SUBMITTED 25 JAN 22 1 REVISION REQ. 13 MAR 22; REVISIONS RECD. 15 MAR 22 2 ACCEPTED 27 MAR 22 3 ONLINE-FIRST: APRIL 2022 4 DOI: https://doi.org/10.18295/squmj.4.2022.031 5 6 Evolution of Minimally Invasive Adrenal Surgery at a Tertiary Care Centre 7 in Oman 8 Najeeb AbuDraz,1 Mohamed S. Al-Masruri,1 Ghalib Al Badaai,1 Yamam Al-9 Shamari,1 Omayma Elshafie,2 *Khurram M. Siddiqui1 10 11 1Urology Division, Department of Surgery, Sultan Qaboos University, Oman; 2Endocrinology 12 Division, Department of Medicine, Sultan Qaboos University, Oman. 13 *Corresponding Author’s e-mail: Kmsiddiqui4@gmail.com 14 15 Abstract 16 Objective: We reviewed the case records of adrenalectomy cases at our institution between 17 January 2010 and December 2020 and report the outcomes of both open and laparoscopic 18 adrenalectomy (LA). Methods: This retrospective study included patients who underwent 19 adrenal surgery from January 2010 to December 2020. We recorded demographic details, 20 indications, surgical approach, intra operative data and complications. The final pathology and 21 outcome at the last follow up was also documented. Data was analyzed through the SPSS 22 program. Results: Fifty two patients underwent 61 adrenalectomy procedures. Six patients had 23 bilateral procedure and 3 patients underwent redo surgery accounting for 55 subjects. Open 24 adrenalectomy (OA) was performed on 11 patients and 44 patients underwent LA. Majority of 25 the patients (27) were obese having BMI > 30. Functional adenoma was excised in 36 patients 26 with final diagnosis of Conn’s syndrome in 15, Pheochromocytoma in 13 and Cushing syndrome 27 in 9 patients. Five patients had surgery for oncological indications. Nonfunctional adenoma was 28 excised in 13 patients, with a mean size of 8.9 cm (range 4-15 cm). The mean duration of surgery 29 was less in laparoscopic procedure (199 min) compared to open (246 min). The mean estimated 30 mailto:Kmsiddiqui4@gmail.com blood loss in LA was significantly less (108ml vs 450 ml, p-value < 0.05). Out of 55 subjects 31 only 1 patients developed Clavien-dindo grade 2 complication. Conclusion: At our institution 32 both laparoscopic and open adrenalectomy were safely performed. There is a trend to perform 33 LA and with experience the duration of surgery and EBL are demonstrating positive trend. 34 Keywords: Adrenal Gland Surgery; Laparoscopic Adrenalectomy; Open Adrenalectomy; 35 Pheochromocytoma; Adrenal Metastasis; Nonfunctional Adrenal Tumors; Oman. 36 37 Advances in Knowledge 38  This study looks at the transition of adrenal surgery from open approach to minimally 39 invasive approach at our center. 40  It provides objective evidence that adrenal surgery is feasible in Oman. 41  This study demonstrates that laparoscopic adrenalectomy is being performed with good 42 results comparable to any other good center in the world. 43 Application to Patient Care 44  Adrenal gland is located in a difficult to access location and required large surgical incision. 45 Laparoscopic surgery for adrenal gland has the unique advantage of providing excellent 46 exposure without large incision. The advancements in surgical techniques for 47 adrenalectomy and the results of laparoscopic adrenalectomy at our center provide an 48 opportunity for our patients to benefit. 49  This study shows that less blood loss, operative time and better cosmetic results of 50 laparoscopic adrenalectomy make it the standard of care for most patient requiring adrenal 51 surgery 52  The complication rate is well within internationally acceptable range 53 54 Introduction 55 Laparoscopic adrenalectomy (LA) is now recognized as the gold standard approach for adrenal 56 pathology. The post-operative analgesics requirements, hospital stay, surgical morbidity and better 57 cosmetic results are the main driving forces.1, 2, 3 LA was first described by Ganger et al in 1992 58 for Cushing disease, since then the list of indications have now expanded to include almost all 59 benign and malignant adrenal neoplasms.4 The growing experience and systematic training 60 programs have resulted in marked reduction in the duration of surgery and morbidity.5 In this study 61 we reviewed our 10-years’ experience of open and transperitoneal laparoscopic adrenalectomy 62 procedures at our institution. To our knowledge this is the first large case series from Oman 63 comparing the open and laparoscopic approach for adrenalectomy. 64 65 Methods 66 Ethics review committee approval was obtained from our institution to conduct a retrospective 67 chart review of all the adult patients undergoing adrenal surgery our institution. Ten-year period 68 from January 2010 to December 2020 was selected and using electronic medical record (EMR) of 69 the hospital information system (Trakcare® United health care systems) we identified 55 eligible 70 subjects. 71 72 Collected data included patient demographic features, comorbidities, Body mass index (BMI), 73 preoperative diagnosis, intraoperative details including surgical approach (Open/Laparoscopic), 74 duration of surgery, estimated blood loss, pathological diagnosis. The post-operative 75 complications were also recorded and graded according to Clavien-Dindo classification system. 76 Data was analyzed using SPSS program version 21.0. The analysis was done using variable graph, 77 pie-chart and frequency tables. Frequency tables provides information about mean, median and 78 standard deviation. A p-value of <0.05 was considered as statistically significant. 79 80 Results 81 Fifty two patients underwent 61 adrenalectomy procedures. Six patients had bilateral procedure 82 and 3 patients underwent redo surgery accounting for 55 subjects. Open adrenalectomy (OA) was 83 performed on 11 patients and 44 patients underwent LA. There were 13 male and 39 female 84 patients. The mean age was 44 years (range 15-70 years). 85 86 Majority of the patients (36) underwent adrenalectomy for functional tumors. Five patients had 87 surgery for oncological indication including two for metastasis from other organs. The frequency 88 of distribution of final diagnosis is illustrated in Fig1. 89 90 The median tumor size was slightly larger in the open surgery group (5 cm vs. 6.5 cm). The details 91 of difference in size are illustrated in Table 1. Nonfunctional adenoma was excised in 13 patients, 92 with a mean size of 8.9 cm (range 4-15 cm). 93 94 ASA 2 was the most common category in 63% patients. Majority of the patient were obese with 95 52% having BMI > 30, the frequency of American society of anesthesia (ASA) score and BMI 96 groups is shown in the Figure 2. 97 98 Laparoscopic adrenalectomy was performed in 44 patients and 11 underwent open adrenalectomy. 99 The mean duration of open surgery was 246 min (median 241 min) vs. 189 min (median 197 min) 100 in the laparoscopic group. In patient undergoing open surgery the estimated mean blood loss (EBL) 101 was 450 ml (100 to 1000 ml) vs. 108 ml (range 50 ml to 500 ml) in the laparoscopic group (p=0.05). 102 We also independently analyzed the unilateral adrenalectomy group and found similar trend. The 103 mean duration of surgery and EBL in unilateral laparoscopic vs. unilateral open adrenalectomy 104 were 198 min vs. 248 min and 108 ml vs. 245 ml respectively. 105 106 We used operating time as a surrogate maker to reflect the surgical expertise. After January 2017, 107 we transitioned to a subspecialty based approach and all adrenal procedures were referred to 108 urology service having a lead surgeon with dedicated interest in adrenal surgery. To assess the 109 impact of this intervention we created two groups, Time period 1(before December 2017) and 110 Time period 2 (after January 2017). We found that the mean duration of surgery reduced from 111 mean of 206 min to 145 min only. 112 113 There were no complications in majority of patients. One patient developed diarrhea related to 114 clostridium infection and 3 patients developed paralytic ileus (2 in open and 1 in laparoscopic 115 group). The frequency of complications according Clavien-Dindo system of classification of 116 surgical complications is shown in Table 2. 117 118 Three patient were treated for recurrence of disease. Two of them belong to a family with von 119 hippel-lindau (VHL) abnormality where the recurrence is not unexpected over a period of time. In 120 one patient there was a suspicion of cancer on the histopathology and the patient underwent 121 revision LA with free margins and is doing well after 4 years of follow up. 122 123 Discussion 124 Adrenal surgery for a functional tumor like Cushing’s disease and Pheochromocytoma is 125 exceptionally rewarding in terms of the physiological outcomes. The additional benefits of 126 minimally invasive approach in terms of cosmetics, minimal blood loss, lesser analgesic 127 requirement, hospital stay and higher patient satisfaction have certainly placed laparoscopic 128 adrenalectomy (LA) at the pedestal of gold standard.6, 7, 8 In this study we looked at the safety and 129 efficacy of intraperitoneal laparoscopic adrenalectomy at our institution and how it has evolved to 130 be now a routine surgical procedure. 131 132 Functional adrenal tumors present multiple challenges in the peri operative period. Significant 133 number of patients are also obese. In our study 52% of our patients had BMI of > 30, which is well 134 known to be associated with intraoperative difficulties.9, 10 Secondary hypertension is also one of 135 the common presentation of adrenal tumors. Studies have shown that almost two third of the 136 indications of surgery are for functional tumors exhibiting hypertension.11 In our study 67% 137 patients had secondary hypertension related to either Cushing disease, Pheochromocytoma or 138 Conn’s disease. Post operatively all patients were successfully weaned off the antihypertensive 139 medications. 140 141 The evolution of laparoscopic adrenal surgery has witnessed an expansion of indications. 142 Functional tumors like Pheochromocytoma which were initially regarded as out of bound are now 143 routinely treated by key-hole surgery.12 In our series we successfully performed LA on 13 patient 144 with Pheochromocytoma. Laparoscopic treatment of conditions like adrenocortical neoplasm has 145 also been reported with comparable oncologic outcome.13 We performed LA in 3 cases of primary 146 adrenocortical neoplasm with adequate surgical margins and acceptable oncologic control. 147 Adrenalectomy for metastatic disease is increasing performed and can be considered as standard 148 of care for some cancers with solitary adrenal metastasis.14 We performed laparoscopic 149 metastatectomy in 2 patients with adrenal metastasis. One of them relapsed within one year but 150 the other patient has no evidence of disease with more than 3 years of follow up. The limit of size 151 of the gland to undergo LA has always been debatable and some authorities have recommended 152 the upper limit as > 6cm.15 Technical difficulty and suspicion of malignancy are regarded as factors 153 responsible to cap the size limit.16 In our study we have performed LA for tumors up to 15 cms 154 with no significant increase in operating time or blood loss. In these cases we did not encounter 155 any incidental finding of cancer, in our opinion the advancements in radiology have increased our 156 confidence. Modern CT scan and MRI of the adrenal gland using specific protocols now have 157 excellent ability to predict the final pathology.17 In our cohort of LA for non-functional adenoma 158 the mean size of the gland removed was 5.8cm. 159 160 In our series the LA had also retained the advantage of shorter operative time with the mean 161 duration of LA as 189 min compared to open adrenalectomy with the mean of 246 min. The EBL 162 in LA is significantly less with the mean of 170ml comparing with 450ml in open procedure, with 163 the significant p-value < 0.001. 164 165 We also looked a two time periods for LA, before December 2017 and after January 2017. This 166 division was created to assess the impact of change in the referral system at our institution as from 167 January 2017 onwards all cases of adrenal tumor were referred to a team dedicated to do LA. We 168 found that the mean duration of surgery reduced from 206 min to 145 min. We must acknowledge 169 the limitation here as the cases were not controlled for complexity of procedure. 170 171 The overall rate of complications of adrenalectomy, both open and laparoscopic was very low at 172 our institution. Majority of patients did not have any complications. Out of 55 subjects one 173 developed grade 2 Clavien-Dindo complications. There we no grade 3 or above complications. 174 During follow up 3 patients had disease recurrence and underwent redo surgery. Two of them 175 belonged to a family of patients with VHL abnormality and were predisposed to high risk of 176 recurrence. One patient had suspicious pathology for adrenocortical cancer and had revision 177 surgery. 178 179 Conclusion 180 Both laparoscopic and open adrenalectomy have been performed safely at our institution with low 181 morbidity. The benefits of minimally invasive approach clearly favor laparoscopic approach 182 especially in term of duration of surgery and estimated blood loss. However in selected cases there 183 is still a role of open approach. 184 185 Authors’ Contribution 186 NA and KMS designed the study. NA, MSM and YS collected the data. NA, MSM, GB and 187 KMS performed the statistical analysis. NA and MSM drafted the manuscript. GB, OE and KMS 188 critically reviewed the manuscript and revised the manuscript. All authors approved the final 189 version of the manuscript. 190 191 Conflict of Interest 192 The authors declare no conflicts of interest. 193 194 Funding 195 No funding was received for this study. 196 197 References 198 1. Lee J, El-Tamer M, Schifftner T, Turrentine FE, Henderson WG, Khuri S et al. Open and 199 laparoscopic adrenalectomy: analysis of the National Surgical Quality Improvement 200 Program. J Am Coll Surg. 2008 206(5):953-9. doi: 10.1016/j.jamcollsurg.2008.01.018. 201 2. Elfenbein DM, Scarborough JE, Speicher PJ, Scheri RP. Comparison of laparoscopic 202 versus open adrenalectomy: results from American College of Surgeons-National Surgery 203 Quality Improvement Project. J Surg Res. 2013;184 (1):216-220. 204 doi:10.1016/j.jss.2013.04.014 205 3. Eichhorn-Wharry LI, Talpos GB, Rubinfeld I. Laparoscopic versus open adrenalectomy: 206 another look at outcome using the Clavien classification system. 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Quantitative imaging in medicine and surgery, 8(8), 242 853–875. https://doi.org/10.21037/qims.2018.09.13 243 244 245 Figure 1: The Distribution of Frequency of Diagnosis for Adrenalectomy 246 247 248 Figure 2: The Distribution of Body Mass Index (BMI) and American Society of 249 Anesthesiologist (ASA) of the Patients undergoing Adrenalectomy 250 https://doi.org/10.21037/qims.2018.09.13 Table 1: The distribution of tumor size in the two groups 251 Laparoscopic Adrenalectomy N=44 Open Adrenalectomy N=11 Mean size in cm 5.8 6.8 Median size in cm 5 6.5 Range 1.5-15 3.8-11 Standard deviation 3.49 2.22 252 Table 2: The frequency of surgical complications in the two groups 253 Clavien-Dindo Grade Total N=55 Laparoscopic Adrenalectomy Open Adrenalectomy 0 51 0 0 1 3 1 2 2 1 1 0 3 0 0 0 254