone concentration,plasma renin activity and plasma potassium.Compared PA groups to TA group,decreased systolic pressure value[(57.611±22.813)vs.(57.457±25.826)mm Hg,t=0.021,P=0.983],decreased diastolic pressure value [28.630±14.413)vs.(29.400±10.802)mm Hg,t=-0.192,P=0.848],decreased ARR value [(75.978 ±48.521)vs.(64.462± 29.788),t=0.872,P=0.386],increased plasma potassium value [(0.841±0.780)vs.(1.073±0.555),t=-1.079,P=0.285] all had no significant differences.These two groups’ cure rates,improvement rates and invalid rates of hypertension respectively were(51.9%、37.0%、11.1%)vs.(53.3%、40.0%、6.7%),there were no statistical differences(Z=-0.227,P=0.820).Follow-up time was 6 to 99 months(mean 34 months),there were no recurrences.2.Prognostic analysis of hypertension after retroperitoneal laparoscopic partial adrenalectomy for patients with unilateral aldosterone-producing adenoma(1)Groups derived from hypertension prognosis: There were 54 patients with unilateral APA involved in this study.At 6 months after retroperitoneal laparoscopic PA,cured group was composed of 28 patients(51.9%)had normal blood pressure without any antihypertensive medicines and not cured group was composed of 26 patients(48.1%)had persistent hypertension.(2)Univariate analysis of preoperative clinical characteristics: Compared cured group to not cured group,there were no significant differences in terms of gender,BMI,systolic pressure,diastolic pressure,family history of hypertension(without/with),smoking history(without/with),drinking history(without/with),plasma aldosterone concentration,plasma renin activity,ARR,plasma potassium,plasma sodium,plasma glucose,plasma urea nitrogen,plasma creatinine,urine specific gravity,urine protein(negative/positive)and plasma cortisol rhythm(normal/abnormal),24 hours urinary methoxy-norepinephrine,24-hour urinary methoxy-adrenaline,tumor location(left/right),tumor diameter(P>0.05).There were significant differences in terms of preoperative age[(39.000 ± 9.580)vs.(49.500 ± 9.335)years,t=-4.074,P=0.000],duration of hypertension[1(0 ~ 10)vs.8(3 ~ 20)years,Z=-4.603,P=0.000],antihypertensive medicines[2(1~5)vs.3(1~5)types,Z=-3.973,P=0.000],plasma uric acid[(354.179±91.575)vs.(430.577±150.381)μmol/l,Z =-2.026,P=0.043].(3)Multivariate binary logistic regression analysis: These two indicators,duration of hypertension≤2 years and antihypertensive medicines≤2 types preoperatively,were the predictors of complete resolution of hypertension for patients with unilateral APA after retroperitoneal laparoscopic PA.Their OR,95% CI,P value were(13.535,3.000~61.076,0.001)and(9.729,1.998~47.367,0.005)respectively.(4)Validation analysis of ARS: In this study,the complete resolution rates of hypertension are 18.8%,42.9%,79.2% in the 0~1,2~3,4~5 three levels of ARS respectively.0~1 level of ARS had a negative predictive value of 81.2%,4~5 level of ARS had a positive predictive value of 79.2%.Analyzed by receiver operating characteristic curve,the area under the ROC was 0.815,95% CI was 0.701~ 0.930.Conclusions1.To treat patient with unilateral APA,retroperitoneal laparoscopic PA was technically safe and feasible,moreover,there was no significant difference of clinical effect between retroperitoneal laparoscopic PA and TA.Retroperitoneal laparoscopic PA is worthy of being prompted clinically.2.There were 51.9% of the patients with unilateral APA had the normal blood pressure without any antihypertensive medicines at the follow-up of 6 months after received retroperitoneal laparoscopic PA.3.Patient who had the duration of hypertension≤2 years and antihypertensive medicines≤2 types preoperatively was more likely to be cured hypertension.4.ARS had a high predictive accuracy in predicting patient with unilateral APA who was inclined to have complete resolution of hypertension after retroperitoneal laparoscopic PA in Chinese population.