Is There a Role for Laparoscopic Adrenalectomy in Patients with Suspected Adrenocortical Carcinoma? A Critical Appraisal of the Literature
Authors
Affiliations
C. Jurowich1, M. Fassnacht2, 3, M. Kroiss2, T. Deutschbein2, C .- T. Germer1, J. Reibetanz1
1 Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
2 Endocrine Unit, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany 3 Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany
Key words
adrenocortical carcinoma laparoscopic surgery oncology
Abstract
▼
Adrenocortical carcinoma (ACC) is a rare endo- crine neoplasm and complete resection is the only treatment with curative intent for patients with nonmetastatic disease. It is highly debatable whether minimally invasive surgery is oncologi- cally equal to open procedures in these patients. This review summarizes the current knowledge on the feasibility and oncological effectiveness of laparoscopic surgery for ACC. Using a Pubmed search strategy covering the time period up until July 2012, we identified 568 original articles and reviews with the following search terms: “adrenal gland neoplasms” and “laparoscopy”, with restriction to patients over 18 years of age. Finally, 23 publications, including 6 “key stud- ies”, became the basis of this review. The key papers described 673 patients with localized
ACC, of whom 112 had laparoscopic surgery. Acknowledging the subjectivity of our personal view, we draw the following conclusions: 1) since all available studies are retrospective, a final judgment of laparoscopic surgery in ACC cannot be provided; 2) the surgical treatment of patients with (suspected) ACC should be lim- ited to specialized centers; and 3) For tumors of limited size (<10cm) without evidence of inva- siveness, laparoscopic adrenalectomy does not seem to be oncologically inferior to open surgery when performed in a state of the art manner and when oncological standards (margin-free resection, avoidance of tumor spillage) are respected. However, open adrenalectomy should still be regarded as standard treatment for ACC and laparoscopic surgery should be performed within a clinical trial or at least as an observa- tional study.
received 31.07.2012 accepted 30.11.2012
Bibliography
DOI http://dx.doi.org/ 10.1055/s-0032-1331743 Published online: January 11, 2013 Horm Metab Res 2013; 45: 130-136 @ Georg Thieme Verlag KG Stuttgart . New York ISSN 0018-5043
Correspondence C. Jurowich, MD
Department of General, Visceral, Vascular and Pediatric Surgery University Hospital of Würzburg Oberdürrbacher Straße 6 97080 Würzburg Germany
Tel .: +49/931/201 31172
Fax: +49/931/201 39994
jurowich_c@chirurgie. uni-wuerzburg.de
Introduction
▼
In adrenocortical carcinoma (ACC), complete resection of the primary tumor is the only treat- ment with curative intent and therefore, remains the therapy of choice in localized disease [1-3]. In recent years, an improved surgical and periop- erative management and the fact that an increas- ing number of ACC patients are treated in specialized centers may have contributed to an improved outcome in localized ACC [4]. However, overall prognosis still remains unfavorable.
During the 1990s, minimally invasive surgery became a standard therapy for many benign dis- eases such as gastroesophageal reflux disease or gallstones, etc. Along with a reduction in surgical access trauma, a better and faster wound healing and a shorter postoperative recovery are major advantages. Although it was possible to demon- strate oncological equivalence of minimally invasive surgery, for example, for colon cancer treatment,
minimally invasive procedures are far from being routine for all malignant diseases.
Since the first laparoscopic adrenalectomy per- formed by Gagner et al. in 1992 [5], this access technique has been optimized steadily and has gained worldwide acceptance, and has therefore, become the “gold standard” for benign lesions of the adrenal gland [6]. Although some studies have concluded that laparoscopic adrenalectomy is feasible even in malignant adrenal tumors [7- 10], the significance of such an approach in patients with ACC is still highly debatable [11]. Due to the low incidence of ACC, our knowledge concerning this disease is mainly based on retro- spective studies or recommendations from single experts. With the exception of the recently pub- lished FIRM-ACT trial investigating chemother- apy in advanced ACC [12], there are no randomized trials available for this rare disease. Since there are no generally accepted guidelines for the surgical therapy of ACC, patients are often
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treated according to the personal experience of the local sur- geon.
The main objective of this review was to assess the oncological effectiveness of minimally invasive surgery in patients with ACC.
Methods
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We conducted a systematic review of the literature searching the PubMed and Medline databases to identify all relevant arti- cles published in English between 1992 (first report of LA [5]) and October 2012. Search terms used included the MeSH terms “adrenal gland neoplasms” and “laparoscopy”, with restriction to patients older than 18 years of age. Review articles, letters, comments, case reports, and articles including less than 3 patients with laparoscopic approach to ACC were not selected for this review. A subsequent search was performed based on electronic links to related articles in the PubMed database, as well as by searching the reference lists of selected publications. Based on the title and abstract, all potentially relevant articles were obtained as full-text copies, and scrutinized thoroughly. The authors selected the articles to be included in this review and any discordance was resolved by discussion. When similar cohorts were described in several publications, only the most recently published study was included. The selection process of included studies is shown in · Fig. 1. All articles were analyzed with the main focus on oncological outcome (recurrence rate and disease related death) of laparoscopic surgery in ACC (in comparison to open surgery). Furthermore, technical feasibility and conversion to open surgery were investigated. Publications dealing with adjuvant therapy [13-15] or surgery for recurrent ACC [16, 17] are not covered.
For each aspect we summarized published results and formu- lated conclusions for clinical practice.
Results
▼
Appraisal of present data
The search and selection process retrieved 23 studies, of which 6 articles addressed “laparoscopic adrenalectomy (LA) vs. open adrenalectomy (OA)” as a major topic including 673 patients eli- gible for this review (“key studies”, ” Table 1). The remaining 17
568 articles identified in PubMed and Medline databases
490 considered not relevant based on title and/or abstract
78 potentially relevant full-text articles
Case Reports or Letters, n=10
<3 patients with ACC, n=29
Review Articles, n=8
Duplicate Publications, n=4
Oncological outcome not reported, n=4
23 full-text articles eligible for review
„Laparoscopic versus open surgery for ACC” as a major topic, n=6
„Laparoscopic versus open surgery for ACC” as a secondary topic, n=22
publications were (mainly) case series of laparoscopic adrenal- ectomy for ACC (“minor studies”, · Table 2).
Only few studies have addressed the surgical access technique specifically for ACC (LA vs. OA) whereas most series include dif- ferent adrenal tumor entities. Only a small percentage of those patients finally was diagnosed as ACC. Furthermore, data on oncologic follow-up are missing, preventing a proper statistical analysis (. Table 2). Therefore, it was not possible to draw any valid conclusions from these studies, and the results did not find consideration in this manuscript.
We identified only 6 studies [7,8,18-21] analyzing the value of minimally invasive surgery in ACC patients as a major topic. Again, these series present heterogeneous patient groups with relatively small sample sizes, were performed retrospectively, and are affected by a relevant referral and selection bias. New data are not available and cannot be expected in the near future, due to the rarity of the disease.
Oncologic outcome
All of the 6 key studies [7,8,18-22] including 673 patients reported information useful for the analysis of the oncologic outcome of LA vs. OA. Three larger series [7,8,21] concluded that LA in ACC patients is oncologically as effective as OA, whereas the 3 other studies [18-20] clearly recommended against laparoscopic surgery for ACC.
The study of Brix et al. [7] included 152 patients with a tumor size of ≤10cm (OA: median, 8cm vs. LA: median, 6.2cm; p<0.001) of which 35 underwent LA (12 conversions to open surgery) and 117 underwent OA. Tumor recurrence and perito- neal carcinomatosis was documented in 77% and 3% of patients after LA, and in 69% and 3% of patients after OA, respectively (differences not significant). One strong point of this study is the fact that 2 different statistical approaches were performed. In a matched pairs analysis, disease-specific and disease-free sur- vival did not differ between the LA and the OA group {hazard ratio (HR) for death: 0.79 [95% confidence interval (CI), 0.36- 1.72]; p=0.55; HR for recurrence: 1.07 (95% CI, 0.61-1.87); p=0.82}. Similarly, in a subsequent multivariate analysis includ- ing all 152 patients, survival was identical after LA or OA [HR for death: 0.98 (95% CI, 0.50-1.92); p=0.96; HR for recurrence: 0.91 (95% CI, 0.56-1.47); p=0.69]. The authors concluded that for localized ACC of limited size, survival after LA and OA is compa- rable when surgery is carried out by an experienced surgeon.
The study by Porpiglia et al. [8] involved 43 patients with stage I and II disease, the LA group consisted of 18 patients (0 conver- sions to open surgery). The median recurrence-free survival (OA: 18 months vs. LA: 23 months, p=0.8) and the percentage of patients still alive after a 3-year follow-up (OA: 84% vs. LA: 100%, p=0.3) was comparable for both groups. Furthermore, both groups did not differ in terms of patterns of recurrence, especially, no port-site or peritoneal recurrences were noted. Again, the authors concluded that for stage I and II disease, LA and OA may achieve comparable outcome, when “principles of surgical oncology are respected”.
A recent study of Lombardi et al. [21] reports on 126 patients who underwent open adrenalectomy and 30 patients who underwent minimally invasive adrenalectomy. The local recur- rence rate was 19% for open adrenalectomy and 21% for mini- mally invasive adrenalectomy (p=0.497). Distant metastases were detected in 31% of patients in the OA group and 17% in the LA group (p=not reported). The mean time to recurrence was 27±27 months in the OA group and 29+33 months in the LA
| Authors | Year | n (ACC) | Lap/ Conv | Median Tu-size (cm) lap/conv | Overall recurrence (%) lap/conv | Peritoneal carcino- matosis lap/conv (%) | Median TTR (months) lap/conv | Positive resection mar- gins (%) lap/conv | Local recurrence rate (%) lap/conv | Median follow- up (months) |
|---|---|---|---|---|---|---|---|---|---|---|
| Gonzalez et al. [18] | 2005 | 139 | 6/133 | 6/13 | 100/86 | 83/17 | n.r./13 | not clearly stated | 50/38 | 28 |
| Leboulleux et al. [19] | 2010 | 64 | 6/58 | 7/14 | peritoneal carcino- matosis: 67/27 | 67/27 | 20* | 17/36 | 34/72 | 35 |
| Porpiglia et al. [8] | 2010 | 43 | 18/25 | 9/10.5 | 50/64 | 0/0 | 23/18 | n.r. | 33/24 | 35 |
| Miller et al. [20] | 2010 | 88 | 17/71 | 7/12.3 | 63/65 | 18/11 | 9.6/19.2 | 50/18 | 25/20 | 36.5 |
| Brix et al. [7] | 2010 | 152 | 35/117 | 6.2/8 | 77/69 | 3/3 | 24.2/21.5 | 8.6/15.4 | 77/69 | 39.3 |
| Lombardi et al. [21] | 2012 | 156 | 30/127 | 7.3/9 | 26/38 | n.r. | 29/27 | 0/0 | 13/11 | 42 |
TTR: time to recurrence; n.r .: not reported
*Overall median interval of time between initial surgery and the occurrence of peritoneal carcinosis; ** 2-Year local relapse rate; *** Matched pairs
group (p=0.839). No significant differences were found between the 2 groups in terms of 5-year disease-free survival (38.3% vs. 58.2%) and 5-year overall survival rates (48% vs. 67%; p=0.200). Three other series [18-20] advise caution using LA in ACC patients. The analysis of Gonzalez et al. [18] included 170 patients (160 underwent surgery) with a median tumor size of 13 cm, of which 6 patients underwent LA (1 conversion due to hemorrhage, 1 tumor fracture during extraction) at an outside institution. After a median follow-up of 28 months, the rate of local recurrence and peritoneal carcinomatosis in the open sur- gery group was 35% and 8%, respectively. In contrast, all 6 patients after LA had recurrences (local recurrence in 50% of patients and peritoneal carcinomatosis in 83% of patients, p<0.0001). No patient experienced port-site recurrence. The authors concluded that, due to the high risk of peritoneal carci- nomatosis after LA, OA should be the standard procedure in patients with suspected ACC.
Miller et al. [20] performed a retrospective review of 88 ACC patients, of which 17 had undergone laparoscopic adrenalectomy at an outside institution. Median tumor size was 7.0cm (range: 4-14) and 12.3cm (range: 5-27) in patients after LA and OA, respectively. Mean time of follow-up was 36.5 months. Overall recurrence was comparable for either group (LA: 63% vs. OA: 65%, p=0.22). However, violation to the tumor capsula and positive resection margins were more frequent in the LA group (LA: 50% vs. OA: 18%, p<0.01). Consequently, mean time to first recurrence was significantly reduced in patients after LA (LA: 9.6 months vs. OA: 19.2 months, p<0.005). The authors concluded that LA should be avoided in patients with adrenal tumors suspicious for ACC. The analysis of Leboulleux et al. [19] included 64 patients after R0/Rx-resection for ACC with a median tumor size of 13.2 cm [LA: 6.9cm (range: 3.5-9.0) vs. OA: 13.7 cm (range: 4.0-33.0), p=0.006]. Fifty-eight patients had undergone OA and 6 under- went LA. Patients treated with LA had a significantly increased rate of peritoneal carcinomatosis, when compared with patients who had undergone OA [HR: 3.8 (95% CI, 1.2-12.3); p=0.016], and the surgical approach (LA vs. OA) was identified as the only risk factor significantly associated with the occurrence of perito- neal carcinomatosis.
How can these contrary findings in these studies be explained? First, it is important to consider that all of them are retrospective and therefore, prone to a selection bias. In the series reporting an increased risk of capsule violation, incomplete resection and peritoneal carcinomatosis after LA [18-20], none of these
patients had been operated at the reporting institution and most were referred to these centers only after recurrence, leading to overrepresentation of poor risk patients. In contrast, the majority of patients in the laparoscopic group in the series published by Porpiglia et al. had surgery at the reporting institution [8]. In the series by Brix et al., 45% of the patients in the LA group and 61% in the OA group (p=0.56) had documented recurrence when referred to the German ACC registry [7]. Therefore, we believe that no major selection bias has affected the results of this study.
Technical aspects of laparoscopic adrenalectomy for
ACC
In ACC patients, the only treatment with curative intent is com- plete surgery by means of a margin-free resection and avoidance of any violation to the tumor capsule or spillage of tumor cells. These aspects must be respected by any surgical approach. Below, all relevant aspects of minimally invasive oncologic sur- gery are addressed.
| Authors | No. of patients with ACC | Tumor size | Tumor stage | Resection status | Follow-up | Recurrences |
|---|---|---|---|---|---|---|
| Hobart et al. 2000 [34] | 4 | Median 8 cm | NR | NR | 9.9 months | no local or portside recurrences |
| Henry et al. 2002 [35] | 6 (incl. 2 conversions) | Median 7.7cm | 6 McFarlane II | NR | 8-83 months | 1 (liver metastases) 5 FOR |
| Kebebew et al. 2002 [36] | 5 | Median 6.6 cm (2.5-12 cm) | NR | R0 in all patients | 3.3 years (1-7 years) | 3 locoregional recurrence (2 local, 1 lymph node) 2 FOR |
| Castilho et al. 2003 [37] | 4 | <5 cm | NR | NR | 17 months (1-60 months) | no local recurrences or metas- tases |
| Moinzadeh et al. 2005 [38] | 6 | 3.6-9cm | NR | 3 negative margin, 1 fractured specimen, 2 NR | 26 months (1-69 months) | 4 (2 local recurrence, 1 lung metastases, 1 NR) 2 FOR |
| Palazzo et al. 2006 [39] | 3 | Mean 6.9 cm (6-8 cm) | NR | NR | 13-32 months | 1 recurrence (liver) 2 FOR |
| Lombardi et al. 2006 [40] | 4 (incl. 1 conversion) | Median 5.9 cm (2-10cm) | NR | 23 months (8-41 months) | 1 pelvic recurrence 3 FOR | |
| Lodin et al. 2007 [41] | 5 | 3.5-8 cm | NR | NR | up to 58 months | 1 (multiple metastases), 3 NR 1 FOR |
| Nocca et al. 2007 [42] | 4 | Median 8.5 cm (4-14cm) | McFarlane I-II | NR | 34 months | 1 lung metastases 3 FOR |
| Hemal et al. 2008 [43] | 5 | Median 7.8 cm | NR | "no capsular rupture" | 13-60 months | 3 metastatic disease 2 FOR |
| Liao et al. 2006 [44] | 4 | 5-8.5cm | NR | R0 in all patients | 6-38 months | 3 recurrences (1 local + mul- tiple metastases, 2 multiple metastases) 1 FOR |
| Parnaby et al. 2008 [45] | 3 | ca. 6 cm | NR | NR | 4 years | 3 FOR |
| Mellon et al. 2008 [46] | 3 | Mean 4.9±2.1 | NR | NR | 27.4 months (1-61 months) | 0 |
| Conzo et al. 2009 [47] | 8 | <4 to >6cm | NR | NR | NR | NR |
| Lupascu et al. 2011 [48] | 4 | 7.0-7.4cm | NR | NR | 28.9 months (4-58 months) | 3 died of systemic recurrences (12, 19, 21 months after LA) 1 alive after left hepatectomy for liver metastases at 33 months after LA |
| Gaujoux et al. 2011 [49] | 8 (incl. 4 conversions) | >6cm | NR | NR | Median 32 (53) months | converted patients: 1 local recurrence, 3 FOR all noncon- verted: FOR |
| Greco et al. 2011 [31] | 34 | NR | 20 stage I, 14 stage II (McFarlane- Sullivan) | R0 in all patients | NR | 1 port-site metastasis 33 NR |
FOR: Free of recurrence; NR: not reported
Tumor size
Concerning the technical feasibility of LA, tumor size is of major importance. Although in the larger studies [7,8,20] median tumor size of the LA group was smaller than that of the OA group (6.2-9.0 cm vs. 8.0-12.3 cm), tumor size is obviously larger than in most benign adrenal lesions. Lombardi et al. do not report any differences in tumor size between the 2 groups [21].
Miller et al. [20] evaluated the rate of tumor recurrence, the rate of positive resection margins, and tumor spillage subject to tumor size. In the laparoscopic group, no relationship between tumor size and the resection status or rate of tumor spillage was found. However, outcome was superior for all groups of patients (<6cm, 6-10cm, >10cm), after OA. The authors concluded that a minimally invasive approach is inappropriate in ACC, although statistical analyses were not performed, due to the small number of included patients.
Comment: The question, whether there is a threshold for tumor size above which a patient should be excluded from laparoscopic surgery remains unanswered by the current litera- ture. Since an intact tumor capsule is of key importance for oncologic resection but also histopathological workup, the size of the incision for complete retrieval increases with the size of the tumor. Therefore, if at all, only tumors ≤10cm appear as suitable for a laparoscopic approach.
Lymphadenectomy
The issue of lymph node dissection (LND) is not touched in any of the above studies. However, most recent data from our group suggest that loco-regional LND contributes to a more accurate tumor staging and is associated with an improved prognosis in patients with localized ACC. Loco-regional LND should therefore be considered as part of the surgical treatment in patients undergoing surgery for ACC [23].
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Comment: The recommendation of loco-regional LND in ACC is based on one retrospective study in (mainly) open adrenalec- tomy [23]. These results are the most accurate evidence on this issue available at present. Studies on laparoscopically performed LND in ACC are lacking. However, according to our own experi- ence and results from renal cell carcinoma [24], laparoscopic retroperitoneal LND is technically feasible (· Fig. 2).
Multivisceral resections
Up to one third ACC patients need a multivisceral resection [25]. Although such a procedure might be occasionally feasible by laparoscopy, current literature does not support such an approach. Therefore, a multivisceral resection requires open surgery.
Comment: We strongly advise against LA when preoperative imaging shows evidence of invasiveness.
Peritoneal carcinomatosis
Peritoneal carcinomatosis occurs in 4-15% of ACC patients and is mainly caused by an intraoperative spillage of tumor cells within the peritoneal cavity. Although Gonzales et al. and Leb- oulleux et al. [18,19] reported an increased rate of peritoneal carcinomatosis in patients after laparoscopic resection of ACC, this observation was not confirmed by some larger studies [7,8,21], when compared with open surgery (~ Table 1).
Comment: Regarding the risk of peritoneal carcinomatosis as a result of LA, current literature is inconclusive. However, ade- quate oncological outcome and low rates of peritoneal carcino- matosis after LA reported from specialized surgical centers should not serve as justification for less experienced surgeons to use this technique as well.
Conversion from laparoscopic to open surgery
It is known from laparoscopic surgery in other malignancies that conversion to open surgery is a negative prognostic factor [26]. Brix et al. [7] reported a conversion rate of 34%, which is fairly high, when compared to minimally invasive surgery for other cancer entities (e.g., laparoscopic colorectal surgery) [26]. Rea- sons for conversion were bleeding, adhesions, perforation, and technical difficulties. In the analysis by Brix et al. [7], conversion to open surgery was not associated with an inferior prognosis.
Comment: The reason for conversion should be taken into account: a diagnostic laparoscopy and an early conversion to open surgery without technical problems should not negatively affect prognosis.
Retroperitoneoscopic approach vs. transabdominal approach
Minimally invasive adrenalectomy can be performed via a transperitoneal (laparoscopic) or a retroperitoneoscopic access, the latter of which was introduced by Gaur et al. in 1992 [27]. In a series of 560 laparoscopic adrenalectomies, Walz et al. [28]
proved the technical feasibility of the retroperitoneoscopic access for benign lesions. A recent meta-analysis comparing laparoscopic and retroperitoneoscopic adrenalectomy reported no general difference in the short-term outcome; however, ret- roperitoneoscopic adrenalectomy might be beneficial in terms of the duration of the postoperative hospital stay [29]. For ACC, data regarding the route of the minimally-invasive approach (transabdominal vs. retroperitoneal) remain uncertain. In the series by Porpiglia et al. and Miller et al. [20,30], all laparoscopi- cally treated patients had a transabdominal access, and in the series by Brix et al. [7], only 2 of 35 patients underwent retro- peritoneal adrenalectomy. However, in a large series of laparo- scopic adrenalectomy from German urological centers, the transabdominal and retroperitoneal approaches were equally distributed between the 34 patients who had an ACC on final histology [31].
Comment: Even for benign lesions of the adrenal gland, a clear evidence-based recommendation for one or the other access routes cannot be given, even less for suspected ACC. A surgeon experienced in one of the techniques appears of higher impor- tance (see below) and the authors prefer the laparoscopic approach to the adrenal gland.
Perioperative results/surgical outcome
Due to the improved perioperative outcome of minimally inva- sive adrenalectomy, this access has become the treatment of choice for benign lesions of the adrenal gland. LA has proven beneficial in terms of postoperative pain, length of hospital stay, and cosmetic results [6].
Comment: Whether these results can be transferred to the minimally invasive surgery in ACC, cannot be answered by cur- rent literature. However, it is reasonable to assume that in the surgical treatment of malignant tumors, the perioperative out- come is not only determined by the access trauma, but substan- tially influenced by the recurrent disease, aggressiveness of the tumor, and the biological behavior of the disease itself.
Surgical volume
Almost all reviews and statements on this topic recommend that the surgical treatment of patients with (suspected) ACC should be limited to specialized centers, as patient prognosis is essen- tially determined by the quality of the primary operation. Few publications have focused on the impact of surgical volume on patient outcome [31-33]; however, the number of included ACC was too small to draw robust conclusion. Therefore, there is for- mally no strong evidence that the number of adrenalectomies performed per year improves patient prognosis.
Comment: Despite the limitations mentioned above, we also strongly support the recommendation to perform surgery for a potentially malignant adrenal tumor only in specialized centers. Thus, we propose that surgery for suspected ACC should be lim-
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ited to centers with >20 adrenalectomies (for benign and malig- nant disease together) per year (although we are aware of the arbitrariness of this cutoff). The beneficial effect of high-volume centers on prognosis is not only explained by the number (and appropriateness) of surgeries performed per year, but also by the multidisciplinary experience of the (high-volume) center.
Preoperative malignancy uncertain - how to proceed? From an adrenal surgeon’s point of view, there is an ongoing dis- cussion on how to approach a patient with a small adrenal lesion of uncertain malignancy. We have to admit that there is a double standard in the surgery of adrenal incidentalomas: Most sur- geons argue that adrenal lesions with a clear risk of malignancy should be removed by open surgery. However, most hormonally silent tumors are nowadays removed by minimally invasive sur- gery (although the only reason to do so is the perceived risk of malignancy).
Comment: Although we know that the available data cannot clearly answer this important question, it does justify perform- ing laparoscopic surgery on these patients, when (i) principles of surgical oncology are respected, and (ii) the surgeon/center is experienced in laparoscopic adrenalectomy.
Conclusion
▼
Surgical therapy of ACC and surgery of undetermined adrenal masses should only be performed in specialized centers, and an interdisciplinary team should develop an individual treatment strategy for each patient. Open surgery remains the standard approach for patients with a perceived ACC. However, LA for ACC of limited size (≤10 cm) seems technically and oncologically fea- sible in the hands of an experienced surgeon. Oncological stand- ards, such as the R0-resection, lymphadenectomy, and the avoidance of tumor spillage are mandatory.
Conflict of Interest
▼
The authors declare that they have no conflicts of interest in the authorship or publication of this contribution.
References
1 Fassnacht M, Libe R, Kroiss M, Allolio B. Adrenocortical Carcinoma: a clinician’s update. Nat Rev Endocrinol 2011; 7: 323-335
2 Libe R, Fratticci A, Bertherat J. Adrenocortical cancer: pathophysiol ogy and clinical management. Endocr Relat Cancer 2007; 14: 13-28
3 Lacroix A. Approach to the patient with adrenocortical carcinoma. J Clin Endocrinol Metab 2010; 95: 4812-4822
4 Fassnacht M, Johanssen S, Fenske W, Weismann D, Agha A, Beuschlein F, Fuhrer D, Jurowich C, Quinkler M, Petersenn S, Spahn M, Hahner S, Allolio B. Improved survival in patients with stage II adrenocortical carcinoma followed up prospectively by specialized centers. J Clin Endocrinol Metab 2010; 95: 4925-4932
5 Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromocytoma. N Engl J Med 1992; 327: 1033
6 Assalia A, Gagner M. Laparoscopic adrenalectomy. Br J Surg 2004; 91: 1259-1274
7 Brix D, Allolio B, Fenske W, Agha A, Dralle H, Jurowich C, Langer P, Mussack T, Nies C, Riedmiller H, Spahn M, Weismann D, Hahner S, Fas- snacht M. Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients. Eur Urol 2010; 58: 609-615
8 Porpiglia F, Fiori C, Daffara F, Zaggia B, Bollito E, Volante M, Berruti A, Terzolo M. Retrospective Evaluation of the Outcome of Open Versus Laparoscopic Adrenalectomy for Stage I and II Adrenocortical Cancer. Eur Urol 2010; 57: 873-878
9 Eto M, Hamaguchi M, Harano M, Yokomizo A, Tatsugami K, Naito S. Laparoscopic adrenalectomy for malignant tumors. Int J Urol 2008; 15: 295-298
10 Haleblian GE, Wilson C, Haddad D, Albala DM. Adrenocortical carci- noma: role of laparoscopic surgery in treatment. Expert Rev Anti- cancer Ther 2007; 7: 1295-1300
11 Porpiglia F, Miller BS, Manfredi M, Fiori C, Doherty GM. A debate on laparoscopic versus open adrenalectomy for adrenocortical carci- noma. Horm Cancer 2011; 2: 372-377
12 Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B, Group F-AS. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med 2012; 366: 2189-2197
13 Fassnacht M, Hahner S, Polat B, Koschker AC, Kenn W, Flentje M, Allolio B. Adjuvant radiation therapy of the tumor bed prevents local recur- rences in adrenocortical carcinoma. Exp Clin Endocrinol Diabet 2006; 114 (Suppl 1): S17 (abstract P01-003)
14 Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 2007; 356: 2372-2380
15 Sabolch A, Feng M, Griffith K, Hammer G, Doherty G, Ben-Josef E. Adju- vant and Definitive Radiotherapy for Adrenocortical Carcinoma. Int J Radiat Oncol Biol Phys 2010; 80: 1477-1484
16 Datrice NM, Langan RC, Ripley RT, Kemp CD, Steinberg SM, Wood BJ, Libutti SK, Fojo T, Schrump DS, Avital I. Operative management for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol 2012; 105: 709-713
17 Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Maaa Q, Jaaa W, Wil- lenberg HS, Beuschlein F, Fottner C, Brix D, Fenske W, Reibetanz J, Allo- lio B, Fassnacht M; on behalf of the German Adrenocortical Carcinoma Study Group. The role of surgery in the management of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab 2012, Nov 12 doi:10.1210/jc.2012-2559 [Epub ahead of print]
18 Gonzalez RJ, Shapiro S, Sarlis N, Vassilopoulou-Sellin R, Perrier ND, Evans DB, Lee JE. Laparoscopic resection of adrenal cortical carcinoma: a cau- tionary note. Surgery 2005; 138: 1078-1085 discussion 1085-1076
19 Leboulleux S, Deandreis D, Al Ghuzlan A, Auperin A, Goere D, Dromain C, Elias D, Caillou B, Travagli JP, De Baere T, Lumbroso J, Young J, Schlum- berger M, Baudin E. Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? Eur J Endocrinol 2010; 162: 1147-1153
20 Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. Laparoscopic resection is inappropriate in patients with known or sus- pected adrenocortical carcinoma. World J Surg 2010; 34: 1380-1385
21 Lombardi CP, Raffaelli M, De Crea C, Boniardi M, De Toma G, Marzano LA, Miccoli P, Minni F, Morino M, Pelizzo MR, Pietrabissa A, Renda A, Valeri A, Bellantone R. Open versus endoscopic adrenalectomy in the treatment of localized (stage I/II) adrenocortical carcinoma: Results of a multiinstitutional Italian survey. Surgery 2012; 152: 1158-1164
22 Bellantone R, Ferrante A, Raffaelli M, Boscherini M, Lombardi CP, Cru- citti F. Adrenal cystic lesions: report of 12 surgically treated cases and review of the literature. J Endocrinol Invest 1998; 21: 109-114
23 Reibetanz J, Jurowich C, Erdogan I, Nies C, Rayes N, Dralle H, Behrend M, Allolio B, Fassnacht M, German ACCsg. Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. Ann Surg 2012; 255: 363-369
24 Simmons MN, Kaouk J, Gill IS, Fergany A. Laparoscopic radical nephrec- tomy with hilar lymph node dissection in patients with advanced renal cell carcinoma. Urology 2007; 70: 43-46
25 Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, Sturgeon C. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer 2008; 113: 3130-3136
26 Jayne DG, Thorpe HC, Copeland J, Quirke P, Brown JM, Guillou PJ. Five- year follow-up of the Medical Research Council CLASICC trial of laparoscopically assisted versus open surgery for colorectal cancer. Br J Surg 2010; 97: 1638-1645
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
27 Gaur DD. Laparoscopic operative retroperitoneoscopy: use of a new device. J Urol 1992; 148: 1137-1139
28 Walz MK, Alesina PF, Wenger FA, Deligiannis A, Szuczik E, Petersenn S, Ommer A, Groeben H, Peitgen K, Janssen OE, Philipp T, Neumann HP, Schmid KW, Mann K. Posterior retroperitoneoscopic adrenalec- tomy - results of 560 procedures in 520 patients. Surgery 2006; 140: 943-948 discussion 948-950
29 Constantinides VA, Christakis I, Touska P, Palazzo FF. Systematic review and meta-analysis of retroperitoneoscopic versus laparoscopic adrenalectomy. Br J Surg 2012; 99: 1639-1648
30 Porpiglia F, Fiori C, Daffara F, Zaggia B, Bollito E, Volante M, Berruti A, Terzolo M. Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer. Eur Urol 2010; 57: 873-878
31 Greco F, Hoda MR, Rassweiler J, Fahlenkamp D, Neisius DA, Kutta A, Thuroff JW, Krause A, Strohmaier WL, Bachmann A, Hertle L, Popken G, Deger S, Doehn C, Jocham D, Loch T, Lahme S, Janitzky V, Gilfrich CP, Klotz T, Kopper B, Rebmann U, Kalbe T, Wetterauer U, Leitenberger A, Rassler J, Kawan F, Inferrera A, Wagner S, Fornara P. Laparoscopic adrenalectomy in urological centres - the experience of the German Laparoscopic Working Group. BJU Int 2011; 108: 1646-1651
32 Lombardi CP, Raffaelli M, Boniardi M, De Toma G, Marzano LA, Miccoli P, Minni F, Morino M, Pelizzo MR, Pietrabissa A, Renda A, Valeri A, De Crea C, Bellantone R. Adrenocortical carcinoma: effect of hospital volume on patient outcome. Langenbecks Arch Surg 2012; 397: 201-207
33 Hermsen IG, Kerkhofs TM, Butter G, Kievit J, van Eijck CH, Nieveen van Dijkum EJ, Haak HR. Surgery in adrenocortical carcinoma: Importance of national cooperation and centralized surgery. Surgery 2012; 152: 50-56
34 Hobart MG, Gill IS, Schweizer D, Sung GT, Bravo EL. Laparoscopic adrenalectomy for large-volume (> or=5cm) adrenal masses. J Endourol 2000; 14: 149-154
35 Henry JF, Sebag F, Iacobone M, Mirallie E. Results of laparoscopic adrenalectomy for large and potentially malignant tumors. World J Surg 2002; 26: 1043-1047
36 Kebebew E, Siperstein AE, Clark OH, Duh QY. Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg 2002; 137: 948-951 discussion 952-943
37 Castilho LN, Mitre AI, Arap S. Laparoscopic adrenal surgery in a Brazil- ian center. J Endourol 2003; 17: 11-18
38 Moinzadeh A, Gill IS. Laparoscopic radical adrenalectomy for malig- nancy in 31 patients. J Urol 2005; 173: 519-525
39 Palazzo FF, Sebag F, Sierra M, Ippolito G, Souteyrand P, Henry JF. Long- term outcome following laparoscopic adrenalectomy for large solid adrenal cortex tumors. World J Surg 2006; 30: 893-898
40 Lombardi CP, Raffaelli M, De Crea C, Bellantone R. Role of laparoscopy in the management of adrenal malignancies. J Surg Oncol 2006; 94: 128-131
41 Lodin M, Privitera A, Giannone G. Laparoscopic adrenalectomy (LA): keys to success: correct surgical indications, adequate preoperative preparation, surgical team experience. Surg Laparosc Endosc Percu- tan Tech 2007; 17: 392-395
42 Nocca D, Aggarwal R, Mathieu A, Blanc PM, Deneve E, Salsano V, Figueira G, Sanders G, Domergue J, Millat B, Fabre PR. Laparoscopic surgery and corticoadrenalomas. Surg Endosc 2007; 21: 1373-1376
43 Hemal AK, Singh A, Gupta NP. Whether adrenal mass more than 5 cm can pose problem in laparoscopic adrenalectomy? An evaluation of 22 patients. World J Urol 2008; 26: 505-508
44 Liao CH, Chueh SC, Lai MK, Hsiao PJ, Chen J. Laparoscopic adrenalec- tomy for potentially malignant adrenal tumors greater than 5 centim- eters. J Clin Endocrinol Metab 2006; 91: 3080-3083
45 Parnaby CN, Chong PS, Chisholm L, Farrow J, Connell JM, O’Dwyer PJ. The role of laparoscopic adrenalectomy for adrenal tumours of 6 cm or greater. Surg Endosc 2008; 22: 617-621
46 Mellon MJ, Sundaram CP. Laparoscopic adrenalectomy for pheochro- mocytoma versus other surgical indications. JSLS 2008; 12: 380-384
47 Conzo G, Tricarico A, Belli G, Candela S, Corcione F, Del Genio G, Ferulano GP, Giardiello C, Livrea A, Marzano LA, Porcelli A, Sperlongano P, Vincenti R, Palazzo A, De Martino C, Musella M. Adrenal incidentalomas in the laparoscopic era and the role of correct surgical indications: observa- tions from 255 consecutive adrenalectomies in an Italian series. Can J Surg 2009; 52: E281-E285
48 Lupascu C, Tarcoveanu E, Bradea C, Andronic D, Ursulescu C, Niculescu D. Laparoscopic adrenalectomy for large solid cortical tumours - is it appropriate? Chirurgia (Bucur) 2011; 106: 315-320
49 Gaujoux S, Bonnet S, Leconte M, Zohar S, Bertherat J, Bertagna X, Dous- set B. Risk factors for conversion and complications after unilateral laparoscopic adrenalectomy. Br J Surg 2011; 98: 1392-1399
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