JOURNAL OF ENDOUROLOGY Volume 28, Number 6, June 2014 ª Mary Ann Liebert, Inc. Pp. 686–692 DOI: 10.1089/end.2013.0706
Surgical Outcome of Laparoscopic Surgery, Including Laparoendoscopic Single-Site Surgery, for Retroperitoneal Paraganglioma Compared with Adrenal Pheochromocytoma Seiya Hattori, MD,1 Akira Miyajima, MD, PhD,1 Yousuke Hirasawa, MD,1 Eiji Kikuchi, MD, PhD,1 Isao Kurihara, MD, PhD,2 Kazutoshi Miyashita, MD, PhD,2 Hirotaka Shibata, MD, PhD,3 Ken Nakagawa, MD, PhD,1 and Mototsugu Oya, MD, PhD1
Abstract
Objective: Paraganglioma (PGL) is a rare type of tumor that arises from the extra-adrenal paraganglia. A PGL tumor hypersecretes catecholamines and causes symptoms identical to those in patients with hyper-functioning adrenal pheochromocytoma (PCC). In this study, we compared the surgical outcome of laparoscopic surgery, including laparoendoscopic single-site (LESS) surgery, in patients with PCC and patients with retroperitoneal solitary PGL. Methods: The records of 49 patients with PCC and 9 patients with unilateral retroperitoneal PGL at our institution from January 2001 to March 2013 were retrospectively reviewed. Multiple tumors, tumors suspected of being malignant preoperatively, and tumors operated on using a retroperitoneal approach were excluded from the study. Results: Each group was equivalent with respect to patient background, hemodynamic variables, and preoperative biochemical assessments, including plasma catecholamine levels and catecholamine levels in 24-hour urine samples. The mean operative time was significantly longer in the PGL group (149.4 – 56.5 minutes v 189.8 – 44.9 minutes, P = 0.019). In univariate and multivariate analyses, tumor size ‡ 50 mm and PGL were statistically significant factors that predicted prolonged operative time. Intraoperative hypotension occurred in 15 patients in the PCC group and in 8 patients in the PGL group, and the difference was statistically significant (P = 0.002). One postoperative complication in the PCC group and two postoperative complications (Clavien-Dindo grade II or higher) in the PGL group were observed, and the difference was statistically significant (P = 0.012). Twenty-two patients in this series underwent LESS surgery (PCC: n = 19; PGL: n = 3), and there was no statistically significant difference in the perioperative outcomes between the two groups. Conclusions: The present results demonstrate that the operation for solitary extraperitoneal PGL required a longer operative time and had more hypotensive episodes and higher postoperative morbidity than the PCC group. Though the perioperative outcome of LESS surgery for PGL is comparable to that of PCC, we should treat the patients with PGL accordingly.
Introduction
P
araganglioma (PGL) is a rare tumor that arises from extra-adrenal paraganglia. A PGL tumor hypersecretes catecholamines and causes symptoms identical to those in patients with hyper-functioning adrenal pheochromocytoma (PCC). The treatment of choice for both PCC and PGL is surgical resection, and most tumors are benign and can be completely excised. Since the first case of laparoscopic re-
moval of a PCC, there has been adequate discussion of the safety of performing laparoscopic surgery for PCC because of the increased morbidity and adverse hemodynamic sequel. Recently, many reports have indicated that laparoscopic surgery is superior to open surgery in patients with PCC in terms of postoperative pain, rapid convalescence, and short hospital stay if performed with careful hemodynamic monitoring.1–5 With recent advances in laparoscopic techniques, instrumentation, and anesthetics combined with
Departments of 1Urology and 2Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 3 Department of Endocrinology and Metabolism, Oita University, Oita, Japan.
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vastly improved preoperative imaging capabilities, laparoscopic surgery for adrenal PCC is widely considered to be the current gold standard approach.5–7 Operative time for laparoscopic surgery in PGL patients, however, is reported to be significantly longer than that of PCC,8 suggesting increased difficulty with laparoscopic surgery for PGL. As PGL is a rare type of tumor, only a few reports have investigated the surgical outcome of laparoscopic or laparoendoscopic single-site (LESS) surgery for retroperitoneal PGL compared with that of adrenal PCC, especially with respect to intraoperative hemodynamic changes and morbidity. The aim of this study was to compare the surgical outcome of laparoscopic surgery, including LESS surgery, in patients with PCC and patients with solitary, retroperitoneal abdominal PGL, paying attention not only to immediate postoperative outcomes but also to the intraoperative hemodynamic changes. Methods
Records of 62 consecutive patients with PCC or PGL who underwent unilateral laparoscopic adrenalectomy or retroperitoneal tumorectomy at our institution from January 2001 to March 2013 were entered into a database. Patients with a tumor suspected preoperatively of malignancy (n = 1; one PCC patient) and patients with insufficient perioperative data (n = 2; one PCC patient and one PGL patient) and/or a tumor operated on using a retroperitoneal approach (n = 1; one PCC patient) were excluded from the study. In the end, 49 patients with PCC and 9 patients with unilateral retroperitoneal PGL were included. All of the PGL were located in the perirenal hilum (n = 7) or para-aortic area (caudal to the renal vessels: n = 1; upper to the renal vessels: n = 1). Among these patients, 22 had undergone LESS surgery (PGL, n = 3: perirenal hilum, n = 2; para-aortic, caudal to the renal vessels, n = 1). a-adrenergic blockade was initiated at least 2 weeks before surgery, and b-adrenergic blockade was added in patients with coexisting tachycardia. All patients underwent CT, MRI, and/or 123iobenguane m-iodobenzylguanidine (123I mIBG) scintigraphy preoperatively. Preoperative biochemical assessments included the measurement of plasma catecholamine levels and catecholamine and metabolite levels in 24-hour urine samples. Surgical procedures were performed or supervised by two skilled laparoscopic surgeons (A. Miyajima and K. Nakagawa), who to date have performed more than 500 cases of urologic laparoscopic surgery together. All operations used a transperitoneal approach. The selection of surgical procedure (LESS or conventional laparoscopic surgery) was left to the surgeon’s preference. In LESS surgery, we operated through the umbilicus (14 cases) or beside the navel (8 cases). The multichannel port (SILS port, Covidien, Mansfield, MA) was inserted through a 20mm incision. After insufflation of the abdomen with CO2 gas, a 5-mm flexible laparoscope (Olympus Surgical, Tokyo, Japan) was introduced. Surgical procedures were performed using bent laparoscopic instruments (Roticulator, Endo MiniShears, and Opti4; Covidien). In the case of a right-sided tumor, we also used a 2-mm miniport to lift up the liver. The hospital and operative charts of these patients were reviewed retrospectively, and the patient characteristics and the immediate surgical outcomes were analyzed and compared in all patients. When a record indicated ‘‘minimal
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blood loss,’’ blood loss was estimated at 30 mL for each procedure. In every patient, the preoperative and intraoperative hemodynamic variables, including serum and urinary data, were compared. A ‘‘hypertensive episode’’ was defined as systolic blood pressure (SBP) that increased 30% above the baseline or SBP of 200 mm Hg or higher, and a ‘‘hypotensive episode’’ was defined as SBP that decreased below 80 mm Hg. With respect to heart rate, the number of tachycardic (110 beats per minute or greater) episodes was recorded. Postoperative complications within 1 month after an operation were checked in every patient, and classified according to Clavien-Dindo’s classification.9 The study was approved by the Institutional Review Board of Keio University Hospital. Statistical analyses were performed using a commercially available program (SPSS version 20.0 software for Windows, Chicago, IL). The clinical and surgical results were examined using the Mann-Whitney U test and w2-test for continuous and categorical variables, respectively. Cox proportional hazard regression models were used for univariate and multivariate analyses to test the relationships between prolonged operation time and perioperative factors. To obtain a multivariate model with maximum precision for the important variables, a stepwise selection procedure was used. All P values were two sided, and P < 0.05 was considered significant. Results
The mean follow-up for all patients was 44.2 months (1– 140 months). Two patients with PCC and one patient with PGL were found to have mutations in the multiple endocrine dysplasia type 2 gene. No recurrence or metastasis was observed during the follow-up period.
Table 1. Patient Background P Pheochromocytoma Paraganglioma value* No. patients Age Sex: Male Female BMI (kg/m2) Surgical procedure: LESS surgery Conventional Side of adrenalectomy: Right Left ASA-PS grade: ‡3 £2 Preoperative history: Yes No Tumor size (mm)
49 50.9 – 13.3
9 49.7 – 16.1
22 27 21.9 – 3.4
4 5 21.7 – 2.1
19 30
3 6
0.834 1.000 0.838
0.718 18 31
4 5
10 39
2 7
1.000 0.422 14 35 45.4 – 23.2
1 8 35.7 – 13.6
0.273
*Mann-Whitney U test and v2 -test. ASA-PS = American Society of Anesthesiologists Physical Status; BMI = body mass index; LESS = laparoendoscopic single-site.
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Table 2. Perioperative Data P Pheochromocytoma Paraganglioma value* No. patients 49 Operative 149.4 – 56.5 time (min) Pneumoperitoneum 116.4 – 54.4 time (min) Intraoperative 48.8 – 66.8 blood loss (mL) Postoperative 6.0 – 1.1 hospital stay (d) Transfusion 0 Intraoperative 1 complication Conversion 1 (LESS to conventional) 1 (2.0%) Postoperative complications ‡ Clavien grade II
Table 3. Statistical Analysis of Factors Predicting Prolonged Operation Time ( ‡180 minutes) Multivariate
9 189.8 – 44.9
0.019
Variable
155.2 – 43.2
0.013
Preoperative history: Yes No Sex: Male Female BMI (kg/m2): < 25 ‡ 25 Tumor side: Left Right Tumor size (mm): < 50 ‡ 50
0.089
Tumor type: Pheochromocytoma Paraganglioma
0.041
ASA score: £2 ‡3 Preoperative urine norepinephrine (mg/d): ‡ 120 < 120 Preoperative urine epinephrine (mg/d): ‡ 23 < 23 Preoperative urine VMA (mg/mg Cr): ‡ 6.3 < 6.3
0.507
404.9 – 1036.3 0.257 9.4 – 6.8
0.174
1 1
0.289
1 (open conversion) 2 (22.2%)
0.289 0.012
*Mann-Whitney U test and v2 -test. d = days; LESS = laparoendoscopic single-site; min = minutes.
The preoperative patient characteristics are summarized in Table 1. Each group was equivalent with respect to age, sex, and body mass index. The mean size of the tumors was 43.9 – 22.2 mm, and there was no significant difference between the PCC and PGL groups (45.4 – 23.2 mm v 35.7 – 13.6 mm; P = 0.273). Table 2 presents the intraoperative and postoperative surgical outcomes. The mean operative time was 155.7 – 56.5 minutes; it was significantly longer in the PGL group (149.4 – 56.5 minutes v 189.8 – 44.9 minutes; P = 0.019). The mean pneumoperitoneum time was 122.5 – 54.4 minutes; it was significantly longer in the PGL group (116.4 – 54.4 minutes v 155.2 – 43.2 minutes; P = 0.013). There was no significant difference between the two groups in estimated blood loss, postoperative hospital stay, or intraoperative morbidity. Conversion to conventional laparoscopic surgery (from LESS surgery) was necessary in one PCC case, and open conversion and intraoperative transfusion were needed in one PGL case. One complication classified as Clavien grade II or higher (hypoglycemia, grade II) was observed in a PCC patient. Two postoperative complications classified as Clavien grade II or higher (renal infarction, DVT, and blood transfusion, grade II; catecholamine-induced heart failure, grade IV-a) were observed in the PGL group, and the difference between the two groups was statistically significant (PCC v PGL: 1 [2.0%] v 2 [22.2%]; P = 0.012). Table 3 presents the results of a statistical analysis of preoperative factors that predict prolonged operation time. In univariate analysis, tumor size ‡ 50 mm (P = 0.005) and PGL (P = 0.041) were statistically significant factors that predicted prolonged operative time. In multivariate analysis, tumor size ‡ 50 mm (P = 0.004) and PGL (P = 0.013) were also statistically significant factors that predicted prolonged operative time. Table 4 summarizes the medical history, preoperative medical treatment, SBP, and the levels of preoperative catecholamines, urinary catecholamines, and catecholamine metabolites in patients in the PCC and PGL groups. These
Univariate P value
Odds ratio (95% CI)
P value*
1.000 1.000 0.418 0.005
0.004 1 8.99 (2.02–39.93) 0.013 1 9.35 (1.59–54.91)
0.562
0.260
0.122
ASA = American Society of Anesthesiologists; BMI = body mass index; CI = confidence interval; Cr = creatinine; d = day; VMA = vanillylmandelic acid; y = year. *v2–test and logistic regression analysis.
preoperative hemodynamic variables did not differ between the two groups. The intraoperative hemodynamic status of the two groups is shown in Table 5. There was no significant difference in terms of the highest intraoperative blood pressure (173.8 – 38.6 mm Hg v 169.2 – 32.2 mm Hg, P = 0.742) or hypertensive episodes including SBP ‡ 200 mm Hg or ‡ 30% above the baseline (30 cases in the PCC group v 6 cases in the PGL group; P = 1.000). Intraoperative hypotension occurred in 15 PCC patients and in 8 PGL patients, and the difference was statistically significant (P = 0.002). There were no treatment-resistant hemodynamic changes that caused serious consequences. Seven patients in the PCC group and two patients in the PGL group needed continuous catecholamine injection for more than 24 hours postoperatively. There was no statistically significant difference between the two groups with respect to the maximum change
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Table 4. Preoperative Hemodynamic Variables
No. patients Medical history (n): Hypertension Diabetes mellitus Coronary artery disease Preoperative medications (n): a-blocker b-blocker Calcium channel antagonist Preoperative medication period (a-blocker: days): Mean preoperative data: SBP (mm Hg) Preoperative serum hormone: Norepinephrine (ng/mL) Epinephrine (ng/mL) Dopamine (ng/mL) Preoperative urinary hormone: Norepinephrine (lg/d) Epinephrine (lg/d) Dopamine (lg/d) Metanephrine (mg/d) VMA (lg/mg Cr)
Pheochromocytoma
Paraganglioma
P value*
49
9
26 9 3
4 2 0
0.726 1.000 1.000
42 28 18 53.5 – 30.9
6 5 2 40.0 – 32.4
0.177 1.000 0.476 0.469
121.2 – 17.7
118.1 – 11.5
0.616
1.91 – 2.61 0.18 – 0.25 0.04 – 0.04
1.42 – 1.03 0.43 – 1.04 0.04 – 0.04
0.583 0.140 0.702
567.1 – 798.1 124.6 – 222.0 1075.3 – 1416.6 1.77 – 3.87 11.32 – 11.12
499.9 – 354.7 136.7 – 301.2 839.5 – 423.0 1.26 – 1.81 8.16 – 5.42
0.817 0.893 0.645 0.718 0.467
*Mann-Whitney U test and v2-test. Cr = creatinine; d = day; SBP = systolic blood pressure; VMA = vanillylmandelic acid.
was 58 mm, and tight adhesion around the tumor was observed; therefore, we added two additional ports. The operation was successful and completed uneventfully.
in intraoperative blood pressure (90.8 mm Hg v 103.7 mm Hg; P = 0.378). Table 6 shows the patient backgrounds and perioperative outcomes in patients who underwent LESS surgery. There were no statistically significant differences in patient background or perioperative outcomes, including operative time, conversion ratio, and morbidity between the two groups. One PCC patient, a 59-year-old woman with a past history of hypertension and severe diabetes mellitus, required two additional ports intraoperatively. Her body mass index was 20.8, and she had no past history of surgery. The tumor size
Discussion
PCC and PGL are rare catecholamine-secreting tumors with an incidence in adults of about 2–8/100,000. Approximately 10% of PCC appear extra adrenal and are defined as PGL.10 The therapy of choice in PCC and PGL is surgery. During open surgery for PCC, serum catecholamine levels
Table 5. Intraoperative Hemodynamic Variables
No. patients Mean intraoperative data: Highest SBP (mm Hg): ‡ 200 mm Hg (cases) ‡ 30% up (cases) Lowest SBP (mm Hg): < 80 mm Hg (cases) Blood pressure change (mm Hg): ‡ 90 mm Hg (cases) Highest heart rate (bpm): ‡ 110 bpm (cases) Intraoperative vasoactive drugs (n) Intraoperative vasodilatatory drugs (n) Nitroprusside a-blocker b-blocker Calcium channel antagonist *Mann-Whitney U test and v2-test. bpm = beats per minute; SBP = systolic blood pressure.
Pheochromocytoma
Paraganglioma
P value*
49
9
173.8 – 38.6 17 30 82.9 – 12.4 15 90.8 – 44.3 23 89.1 – 20.9 8 45
169.2 – 32.2 2 6 68.9 – 10.5 8 103.7 – 38.0 7 98.9 – 21.8 3 9
0.897 0.137 1.000 0.003 0.002 0.378 0.147 0.206 0.350 1.000
8 42 28 18
3 6 5 2
0.350 0.177 1.000 0.476
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Table 6. Patient Perioperative Parameters (LESS Surgery)
No. patients Age Sex: Male Female BMI (kg/m2) Side of adrenalectomy: Right Left ASA-PS grade: ‡3 £2 Past operative history: Yes No Operative time (min) Pneumoperitoneum tissue (min) Intraoperative blood loss (mL) Postoperative hospital stay (d) Transfusion Intraoperative complication Conversion Postoperative complications (Clavien system): £ grade II ‡ grade III Tumor size (mm)
Pheochromocytoma
Paraganglioma
19 52.5 – 12.6
3 42.0 – 13.4
10 9 21.5 – 2.6
2 1 21.8 – 3.3
7 12
0 3
2 17
1 2
7 12 136.2 – 55.9 102.7 – 53.9 38.4 – 20.6 5.9 – 1.3 0 1 1 (LESS to conventional)
0 3 161.0 – 54.3 131.7 – 49.4 88.7 – 98.1 9.7 – 7.2 0 0 0
0 (0%) 0 (0%) 36.0 – 19.5
0 (0%) 1 (33.3%) 32.3 – 17.2
P value* 0.196 1.000 0.857 0.523 0.371 0.523 0.265 0.226 0.586 0.523
1.000 0.136 0.762
*Mann-Whitney U test and v2-test. ASA = American Society of Anesthesiologists; BMI = body mass index; d = day; LESS = laparoendoscopic single-site.
are reported to elevate by 1000-fold, which causes intraoperative hypertensive crisis and intraoperative morbidity.11 Some studies in recent decades have demonstrated smaller increases in plasma catecholamine levels and benefits in perioperative outcomes, and laparoscopic surgery has been widely considered to be the gold standard treatment in patients with adrenal PCC. These benefits were ascribed to the less traumatic nature of laparoscopic dissection. Experiences with minimally invasive excision of retroperitoneal PGL are still limited, however.8,12 Walz and associates reported 161 cases of PCC and PGL laparoscopic resections.12 Twenty-seven PGL were resected, but their report did not focus on the details of the surgical outcomes between the two groups. Recently, Goers and colleagues reported 15 cases of PGL (6 open, 9 laparoscopic) and compared them with 62 cases of PCC that were resected laparoscopically; they concluded that PGL could be safely resected laparoscopically despite the long operative times.8 Nevertheless, they did not discuss detailed intraoperative hemodynamic changes in these two groups. So in the current study, we tried to compare the surgical outcome of laparoscopic surgery, including LESS surgery, in patients with PCC and patients with PGL, paying attention not only to immediate postoperative outcomes but also to the intraoperative hemodynamic changes. A previous retrospective study that evaluated the perioperative outcomes of PCC and PGL concluded that large tumor size, prolonged duration of anesthesia, and increased levels of perioperative urinary catecholamine/catecholamine
metabolites were univariately associated with postoperative morbidity.13 In the current study, there was no statistical difference between the PCC and PGL groups with respect to tumor size and perioperative urinary catecholamine/catecholamine metabolites (Tables 1 and 4). Operative time and pneumoperitoneum time were both significantly longer in the PGL group. PGL and tumor size S50 mm were statistically significant factors that prolonged operation time (Table 3), and this result was in accordance with that of a previous report.8 Among intraoperative hemodynamic variables, although the intraoperative change in blood pressure was not significantly different between the two groups (PCC v PGL: 90.8 mm Hg v 103.7 mm Hg; P = 0.514), the lowest SBP was significantly lower in the PGL group (82.9 mm Hg v 68.9 mm Hg; P = 0.004). Postoperative morbidity was higher in the PGL group. These differences in hemodynamic changes and perioperative outcomes may be partly due to a number of challenges in removing PGLs, including the diversity in their location, greater difficulty in operative exposure, and proximity to other major structures, including the aorta, vena cava, renal vessels, and ureter. To our knowledge, there are few reports that discuss the surgical outcome of LESS surgery for PGL, and the feasibility of this surgery for PGL is controversial. In this series, LESS surgery was completed in 22 cases (Table 6). Compared with conventional laparoscopic surgery, LESS surgery for an adrenal tumor may have the advantages of decreased postoperative pain, shorter hospital stay, and improved cosmetics.7,14 With respect to difficulty of handling, we have
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previously reported that LESS surgery for adrenal tumors enables a greater tendency to manipulate tumors than laparoscopic surgery.15 Thus, we expected the higher morbidity and significant intraoperative change in blood pressure between the two groups. In the current study, however, the total postoperative morbidity for LESS surgery was 4.5%, and no case of PGL required conversion to conventional laparoscopic surgery. This result may imply the feasibility of LESS for PGL, but further evaluation is warranted in order to arrive at a definite conclusion. For many years it has been generally accepted that adrenal minimally invasive procedures should be restricted to benign tumors. This cannot be applied to cases of PCC and PGL because their biological behavior in nonmetastatic stages is unknown and cannot be identified unless relapse occurs. According to previous reports, perioperative factors including tumor size, do not reliably predict the malignancy of PCC.16,17 PGL has been reported to have an increased rate of malignancy compared with PCC.17,18 Van Heerden and colleagues described six patients who developed recurrent PCC at intervals of 5–13 years after the initial adrenalectomy.19 Similarly, Van Slycke et al reported local regional recurrence of PGL in 7 of 51 patients (13.7%).20 The Kaplan-Meier estimated incidence of recurrence in that series was 15% at 7 years and 23% after 10 years. In the current study, we did not observe any local recurrence in PCC and PGL patients, but the mean follow-up was 44.2 months. Our results show the short-term feasibility of laparoscopic surgery, including LESS surgery, for PCC and PGL; however, based on previous observations, consecutive follow-up for these patients is required. The main limitations of the present study were the small number of patients and the nonrandomization. The selection of surgical procedure (LESS or conventional laparoscopic surgery) was conducted according to the preference of the surgeon, and this would add selection bias. Also, because a perioperative complication occurred in only three cases and the number of LESS surgeries for PGL was only three, the outcomes might not be clinically significant. Nevertheless, we believe our findings provide valuable insight into the value of the surgical outcome of retroperitoneal PGL. Welldesigned prospective comparison studies are needed in order to draw additional conclusions. Conclusion
These results demonstrate that solitary retroperitoneal PGL could be resected safely under laparoscopic surgery, including LESS surgery. The PGL group needed a longer operative time, had more hypotensive episodes, and had higher postoperative morbidity than the PCC group. Though the perioperative outcome of LESS surgery for PGL is comparable to that of PCC, we should treat the patients with PGL accordingly. Disclosure Statement
No competing financial interests exist.
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References
1. Inabnet WB, Pitre J, Bernard D, Chapuis Y. Comparison of the hemodynamic parameters of open and laparoscopic adrenalectomy for pheochromocytoma. World J Surg 2000;24:574–578. 2. Sprung J, O’Hara JF, Jr., Gill IS, Abdelmalak B, Sarnaik A, Bravo EL. Anesthetic aspects of laparoscopic and open adrenalectomy for pheochromocytoma. Urology 2000;55: 339–343. 3. Zacharias M, Haese A, Jurczok A, Stolzenburg JU, Fornara P. Transperitoneal laparoscopic adrenalectomy: Outline of the preoperative management, surgical approach, and outcome. Eur Urol 2006;49:448–459. 4. Guazzoni G, Cestari A, Montorsi F, et al. Current role of laparoscopic adrenalectomy. Eur Urol 2001;40:8–16. 5. Kercher KW, Park A, Matthews BD, Rolband G, Sing RF, Heniford BT. Laparoscopic adrenalectomy for pheochromocytoma. Surg Endosc 2002;16:100–102. 6. Flavio Rocha M, Faramarzi-Roques R, Tauzin-Fin P, Vallee V, Leitao de Vasconcelos PR, Ballanger P. Laparoscopic surgery for pheochromocytoma. Eur Urol 2004;45:226– 232. 7. Lin VC, Tsai YC, Chung SD, et al. A comparative study of multiport versus laparoendoscopic single-site adrenalectomy for benign adrenal tumors. Surg Endosc 2012;26: 1135–1139. 8. Goers TA, Abdo M, Moley JF, Matthews BD, Quasebarth M, Brunt LM. Outcomes of resection of extra-adrenal pheochromocytomas/paragangliomas in the laparoscopic era: A comparison with adrenal pheochromocytoma. Surg Endosc 2013;27:428–433. 9. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–213. 10. Fishbein L, Nathanson KL. Pheochromocytoma and paraganglioma: Understanding the complexities of the genetic background. Cancer Genet 2012;205:1–11. 11. Kinney MA, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth 2002;16:359–369. 12. Walz MK, Alesina PF, Wenger FA, et al. Laparoscopic and retroperitoneoscopic treatment of pheochromocytomas and retroperitoneal paragangliomas: Results of 161 tumors in 126 patients. World J Surg 2006;30:899–908. 13. Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000;91:1118– 1123. 14. Tunca F, Senyurek YG, Terzioglu T, Iscan Y, Tezelman S. Single-incision laparoscopic adrenalectomy. Surg Endosc 2012;26:36–40. 15. Ishida M, Miyajima A, Takeda T, Hasegawa M, Kikuchi E, Oya M. Technical difficulties of transumbilical laparoendoscopic single-site adrenalectomy: Comparison with conventional laparoscopic adrenalectomy. World J Urol 2013;31:199–203. 16. Laird AM, Gauger PG, Doherty GM, Miller BS. Paraganglioma: Not just an extra-adrenal pheochromocytoma. Langenbecks Arch Surg 2012;397:247–253.
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17. Shen WT, Sturgeon C, Clark OH, Duh QY, Kebebew E. Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas. Surgery 2004;136:1129– 1137. 18. Proye C, Vix M, Goropoulos A, Kerlo P, Lecomte-Houcke M. High incidence of malignant pheochromocytoma in a surgical unit. 26 cases out of 100 patients operated from 1971 to 1991. J Endocrinol Invest 1992;15:651– 663. 19. van Heerden JA, Roland CF, Carney JA, Sheps SG, Grant CS. Long-term evaluation following resection of apparently benign pheochromocytoma(s)/paraganglioma(s). World J Surg 1990;14:325–329. 20. Van Slycke S, Caiazzo R, Pigny P, et al. Local-regional recurrence of sporadic or syndromic abdominal extraadrenal paraganglioma: Incidence, characteristics, and outcome. Surgery 2009;146:986–992.
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Address correspondence to: Akira Miyajima, MD, PhD Department of Urology Keio University School of Medicine 35 Shinanomachi, Shinjuku-ku Tokyo 160-8582 Japan E-mail: [email protected] Abbreviations Used CT ¼ computed tomography LESS ¼ laparoendoscopic single-site MRI ¼ magnetic resonance imaging PCC ¼ pheochromocytoma PGL ¼ paraganglioma SBP ¼ systolic blood pressure
Surgical Outcome of Laparoscopic Surgery, Including Laparoendoscopic Single-Site Surgery, for Retroperitoneal Paraganglioma Compared with Adrenal Pheochromocytoma Seiya Hattori, MD,1 Akira Miyajima, MD, PhD,1 Yousuke Hirasawa, MD,1 Eiji Kikuchi, MD, PhD,1 Isao Kurihara, MD, PhD,2 Kazutoshi Miyashita, MD, PhD,2 Hirotaka Shibata, MD, PhD,3 Ken Nakagawa, MD, PhD,1 and Mototsugu Oya, MD, PhD1
Abstract
Objective: Paraganglioma (PGL) is a rare type of tumor that arises from the extra-adrenal paraganglia. A PGL tumor hypersecretes catecholamines and causes symptoms identical to those in patients with hyper-functioning adrenal pheochromocytoma (PCC). In this study, we compared the surgical outcome of laparoscopic surgery, including laparoendoscopic single-site (LESS) surgery, in patients with PCC and patients with retroperitoneal solitary PGL. Methods: The records of 49 patients with PCC and 9 patients with unilateral retroperitoneal PGL at our institution from January 2001 to March 2013 were retrospectively reviewed. Multiple tumors, tumors suspected of being malignant preoperatively, and tumors operated on using a retroperitoneal approach were excluded from the study. Results: Each group was equivalent with respect to patient background, hemodynamic variables, and preoperative biochemical assessments, including plasma catecholamine levels and catecholamine levels in 24-hour urine samples. The mean operative time was significantly longer in the PGL group (149.4 – 56.5 minutes v 189.8 – 44.9 minutes, P = 0.019). In univariate and multivariate analyses, tumor size ‡ 50 mm and PGL were statistically significant factors that predicted prolonged operative time. Intraoperative hypotension occurred in 15 patients in the PCC group and in 8 patients in the PGL group, and the difference was statistically significant (P = 0.002). One postoperative complication in the PCC group and two postoperative complications (Clavien-Dindo grade II or higher) in the PGL group were observed, and the difference was statistically significant (P = 0.012). Twenty-two patients in this series underwent LESS surgery (PCC: n = 19; PGL: n = 3), and there was no statistically significant difference in the perioperative outcomes between the two groups. Conclusions: The present results demonstrate that the operation for solitary extraperitoneal PGL required a longer operative time and had more hypotensive episodes and higher postoperative morbidity than the PCC group. Though the perioperative outcome of LESS surgery for PGL is comparable to that of PCC, we should treat the patients with PGL accordingly.
Introduction
P
araganglioma (PGL) is a rare tumor that arises from extra-adrenal paraganglia. A PGL tumor hypersecretes catecholamines and causes symptoms identical to those in patients with hyper-functioning adrenal pheochromocytoma (PCC). The treatment of choice for both PCC and PGL is surgical resection, and most tumors are benign and can be completely excised. Since the first case of laparoscopic re-
moval of a PCC, there has been adequate discussion of the safety of performing laparoscopic surgery for PCC because of the increased morbidity and adverse hemodynamic sequel. Recently, many reports have indicated that laparoscopic surgery is superior to open surgery in patients with PCC in terms of postoperative pain, rapid convalescence, and short hospital stay if performed with careful hemodynamic monitoring.1–5 With recent advances in laparoscopic techniques, instrumentation, and anesthetics combined with
Departments of 1Urology and 2Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 3 Department of Endocrinology and Metabolism, Oita University, Oita, Japan.
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vastly improved preoperative imaging capabilities, laparoscopic surgery for adrenal PCC is widely considered to be the current gold standard approach.5–7 Operative time for laparoscopic surgery in PGL patients, however, is reported to be significantly longer than that of PCC,8 suggesting increased difficulty with laparoscopic surgery for PGL. As PGL is a rare type of tumor, only a few reports have investigated the surgical outcome of laparoscopic or laparoendoscopic single-site (LESS) surgery for retroperitoneal PGL compared with that of adrenal PCC, especially with respect to intraoperative hemodynamic changes and morbidity. The aim of this study was to compare the surgical outcome of laparoscopic surgery, including LESS surgery, in patients with PCC and patients with solitary, retroperitoneal abdominal PGL, paying attention not only to immediate postoperative outcomes but also to the intraoperative hemodynamic changes. Methods
Records of 62 consecutive patients with PCC or PGL who underwent unilateral laparoscopic adrenalectomy or retroperitoneal tumorectomy at our institution from January 2001 to March 2013 were entered into a database. Patients with a tumor suspected preoperatively of malignancy (n = 1; one PCC patient) and patients with insufficient perioperative data (n = 2; one PCC patient and one PGL patient) and/or a tumor operated on using a retroperitoneal approach (n = 1; one PCC patient) were excluded from the study. In the end, 49 patients with PCC and 9 patients with unilateral retroperitoneal PGL were included. All of the PGL were located in the perirenal hilum (n = 7) or para-aortic area (caudal to the renal vessels: n = 1; upper to the renal vessels: n = 1). Among these patients, 22 had undergone LESS surgery (PGL, n = 3: perirenal hilum, n = 2; para-aortic, caudal to the renal vessels, n = 1). a-adrenergic blockade was initiated at least 2 weeks before surgery, and b-adrenergic blockade was added in patients with coexisting tachycardia. All patients underwent CT, MRI, and/or 123iobenguane m-iodobenzylguanidine (123I mIBG) scintigraphy preoperatively. Preoperative biochemical assessments included the measurement of plasma catecholamine levels and catecholamine and metabolite levels in 24-hour urine samples. Surgical procedures were performed or supervised by two skilled laparoscopic surgeons (A. Miyajima and K. Nakagawa), who to date have performed more than 500 cases of urologic laparoscopic surgery together. All operations used a transperitoneal approach. The selection of surgical procedure (LESS or conventional laparoscopic surgery) was left to the surgeon’s preference. In LESS surgery, we operated through the umbilicus (14 cases) or beside the navel (8 cases). The multichannel port (SILS port, Covidien, Mansfield, MA) was inserted through a 20mm incision. After insufflation of the abdomen with CO2 gas, a 5-mm flexible laparoscope (Olympus Surgical, Tokyo, Japan) was introduced. Surgical procedures were performed using bent laparoscopic instruments (Roticulator, Endo MiniShears, and Opti4; Covidien). In the case of a right-sided tumor, we also used a 2-mm miniport to lift up the liver. The hospital and operative charts of these patients were reviewed retrospectively, and the patient characteristics and the immediate surgical outcomes were analyzed and compared in all patients. When a record indicated ‘‘minimal
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blood loss,’’ blood loss was estimated at 30 mL for each procedure. In every patient, the preoperative and intraoperative hemodynamic variables, including serum and urinary data, were compared. A ‘‘hypertensive episode’’ was defined as systolic blood pressure (SBP) that increased 30% above the baseline or SBP of 200 mm Hg or higher, and a ‘‘hypotensive episode’’ was defined as SBP that decreased below 80 mm Hg. With respect to heart rate, the number of tachycardic (110 beats per minute or greater) episodes was recorded. Postoperative complications within 1 month after an operation were checked in every patient, and classified according to Clavien-Dindo’s classification.9 The study was approved by the Institutional Review Board of Keio University Hospital. Statistical analyses were performed using a commercially available program (SPSS version 20.0 software for Windows, Chicago, IL). The clinical and surgical results were examined using the Mann-Whitney U test and w2-test for continuous and categorical variables, respectively. Cox proportional hazard regression models were used for univariate and multivariate analyses to test the relationships between prolonged operation time and perioperative factors. To obtain a multivariate model with maximum precision for the important variables, a stepwise selection procedure was used. All P values were two sided, and P < 0.05 was considered significant. Results
The mean follow-up for all patients was 44.2 months (1– 140 months). Two patients with PCC and one patient with PGL were found to have mutations in the multiple endocrine dysplasia type 2 gene. No recurrence or metastasis was observed during the follow-up period.
Table 1. Patient Background P Pheochromocytoma Paraganglioma value* No. patients Age Sex: Male Female BMI (kg/m2) Surgical procedure: LESS surgery Conventional Side of adrenalectomy: Right Left ASA-PS grade: ‡3 £2 Preoperative history: Yes No Tumor size (mm)
49 50.9 – 13.3
9 49.7 – 16.1
22 27 21.9 – 3.4
4 5 21.7 – 2.1
19 30
3 6
0.834 1.000 0.838
0.718 18 31
4 5
10 39
2 7
1.000 0.422 14 35 45.4 – 23.2
1 8 35.7 – 13.6
0.273
*Mann-Whitney U test and v2 -test. ASA-PS = American Society of Anesthesiologists Physical Status; BMI = body mass index; LESS = laparoendoscopic single-site.
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Table 2. Perioperative Data P Pheochromocytoma Paraganglioma value* No. patients 49 Operative 149.4 – 56.5 time (min) Pneumoperitoneum 116.4 – 54.4 time (min) Intraoperative 48.8 – 66.8 blood loss (mL) Postoperative 6.0 – 1.1 hospital stay (d) Transfusion 0 Intraoperative 1 complication Conversion 1 (LESS to conventional) 1 (2.0%) Postoperative complications ‡ Clavien grade II
Table 3. Statistical Analysis of Factors Predicting Prolonged Operation Time ( ‡180 minutes) Multivariate
9 189.8 – 44.9
0.019
Variable
155.2 – 43.2
0.013
Preoperative history: Yes No Sex: Male Female BMI (kg/m2): < 25 ‡ 25 Tumor side: Left Right Tumor size (mm): < 50 ‡ 50
0.089
Tumor type: Pheochromocytoma Paraganglioma
0.041
ASA score: £2 ‡3 Preoperative urine norepinephrine (mg/d): ‡ 120 < 120 Preoperative urine epinephrine (mg/d): ‡ 23 < 23 Preoperative urine VMA (mg/mg Cr): ‡ 6.3 < 6.3
0.507
404.9 – 1036.3 0.257 9.4 – 6.8
0.174
1 1
0.289
1 (open conversion) 2 (22.2%)
0.289 0.012
*Mann-Whitney U test and v2 -test. d = days; LESS = laparoendoscopic single-site; min = minutes.
The preoperative patient characteristics are summarized in Table 1. Each group was equivalent with respect to age, sex, and body mass index. The mean size of the tumors was 43.9 – 22.2 mm, and there was no significant difference between the PCC and PGL groups (45.4 – 23.2 mm v 35.7 – 13.6 mm; P = 0.273). Table 2 presents the intraoperative and postoperative surgical outcomes. The mean operative time was 155.7 – 56.5 minutes; it was significantly longer in the PGL group (149.4 – 56.5 minutes v 189.8 – 44.9 minutes; P = 0.019). The mean pneumoperitoneum time was 122.5 – 54.4 minutes; it was significantly longer in the PGL group (116.4 – 54.4 minutes v 155.2 – 43.2 minutes; P = 0.013). There was no significant difference between the two groups in estimated blood loss, postoperative hospital stay, or intraoperative morbidity. Conversion to conventional laparoscopic surgery (from LESS surgery) was necessary in one PCC case, and open conversion and intraoperative transfusion were needed in one PGL case. One complication classified as Clavien grade II or higher (hypoglycemia, grade II) was observed in a PCC patient. Two postoperative complications classified as Clavien grade II or higher (renal infarction, DVT, and blood transfusion, grade II; catecholamine-induced heart failure, grade IV-a) were observed in the PGL group, and the difference between the two groups was statistically significant (PCC v PGL: 1 [2.0%] v 2 [22.2%]; P = 0.012). Table 3 presents the results of a statistical analysis of preoperative factors that predict prolonged operation time. In univariate analysis, tumor size ‡ 50 mm (P = 0.005) and PGL (P = 0.041) were statistically significant factors that predicted prolonged operative time. In multivariate analysis, tumor size ‡ 50 mm (P = 0.004) and PGL (P = 0.013) were also statistically significant factors that predicted prolonged operative time. Table 4 summarizes the medical history, preoperative medical treatment, SBP, and the levels of preoperative catecholamines, urinary catecholamines, and catecholamine metabolites in patients in the PCC and PGL groups. These
Univariate P value
Odds ratio (95% CI)
P value*
1.000 1.000 0.418 0.005
0.004 1 8.99 (2.02–39.93) 0.013 1 9.35 (1.59–54.91)
0.562
0.260
0.122
ASA = American Society of Anesthesiologists; BMI = body mass index; CI = confidence interval; Cr = creatinine; d = day; VMA = vanillylmandelic acid; y = year. *v2–test and logistic regression analysis.
preoperative hemodynamic variables did not differ between the two groups. The intraoperative hemodynamic status of the two groups is shown in Table 5. There was no significant difference in terms of the highest intraoperative blood pressure (173.8 – 38.6 mm Hg v 169.2 – 32.2 mm Hg, P = 0.742) or hypertensive episodes including SBP ‡ 200 mm Hg or ‡ 30% above the baseline (30 cases in the PCC group v 6 cases in the PGL group; P = 1.000). Intraoperative hypotension occurred in 15 PCC patients and in 8 PGL patients, and the difference was statistically significant (P = 0.002). There were no treatment-resistant hemodynamic changes that caused serious consequences. Seven patients in the PCC group and two patients in the PGL group needed continuous catecholamine injection for more than 24 hours postoperatively. There was no statistically significant difference between the two groups with respect to the maximum change
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Table 4. Preoperative Hemodynamic Variables
No. patients Medical history (n): Hypertension Diabetes mellitus Coronary artery disease Preoperative medications (n): a-blocker b-blocker Calcium channel antagonist Preoperative medication period (a-blocker: days): Mean preoperative data: SBP (mm Hg) Preoperative serum hormone: Norepinephrine (ng/mL) Epinephrine (ng/mL) Dopamine (ng/mL) Preoperative urinary hormone: Norepinephrine (lg/d) Epinephrine (lg/d) Dopamine (lg/d) Metanephrine (mg/d) VMA (lg/mg Cr)
Pheochromocytoma
Paraganglioma
P value*
49
9
26 9 3
4 2 0
0.726 1.000 1.000
42 28 18 53.5 – 30.9
6 5 2 40.0 – 32.4
0.177 1.000 0.476 0.469
121.2 – 17.7
118.1 – 11.5
0.616
1.91 – 2.61 0.18 – 0.25 0.04 – 0.04
1.42 – 1.03 0.43 – 1.04 0.04 – 0.04
0.583 0.140 0.702
567.1 – 798.1 124.6 – 222.0 1075.3 – 1416.6 1.77 – 3.87 11.32 – 11.12
499.9 – 354.7 136.7 – 301.2 839.5 – 423.0 1.26 – 1.81 8.16 – 5.42
0.817 0.893 0.645 0.718 0.467
*Mann-Whitney U test and v2-test. Cr = creatinine; d = day; SBP = systolic blood pressure; VMA = vanillylmandelic acid.
was 58 mm, and tight adhesion around the tumor was observed; therefore, we added two additional ports. The operation was successful and completed uneventfully.
in intraoperative blood pressure (90.8 mm Hg v 103.7 mm Hg; P = 0.378). Table 6 shows the patient backgrounds and perioperative outcomes in patients who underwent LESS surgery. There were no statistically significant differences in patient background or perioperative outcomes, including operative time, conversion ratio, and morbidity between the two groups. One PCC patient, a 59-year-old woman with a past history of hypertension and severe diabetes mellitus, required two additional ports intraoperatively. Her body mass index was 20.8, and she had no past history of surgery. The tumor size
Discussion
PCC and PGL are rare catecholamine-secreting tumors with an incidence in adults of about 2–8/100,000. Approximately 10% of PCC appear extra adrenal and are defined as PGL.10 The therapy of choice in PCC and PGL is surgery. During open surgery for PCC, serum catecholamine levels
Table 5. Intraoperative Hemodynamic Variables
No. patients Mean intraoperative data: Highest SBP (mm Hg): ‡ 200 mm Hg (cases) ‡ 30% up (cases) Lowest SBP (mm Hg): < 80 mm Hg (cases) Blood pressure change (mm Hg): ‡ 90 mm Hg (cases) Highest heart rate (bpm): ‡ 110 bpm (cases) Intraoperative vasoactive drugs (n) Intraoperative vasodilatatory drugs (n) Nitroprusside a-blocker b-blocker Calcium channel antagonist *Mann-Whitney U test and v2-test. bpm = beats per minute; SBP = systolic blood pressure.
Pheochromocytoma
Paraganglioma
P value*
49
9
173.8 – 38.6 17 30 82.9 – 12.4 15 90.8 – 44.3 23 89.1 – 20.9 8 45
169.2 – 32.2 2 6 68.9 – 10.5 8 103.7 – 38.0 7 98.9 – 21.8 3 9
0.897 0.137 1.000 0.003 0.002 0.378 0.147 0.206 0.350 1.000
8 42 28 18
3 6 5 2
0.350 0.177 1.000 0.476
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Table 6. Patient Perioperative Parameters (LESS Surgery)
No. patients Age Sex: Male Female BMI (kg/m2) Side of adrenalectomy: Right Left ASA-PS grade: ‡3 £2 Past operative history: Yes No Operative time (min) Pneumoperitoneum tissue (min) Intraoperative blood loss (mL) Postoperative hospital stay (d) Transfusion Intraoperative complication Conversion Postoperative complications (Clavien system): £ grade II ‡ grade III Tumor size (mm)
Pheochromocytoma
Paraganglioma
19 52.5 – 12.6
3 42.0 – 13.4
10 9 21.5 – 2.6
2 1 21.8 – 3.3
7 12
0 3
2 17
1 2
7 12 136.2 – 55.9 102.7 – 53.9 38.4 – 20.6 5.9 – 1.3 0 1 1 (LESS to conventional)
0 3 161.0 – 54.3 131.7 – 49.4 88.7 – 98.1 9.7 – 7.2 0 0 0
0 (0%) 0 (0%) 36.0 – 19.5
0 (0%) 1 (33.3%) 32.3 – 17.2
P value* 0.196 1.000 0.857 0.523 0.371 0.523 0.265 0.226 0.586 0.523
1.000 0.136 0.762
*Mann-Whitney U test and v2-test. ASA = American Society of Anesthesiologists; BMI = body mass index; d = day; LESS = laparoendoscopic single-site.
are reported to elevate by 1000-fold, which causes intraoperative hypertensive crisis and intraoperative morbidity.11 Some studies in recent decades have demonstrated smaller increases in plasma catecholamine levels and benefits in perioperative outcomes, and laparoscopic surgery has been widely considered to be the gold standard treatment in patients with adrenal PCC. These benefits were ascribed to the less traumatic nature of laparoscopic dissection. Experiences with minimally invasive excision of retroperitoneal PGL are still limited, however.8,12 Walz and associates reported 161 cases of PCC and PGL laparoscopic resections.12 Twenty-seven PGL were resected, but their report did not focus on the details of the surgical outcomes between the two groups. Recently, Goers and colleagues reported 15 cases of PGL (6 open, 9 laparoscopic) and compared them with 62 cases of PCC that were resected laparoscopically; they concluded that PGL could be safely resected laparoscopically despite the long operative times.8 Nevertheless, they did not discuss detailed intraoperative hemodynamic changes in these two groups. So in the current study, we tried to compare the surgical outcome of laparoscopic surgery, including LESS surgery, in patients with PCC and patients with PGL, paying attention not only to immediate postoperative outcomes but also to the intraoperative hemodynamic changes. A previous retrospective study that evaluated the perioperative outcomes of PCC and PGL concluded that large tumor size, prolonged duration of anesthesia, and increased levels of perioperative urinary catecholamine/catecholamine
metabolites were univariately associated with postoperative morbidity.13 In the current study, there was no statistical difference between the PCC and PGL groups with respect to tumor size and perioperative urinary catecholamine/catecholamine metabolites (Tables 1 and 4). Operative time and pneumoperitoneum time were both significantly longer in the PGL group. PGL and tumor size S50 mm were statistically significant factors that prolonged operation time (Table 3), and this result was in accordance with that of a previous report.8 Among intraoperative hemodynamic variables, although the intraoperative change in blood pressure was not significantly different between the two groups (PCC v PGL: 90.8 mm Hg v 103.7 mm Hg; P = 0.514), the lowest SBP was significantly lower in the PGL group (82.9 mm Hg v 68.9 mm Hg; P = 0.004). Postoperative morbidity was higher in the PGL group. These differences in hemodynamic changes and perioperative outcomes may be partly due to a number of challenges in removing PGLs, including the diversity in their location, greater difficulty in operative exposure, and proximity to other major structures, including the aorta, vena cava, renal vessels, and ureter. To our knowledge, there are few reports that discuss the surgical outcome of LESS surgery for PGL, and the feasibility of this surgery for PGL is controversial. In this series, LESS surgery was completed in 22 cases (Table 6). Compared with conventional laparoscopic surgery, LESS surgery for an adrenal tumor may have the advantages of decreased postoperative pain, shorter hospital stay, and improved cosmetics.7,14 With respect to difficulty of handling, we have
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previously reported that LESS surgery for adrenal tumors enables a greater tendency to manipulate tumors than laparoscopic surgery.15 Thus, we expected the higher morbidity and significant intraoperative change in blood pressure between the two groups. In the current study, however, the total postoperative morbidity for LESS surgery was 4.5%, and no case of PGL required conversion to conventional laparoscopic surgery. This result may imply the feasibility of LESS for PGL, but further evaluation is warranted in order to arrive at a definite conclusion. For many years it has been generally accepted that adrenal minimally invasive procedures should be restricted to benign tumors. This cannot be applied to cases of PCC and PGL because their biological behavior in nonmetastatic stages is unknown and cannot be identified unless relapse occurs. According to previous reports, perioperative factors including tumor size, do not reliably predict the malignancy of PCC.16,17 PGL has been reported to have an increased rate of malignancy compared with PCC.17,18 Van Heerden and colleagues described six patients who developed recurrent PCC at intervals of 5–13 years after the initial adrenalectomy.19 Similarly, Van Slycke et al reported local regional recurrence of PGL in 7 of 51 patients (13.7%).20 The Kaplan-Meier estimated incidence of recurrence in that series was 15% at 7 years and 23% after 10 years. In the current study, we did not observe any local recurrence in PCC and PGL patients, but the mean follow-up was 44.2 months. Our results show the short-term feasibility of laparoscopic surgery, including LESS surgery, for PCC and PGL; however, based on previous observations, consecutive follow-up for these patients is required. The main limitations of the present study were the small number of patients and the nonrandomization. The selection of surgical procedure (LESS or conventional laparoscopic surgery) was conducted according to the preference of the surgeon, and this would add selection bias. Also, because a perioperative complication occurred in only three cases and the number of LESS surgeries for PGL was only three, the outcomes might not be clinically significant. Nevertheless, we believe our findings provide valuable insight into the value of the surgical outcome of retroperitoneal PGL. Welldesigned prospective comparison studies are needed in order to draw additional conclusions. Conclusion
These results demonstrate that solitary retroperitoneal PGL could be resected safely under laparoscopic surgery, including LESS surgery. The PGL group needed a longer operative time, had more hypotensive episodes, and had higher postoperative morbidity than the PCC group. Though the perioperative outcome of LESS surgery for PGL is comparable to that of PCC, we should treat the patients with PGL accordingly. Disclosure Statement
No competing financial interests exist.
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Address correspondence to: Akira Miyajima, MD, PhD Department of Urology Keio University School of Medicine 35 Shinanomachi, Shinjuku-ku Tokyo 160-8582 Japan E-mail: [email protected] Abbreviations Used CT ¼ computed tomography LESS ¼ laparoendoscopic single-site MRI ¼ magnetic resonance imaging PCC ¼ pheochromocytoma PGL ¼ paraganglioma SBP ¼ systolic blood pressure
