Journal Pre-proof
Prise en charge d’une tumeur cortico-surrenalienne: impact du traitement chirurgical
Eric Mirallié Claire Blanchard Cécile Caillard Patrice Rodien Claire Briet Stéphanie Mucci Delphine Drui Antoine Hamy
Annales d’Endocrinologie Annals of Endocrinology
1
ESFE
| PII: | S0003-4266(19)30211-2 |
| DOI: | https://doi.org/doi:10.1016/j.ando.2019.09.001 |
| Reference: | ANDO 1139 |
| To appear in: | Annales d'Endocrinologie |
Please cite this article as: Mirallie E, Blanchard C, Caillard C, Rodien P, Briet C, Mucci S, Drui D, Hamy A, Prise en charge d’une tumeur cortico-surrenalienne: impact du traitement chirurgical, Annales d’Endocrinologie (2019), doi: https://doi.org/10.1016/j.ando.2019.09.001
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
@ 2019 Published by Elsevier.
Prise en charge d’une tumeur cortico-surrenalienne : impact du traitement chirurgical Adrenocortical carcinoma: impact of surgical treatment
Eric Miralliéa*, Claire Blanchardª, Cécile Caillardª, Patrice Rodienb, Claire Brietb, Stéphanie Mucci”, Delphine Druid, Antoine Hamy“
a Clinique de chirurgie digestive et endocrinienne, IMAD, Hôtel Dieu, CHU de Nantes, place Alexis Ricordeau, 44093 Nantes cedex 01, France
b Service d’endocrinologie diabétologie et nutrition, CHU d’Angers, rue Larrey, 49933 Angers cedex 9, France
” Service de chirurgie viscérale et endocrinienne, CHU d’Angers, rue Larrey, 49933 Angers cedex 9, France
d Service d’endocrinologie et maladies métaboliques, l’institut du thorax, Hôpital Laennec, CHU de Nantes, 44093 Nantes cedex 01, France
*auteur correspondant
Adresse e-mail : eric.mirallie@chu-nantes.fr
Déclaration de liens d’intérêts
Les auteurs déclarent ne pas avoir de lien d’intérêts.
Abstract
Compared to benign adrenal lesions, secreting or otherwise, malignant adrenocortical carcinoma is rare. Overall prognosis is poor, with <50% 5-year survival. Various prognostic factors have been identified, some tumor-related and others directly linked to surgical treatment. Surgery is the only possible curative treatment, and is decided upon in a multidisciplinary medical-surgical team meeting. Surgical approach (laparotomy vs. laparoscopy) remains a matter of debate. In the light of a recent literature search, the present review reassesses the prognostic criteria of surgical resection, the quality of which determines overall and recurrence-free survival.
Résumé
Les carcinomes cortico-surrénaliens malins sont plus rares que les lésions surrénales bénignes, que celles-ci soient hormono-sécrétantes ou non. Le pronostic global est sombre, avec un taux de survie de < 50 % à 5 ans. Différents facteurs pronostiques ont été identifiés : certains sont liés à la tumeur, d’autres sont directement liés au traitement chirurgical. La chirurgie est le seul traitement curatif possible et sa réalisation est décidée au sein d’une réunion de concertation pluridisciplinaire médico- chirurgicale. L’approche chirurgicale (laparotomie ou laparoscopie) reste sujette à la discussion. Suite à une analyse récente de la littérature scientifique, cette mise au point réévalue les critères pronostiques de la résection chirurgicale, dont la bonne qualité détermine la survie globale et sans récidive du patient.
Keywords: adrenalectomy; adrenocortical carcinoma; laparoscopy; laparotomy; prognosis
Mots clés : cortico-surrenalome ; laparoscopie ; laparotomie ; pronostic ; surrénalectomie
1. Introduction
Since the first publication on laparoscopic adrenalectomy by Gagner et al. [1] in 1992, minimally invasive adrenal surgery has flourished considerably. In 2018, it was clear to all surgeons that a small
secreting benign tumor must be resected by laparoscopy. With regard to these benign and/or small tumors, the only questions concern the type of laparoscopic surgery: robot-assisted, traditional or retroperitoneal [2-4]. These three techniques are equal and minimally invasive in their approaches.
The problem that now remains is choosing the approach for a malignant or potentially malignant tumor. [table 1]
The aim of this clarification is to try to define the best approach to this kind of tumor. First of all, we will define the criteria for a “good” surgery for a malignant or potentially malignant tumor before discussing the surgical approach.
To do this, we shall consider, in view of the recent literature, the problems of 1) resection margins and their impact, 2) the value of lymph node involvement and the impact of lymph node dissection, and 3) the need or not to resect neighboring organs. We shall look at 4) the surgery for recurrences and then 5) some comparative studies (laparotomy verses laparoscopy) in the literature.
2. Importance of Resection Margins
Margonis et al. [5] evaluated the impact of the surgical resection margin for patients who were treated for malignant adrenocortical carcinoma between 1993 and 2014 in 13 centers in the USA. This included 165 patients who underwent a curative operation (median age of 53 years (45-63 years old)). The sex ratio was 2:1 female to male. 74 patients (46.5%) had a tumor that exceeded the adrenal capsule. The median size was 11 cm (7.7-15.0). 128 had had a laparotomy and 34 (21%) had had minimally invasive surgery. 42 patients (25.4%) had complications, which were grade 1-2 in 69% of cases. After a median follow-up period of 22.9 months, 53.9% (89 patients) had had a recurrence. Among RO (microscopically complete resection) patients, 30.3% were alive without recurrence after five years compared to 13.8% among R1 (microscopically incomplete resection) patients (p=0.03). In a multivariate analysis, the invaded margin significantly reduced survival without recurrence (relative risk (RR): 1.71, CI: 1.05-2.78; p=0.03). After adjusting for other risk factors, only the N+ status remained a predictive factor for survival without recurrence (relative risk: 2.70, 95% CI: 1.04-6.99; p=0.04). The overall median survival was 86.3 months. The percentages for overall survival were 89.2%, 70.9%, and 57.7% after one, three, and five years, respectively. The RO patients had a median survival of 96.3 months and overall survival of 64.8% after five years, compared to 25.1 months and 33.8% for R1 patients (p<0.001 for the two results). In a multivariate analysis, only the presence of an invaded margin was a predictive factor of overall weak survival (relative risk: 2.22, 95% CI: 1.03-4.77; p=0.04).
Panjwani et al. [6] evaluated the results of a retrospective study on patients compiled from the National Cancer Database. This database includes around 70% of the new cancer cases in the USA. In total, 2,168 patients with an adrenocortical carcinoma were included between 2004 and 2013. 827 patients were evaluated after excluding patients who did not have an operation (631, 29%), T4 patients, patients whose resection extended to neighboring organs, patients with metastatic cancer, and those who were missing data. In a univariate analysis, the factors influencing overall survival were the lymph node status (this will be revisited), surgical margins, and the extent of the tumor. Patients with an invaded margin had a survival rate after five years of 16%, compared to 58% for those who had a clean margin. In a multivariate analysis, the lymph node status (relative risk: 3.02, p<0.001) and the positive margin (relative risk 2.06, p=0.048) had a significant value. It is clear that an R0 resection is an essential factor for a good prognosis.
3. Significance of Lymph Node Involvement
According the anatomic reviews lymphatic mapping of adrenal gland is difficult and complex. There are 2 principals drainage flows : posterior to the inferior veinacaval and right/left edge of the aorta and anterior downward to the lumboaortic nodes and the interaorticocaval space. Description of the pathways appears difficult in clinical practice and impossible to predict for a malignant adrenal tumor [7]. Regarding the anatomic descriptions and clinical reviews lymphadenectomy should be include, at least, periadrenal/perirenal fat and renal hilum [8]. Routinely dissection of paraaortic and/or paracaval lymph nodes ipsilateral to the tumor is still debated without preoperartive imaging showing node involvement [8].
In the work cited previously by Panjwani et al. [6], the authors studied the impact of lymph node involvement on the disease’s prognosis. As mentioned above, lymph node involvement significantly reduces overall survival: 19% of N+ patients were alive after five years compared to 63% of N- patients. In a multivariate analysis, lymph node involvement remained a predictive factor of mortality (relative risk: 2.06, p=0.0048). Another important piece of data in this study is the definition of the minimum number of lymph nodes that have to be resected to assure the lymph node status. This minimum number is four.
The first (retrospective) study that highlighted the impact of lymph node dissection in the initial treatment of a malignant adrenocortical carcinoma is the German study by Reibetanz et al. [9]. The authors used the data from the German Adrenocortical Carcinoma Registry. The operational and anatomo-pathological reports of 563 patients were analyzed. Only patients classed as ENSAT stages I, Il and III with RO resection and monitored for at least six months were included (283 patients). Lymph node dissection is defined as the surgeon’s choice to resect lymph nodes regardless of the number of lymph nodes on the area to be removed. A consensus among the authors has concluded that patients with fewer than five lymph nodes did not have a “real” dissection. The research by Panjwani et al. [6] showed a similar result (four lymph nodes). In total, 283 patients were included and 47 (16.6%) had lymph node dissection. The two groups of patients are differentiated by 1) the size of the tumors: median 10.0 cm (2.3-30.0) in the group without dissection compared to 12.0 (4.0-39.0) with dissection (p=0.007), 2) the rate of local invasion: 51.1% of ENSAT stage III with dissection compared to 27.1% without dissection (p=0.002), 3) the rate of extended resection: 46.8% with dissection compared to 17.8% without dissection (p<0.001). At the end of a median follow-up period of 59 months (8-273) for the dissection group and 39 months (6-326) for the non-dissection group, 68.1% of patients with dissection (32/47) had a recurrence, compared to 60.6% of non-dissection patients (143/236) (p=0.36). 86 patients died; 14 (28.9%) from the dissection group and 72 (30.5%) from the non-dissection group. The presence of lymph node metastases (25 patients with metastases compared to 258 without lymph node metastases) was a disadvantageous factor. The median recurrence period was shorter (12.5 months compared to 31.3, p=0.058), as was cause-specific survival (86.4 months compared to 135 months, p=0.002). The interesting result was that among N+ patients, those who had had lymph node dissection had a better median for recurrence-free survival (20.4 versus 9.9 months, p=0.086) and better cause-specific survival (>86 versus 26.2 months, p=0.06) than patients with invaded lymph nodes without real dissection. A multivariate analysis showed that the risk of recurrence (p=0.042) and the risk of death linked to the illness (p=0.049) were significantly improved by lymph node dissection.
These results were confirmed by a recent study by Gerry et al. [10]. This study evaluated the impact of dissection (defined as the surgeon’s choice to carry out this dissection, not by the number of lymph nodes resected) on survival. Among the 265 patients who had operations in the 13 centers in the USA, 120 were evaluated; 32 (27%) had an intention of dissection and 88 (73%) did not. The tumors of patients with dissection were larger (12 cm versus 10 cm, p=0.07) and more frequently had lymph nodes that were visible on the pre-surgery imaging (44% versus 7%, p<0.001). In a univariate analysis,
overall survival after five years was better for patients with dissection (76% vs. 59%, p=0.041). In a multivariate analysis, dissection remained independently associated with a lower risk of death (OR 0.17, p=0.006). Despite the retrospective nature of these studies, it can be clearly seen that lymph node dissection is necessary in treating a malignant adrenocortical carcinoma.
4. Is It Necessary to Resect Neighboring Organs?
Marincola-Smith et al. [11] evaluated the impact of resecting neighboring organs. The authors used the data from 13 centers in the USA from 1993-2014 (US-ACC Group). Out of 265 initial patients, 167 non-metastatic patients were included. They were divided into two groups according to whether the adrenalectomy was isolated or associated with resecting neighboring organs. Venous resections and tumor thrombectomies were not considered as being resections of neighboring organs. Among the 167 patients, 99 (59.3%) had an isolated adrenalectomy and 68 had an extended resection. There was no difference between ages, sex or ASA classification. 26 patients (38.2%) had several organs resected. The most frequently resected organs were the kidney (38, 55.9%), the liver (19, 27.9%), the spleen (16, 23.5%), and the pancreas (11, 16.2%). The patients in the adrenalectomy only group had smaller tumors (10 cm vs. 13 cm, p<0.001) and were less often N+ patients (p<0.001). Among the 68 patients with an extended resection, 52 (76.5%) were not affected beyond the adrenal area in the definitive histological exam. The RO resection rates were the same between the two groups (67.6% for only adrenalectomy and 66.7% for extended resections). The rates of R1 (22.1% and 21.2%, respectively) and R2 (macroscopically incomplete resection) (4.4% and 2.0%, respectively) resection were also the same. The rates of intraoperative ruptures were also the same (12.1% and 7.4%, respectively; p=0.4). There was no difference in the median overall survival (p=0.47), in cause-specific survival (p=0.442) or in survival without recurrence (0.299) between the two groups. The median survival rates were 91.8% after one year, 53.4% after five years and 37.0% after ten years in the isolated adrenalectomy group. The results were 83.3%, 52.4%, and 45.2%, respectively for patients with an extended resection. Among the patients who had a recurrence, the rates of local and distant recurrence were not statistically different between the two groups - local recurrences were 40% after isolated adrenalectomy and 22% after extended adrenalectomy; distant recurrences were 45% and 51%, respectively; local and distant recurrences were 15% and 26%, respectively, p=0.093. In a multivariate analysis, the resection of neighboring organs did not change survival. Furthermore, among T1-T3 patients with clean margins, the extended resection did not further improve survival (p=0.149). The authors concluded that in the absence of suspected or known extra-adrenal invasion, resecting the adjacent organs is, in principle, unnecessary.
In practice the resection of neighboring organs should can be considered without real local invasion but also or only because intraoperative tumor rupture must absolutely avoided.
5. Treating Recurring Adrenal Carcinomas
A recent study by Glenn et al. [12] evaluated the frequency and sites of recurrence after surgical treatment for adrenal carcinomas. This study focused on 354 patients who were treated between 1983 and 2017. 70% of patients had a recurrence (249 patients). The median period of survival without recurrence was 11 months (1-200). In order from earliest appearance, the sites were at the following: lungs, liver, other rare sites (brain, axial skeleton, abdominal wall), peritoneal cavity, and the tumor bed. The initial laparoscopy was a risk factor for peritoneal recurrence (31% vs. 16%, RR: 1.8, p=0.02). Patients who were treated with radiotherapy had fewer local recurrences (tumor bed) than those who did not receive radiotherapy treatment: 13% vs. 34%, RR: 0.4, p=0.001. Of the 242 patients who had recurrences, 142 did not undergo surgery again. The period before the recurrence appeared was 8 months. These patients more often had multiple pulmonary recurrences than those who were
operated on again. 100 patients were operated on again and for 80% of them, the surgery was intended to be curative. The median period before the recurrence appeared was 17 months (0.8-179). Among these patients, 79 presented a second recurrence in a median period of 6 months (0.2-191). 37 patients had a third procedure. In total, 29% of the total number of patients did not develop a recurrence over the course of their follow-up (median: 28 months, 0-180), 34% had one recurrence and the remaining group had at least two recurrences. Patients who had a maximum of three procedures seemed to have benefitted from surgery (in overall survival). It should be noted that it was probably the patients who were in a better general state that were able to have these repeated surgeries. No repeat actions were described as having been carried out by laparoscopy. The authors concluded that the tumor grade, the extra-adrenal extension, the areas of the first multiple recurrences and a period of less than 12 months before appearance were all negative factors for survival. Furthermore, the duration of overall survival was linked to the site of recurrences and so the list of sites is given from the most to least serious: multiple sites, peritoneal cavity, liver, lungs, other rare sites (cf.), and tumor bed.
A study from the German Malignant Adrenocortical Carcinoma Registry reported the results of treatment on 154 patients who had a recurrence [13]. In this study, the rate of recurrence was 62%. The median period was 11 months (1-224). The recurrence was local (tumor bed) for 27%, distant for 37% and at both localizations for 36%. The lungs and the liver were the most frequently affected sites. As in the preceding article, no laparoscopic surgery was described in this study of repeat surgeries. In a multivariate analysis, two factors were associated with overall survival after recurrence: the period of appearance with a cut-off at 12 months and the quality of the recurrence’s resection. The median survival without recurrence after the second surgery was 10 months if the recurrence appeared after 12 months and 4 months if it appeared in under 12 months (p=0.001). The median survival rate without recurrence was 19 months after a second RO surgery, 9 months after a second R1 surgery, and 6 months after a second R2 surgery.
A 2017 French study followed 59 patients who were treated for recurring adrenocortical carcinoma [14]. Among this number, 29 were operated on, all using laparotomy. Surgery for recurrence and a period of occurrence below 12 months were two factors that favored survival.
In view of some experiences of repeat surgery reported in the literature, it appears that laparoscopy was not used in this indication.
6. Recent Comparative Studies: Laparoscopy Versus Laparotomy
In 2010, the team at the Gustave Roussy Institute published a retrospective study of 64 patients. 18 (28%) presented peritoneal carcinomatosis afterwards and the only predictive factor was the initial approach: 67% of carcinomatosis after laparoscopy versus 27% after laparotomy (p=0.016). However, this retrospective study focused on patients who had operations in previous years and were monitored by the Gustave Roussy Institute between 2003 and 2009. This period corresponds to the beginning of the experience with laparoscopic surgery and the number of patients who initially had a laparoscopic operation was only six, translating to a learning curve from the start [15].
Several studies have shown the feasibility of laparoscopic surgery for adrenocortical carcinomas with equivalent results in terms of the quality of the excision (margins, lymph node dissection) and overall survival without recurrence compared to laparotomy. Nevertheless, and despite these results, the debate on the approach remains, and no consensus has been reached because although a surgical approach by laparoscopy has known advantages in terms of post-operative rehabilitation, the publication of some oncological results are more difficult to interpret, or express reservations.
In a recent 2018 study, Wu et al. studied [16] the results and follow-up of patients who underwent operations for stage I and II adrenocortical carcinomas. This was a retrospective monocentric study from 2009 to 2017. Survival and survival without recurrence were studied. The two groups (laparotomy n=23/laparoscopy n=21) were comparable. The period of hospitalization was significantly shorter (p=0.002) for the laparoscopy group (6 days +/-2) than for the laparotomy group (9 days +/-4). The oncological results for a period of observation and monitoring that was identical for the two groups showed an identical overall rate (p=0.989) of local, peritoneal and metastatic recurrences (52% in the two groups). The time of the recurrence’s appearance was not significantly different (p=0.564) at 22 months in the laparotomy group and 25 months in the laparoscopy group. On the other hand, there was a significant difference (p=0.035) in terms of local and peritoneal recurrences with 42% for the laparoscopy group versus 22% for the laparotomy group. Lastly, the overall survival and median survival without recurrence was not significantly different between the two groups (p=0.635 and p=0.802, respectively) at 43% versus 47% and 36% versus 39%, respectively. The authors concluded that although overall development in terms of survival and metastatic development are more due to the tumor’s biology, local and peritoneal recurrences are more directly impacted by the surgical techniques themselves and that therefore, the results of the study suggest that excision by laparotomy must remain the norm for a proven adrenocortical carcinoma or for an adrenal tumor that is strongly indicative of an adrenocortical carcinoma.
The overall results on survival and survival without recurrence in this study by Wu et al. [16] are generally in keeping with those published by Donatini et al. [17] and Brix et al. [18], which did not find any further differences with regard to survival and survival without recurrence. These results were supported by two studies from the German [19] and Italian [20] registries. In addition to others, these studies encouraged some surgical teams to operate on adrenocortical carcinomas by laparoscopy, but Wu et al.’s conclusions suggest not using the same laparoscopy on the higher rate of local and peritoneal recurrence [16].
Zheng et al. [21] came to the same conclusion in another study published in 2018. This was a retrospective study of 42 patients who underwent operations for stage I to III adrenocortical carcinomas; 20 operations were carried out by laparoscopy and 22 by laparotomy. The average size of the lesions was significantly (p=0.001) larger for those who had a laparotomy than for those who had a laparoscopy (10.1 cm +/- 3.6 cm versus 6.3 cm +/- 2.2 cm). The research aim was to study survival without recurrence after one, two and three years. This period was on average significantly (p=0.023) longer in the group of patients who were operated on by laparotomy (44.8 months +/- 35 versus 17.5 months +/- 10.4). It was not significant after one and three years but it was significant (p=0.036) after two years (61.1% versus 21.4%). The other result of this study was that 100% of patients in the laparoscopy group presented at least one local recurrence (alone or associated with other sites) when the progressive tumor recurrence was diagnosed compared to 61% in the laparotomy group (p=0.03). These figures for local recurrences were much higher than in the literature.
Calcatera et al. [22] used the National Cancer Data Base to study survival after five years and the conversion factors. 588 patients were operated on for an adrenocortical carcinoma, regardless of stage, from 2010 to 2014: 200 were by laparoscopy and 388 were by laparotomy. The tumors operated on by laparoscopy were smaller than those operated on by laparotomy (p<0.001) but the results on extended margins were identical (p=0.56). The conversion rate was 38/200 (19%). The average tumor size in the conversion group was 10.2 cm versus 8.6 cm in the full laparoscopic procedure group. Only sizes greater than 5 cm were found to be a predictive factor of conversion. Beyond these purely technical aspects, the aim of this study was to show that although the two laparoscopy (n=200)/laparotomy (n=388) groups were comparable in terms of survival (p=0.93), this was not the
same for the group of converted patients (n=38) compared to the group of patients who had a full laparoscopy procedure (n=162) with survival of 60% after one year versus 80% and no survivors after four years versus 50%. The statistical study shows that the larger tumor size in the converted group alone was not enough to explain this poor prognosis and that there must be other factors, without mentioning them. These results suggest that a laparoscopic surgery should be planned only if it is foreseeable to carry out the full resection using this method. Conversely, a laparotomy should be carried out straight away if a laparoscopy-laparotomy conversion is planned from the start of the procedure or is strongly foreseeable based on the size of the tumor. However, some authors in this review started some tumor surgeries strictly from an intra-adrenal approach by laparoscopy in order to remove the liver or spleen/pancreas. Then, in principle, a conversion is carried out by limiting the size of the laparotomy. In this way, there is no dissection of the tumor by laparoscopy.
In the sense indicated by this “foreseeable” conversion, it is possible to note the problem of acquiring the expertise (learning curve) to carry out this procedure: Guerrieri et al. [23] demonstrated that the operating time and, above all, the rate of conversion on a study of 241 adrenalectomies by laparoscopy were significantly impacted by the number of procedures carried out with a cut-off at 30 procedures on the right side and 40 for the left. Likewise, Bittner et al. [24] illustrated that the need for associated resections was a significant risk factor (p<0.01) of conversion to laparotomy. The individual experience of surgery and the concept of foreseeable associated actions are therefore likely to be the pre- operative decision-making factors that are more important in evaluating the choice of approach than other recognized factors like the size of the tumor, primarily.
It can be seen by reading recent literature that the “laparotomy versus laparoscopy” debate for surgically treating adrenocortical carcinomas is still topical. For some, laparotomy is still the gold standard in treatment in terms of results on survival, survival without recurrence, the type of recurrence (local or peritoneal), excision margins, etc. [15, 25-29]. A 2015 meta-analysis by Sgourakis et al. [30] found a significant difference in survival only after five years, in favor of laparotomy. In contrast, several studies - excluding the procedure’s technical feasibility and the intra-operative benefit that comes with laparoscopy - show that for surgeons said to be “experienced” (the definition of which remains imprecise) and for selected lesions, especially smaller ones (<5 cm?), the oncological results are identical to those obtained by laparotomy, particularly the absence of invaded neighboring organs [17-20]. The study by Brix et al. [18] of 152 patients was also representative of this.
7. Conclusions.
In order to draw conclusions, there must be a randomized prospective study comparing laparoscopy and laparotomy for adrenal tumors that are suspected of being adrenocortical carcinomas of less than 5-6 cm, with stratification on carrying out lymph node dissection, with an objective of studying the appearance time of local and/or distant recurrences.
Although a comparability between the two surgical techniques has been demonstrated for tumors of this size, another comparable study can also be planned for adrenal tumors suspected of being adrenocortical carcinomas measuring less than 10 cm.
Given the rarity of these tumors, this study would have to be multi-center and probably international (based on the ENSAT network, for example) [31]. [table 3]
For tumors of 10 cm or more, it seems to be prudent, for now, to continue with laparotomy surgeries in view of the risks of invasions into veins, lymph nodes and neighboring organs in order to ensure monobloc resection without rupturing the tumor (major risk factor of early local-regional recurrence).
The treatment must meet the rules of oncological treatment with an R0 resection that removes the neighboring organs only in the event of proven or strongly suspected invasion and carries out lymph node dissection. A highly trained surgeon could probably resect strictly intra-adrenal tumors of up to 10 cm in diameter via laparoscopy. On the other hand, the risk of conversion after “traumatic” dissection for the tumor risks exposing the patient to an early local recurrence and a lower survival rate. An immediate laparotomy for a 5-10 cm tumor that is suspected to be malignant is not a medical hazard.
Journal Pre-proof
References
[1] Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromcytoma. New Eng J Med 1992; 327: 1033.
[2] Vorselaars WM, Postma EL, Mirallie E, Thiery J, Lustgarten M, Pasternack JD, et al. Hemodynamic instability during surgery for pheochromocytoma: comparing the transperitoneal and retroperitoneal approach in a multicenter analysis of 341 patients. Surgery 2018; 163: 176-82.
[3] Greilsamer T, Nomine-Criqui C, Thy M, Ullmann T, Zarnegar R, Brelser L, et al. Robotic-assisted unilateral adrenalectomy : risk factors for perioperative complications in 303 consecutive patients. Surg Endosc 2018 DOI 10.1007/s00464-018-6342-2
[4] Economopoulos K, Mylonas K, Stamou A, Theocharidis V, Sergentanis T, Psaltopoulou T, et al. Laparoscopic versus robotic adrenalectomy : a comprhensive meta-analysis. Int J Surg 2017 ; 38 : 95- 104.
[5] Margonis GA, Kim Y, Prescott JD, Tran TB, Postlewait LM, Maithel SK, et al. Adrenocortical carcinoma : impact of surgical margin status on long-term outcomes. Ann Surg Oncol 2016; 23: 134- 41.
[6] Panjwani S, Moore MD, Gray KD, Finnerty BM, Beninato T, Brunaud L, et al. The impact of the nodal dissection on staging in adrenocortical carcinoma. Ann Surg Oncol 2017: 24; 3617-23.
[7] Gaujoux S, Brennan M. Recommendation for standardized surgical management of primary adrenocortical carcinoma. Surgery 2012; 152: 123-32.
[8] Gaujoux S, Weinandt M, Bonnet S, Reslinger V, Bertherat J, Dousset B. Surgical treatment of adrenocortical carcinoma. J Visc SURG 2017; 154: 335-43.
[9] Reibetanz J, Jurowich C, Erdogan I, Nies C, Rayez N, Dralle H, et al. Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. Ann Surg 2012; 255 : 363-69.
[10] Gerry JM, Tran TB, Postlewait LM, Maithel SK, Prescott JD, Wang TS, et al. Lymphadectomy for adrenocortical carcinoma: is there a therapeutic benefit? Ann Surg Oncol 2016: 23; 708-13.
[11] Marincola Smith P, Kiernan CM, Tran TB, Tran TB, Postlewait LM, Maithel SK, et al. Role of additional organ resection in adrenocortical carcinoma: analysis of 167 patients from the US adrenocortical database. Ann Surg Oncol 2018: 25; 2308-15.
[12] Glenn JA, Else T, Hughes DT, Cohen MS, Jolly S, Giordano TJ, et al. Longitudinal patterns of recurrence in patients with adrenocortical carcinoma. Surgery 2019: 165; 186-95.
[13] Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M, et al. The role of surgery in management of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab 2013; 98: 181-91.
[14] Simon G, Pattou F, Mirallie E, Lifante JC, Nomine C, Arnault V, et al. Surgery for recurrent adrenocortical carcinoma: a multicenter retrospective study. Surgery 2017: 161; 249-56.
[15] Leboulleux S, Deandreis D, Al Ghuzlan A, Aupérin A, Goéré D, Dromain C, et al. Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis ? Eur J Endocrinol 2010; 162: 1147-53.
[16] Wu K, Liu Z, Liang J, Tang Y, Zou, Z, Zhou C, et al. Laparoscopic versus open adrenalectomy for localized (stage I/II) adrenocortical carcinoma : experience at a single high-volume center. Surgery 2018; 164: 1325-29.
[17] Donatini G, Caiazzo R, Do Cao C, Aubert S, Zerrweck C, El-Kahib Z, et al. Long-term survival after adrenalectomy for stage I/II adrenocortical carcinoma (ACC): a retrospective comparative cohort study of laparoscopic versus open approach. Ann Surg Oncol 2014; 21: 284-91.
[18] Brix D, Allolio B, Fenske W, Agha A, Dralle H, Jurowich C, et al. laparoscopic versus open adrenalectomy for adrenocortical carcinoma : surgical and oncologic outcome in 152 patients. Eur Urol 2010; 58: 609-15.
[19] Porpiglia F, Fiori C, Daffara F, Zaggia B, Bolito E, Volante M, et al. Retrospective evaluation of outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer. Eur Urol 2010; 57: 873-78.
[20] Lombardi CP, Rafaelli M, De Crea C, Boniardi M, De Toma G, Marzano LA, et al. Open versus laparoscopic adrenalectomy in the treatment of localized (stage I/II) adrenocortical carcinoma: results of a multiinstitutional Italian survey. Surgery 2012; 152:1158-64.
[21] Zheng GY, Li HZ, Deng JH, Zhang XB, Wu XC. Open adrenalectomy versus laparoscopic adrenalectomy for adrenocortical carcinoma: a retrospective comparative study on short-term oncologic prognosis. Onco Targets Therapy 2018: 11 ; 1625-32
[22] Calcatera NA, Hsiung-Wang C, Suss NR, Winchester DJ, Moo-Young TA, Prinz RA. Minimally invasive adrenalectomy for adrenocortical carcinoma: five-years trends and predictors of conversion. World J Surg 2018; 42 : 473-81.
[23] Guerrieri M, Camapagnacci R, De Sanctis A, Baldarelli M, Coletta M, Peretta S. The learning curve in laparoscopic adrenalectomy. J Endocrinol Invest 2008; 31: 531-36.
E
[24] Bittner JG, Gershuni VM, Matthews BD Moley JF, Brunt LM. Risk factors affecting operative approach, conversion, and morbidity for adrenalectomy: a single-institution series of 402 patients. Surg Endosc 2013; 27: 2342-50.
[25] Miller BS, Gauger PG, Hammer GD, Doherty GM. Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy. Surgery 2012; 152: 1150-57.
[26] Ball NW, Hemal AK, Allaf ME. International consultation on urological diseases and European association of urolgy international consultation on minimally invasive surgery in urology: laparoscopic and robotic adrenalectomy. BJU Int 2017; 119: 13-21.
[27] Cooper AB, Habra Ma, Grubbs EG, Bednarski BK, Ying AK, Perrier ND, et al. Does laparoscopic adrenalectomy jeopardize oncologic outcomes for patients with adrenocortical carcinoma? Surg Endosc 2013; 27: 4026-32.
[28] Mir MC, Klink JC, Guilloteau J, Long JA, Miocinovic R, Kaouk JH, et al. Comparative outcomes of laparoscopic and open adrenalectomy for adrenocortical carcinoma: single high-volume center experience. Ann Surg Oncol 2013; 20: 1456-61.
[29] Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma. World J Surg 2010; 34: 1380-85.
[30] Sgourakis G, Lanitis S, Kouloura A, Zaphiriadou P, Karkoulias K, Raptis D, et al. Laparoscopic versus open adrenalectomy for stage I/II adrenocortical carcinoma: meta-analysis of outcomes. J Invest Surg 2015; 28:145-52.
[31] Gaujoux S, Mihai R. ESES and ENSAT recommendations for surgical management of adrenocortical carcinoma. Br J Surg 2017; 104: 358-76.
Journal Pre-proof
Key points
R0 surgical resection is the main recognized factor for a best free-disease and overall survivals.
Lymph nodes metastasis is a predictive factor of mortality in relationship with the tumor. The disease-free and overall survivals are best, even in the N+ group, if the patient have an elective lymphadectomy.
Without suspicion of regional invasion at preoperative imaging routine resection of neighboring organs seems not increase overall survival. This regional resection of organs is associated to a specific morbidity.
Complete local resection of recurrence is possible. Laparoscopic approach in this case is not recommended. Resection of hepatic or pulmonary metastasis is also possible if RO resection is predictive and if local disease is free. &
Laparoscopic approach versus open surgery is still debatted. Laparoscopic approach must be done in a surgical team with an expertise in adrenal surgery and with respect of oncologic procedures. With a suspected metastatic lymph nodes and/or adjacent local invasion at the preoperative imaging laparoscopic approach is not recommended. In suspected or proved malignant tumor of adrenal gland laparotomy is still “the gold standard” approach.
Journal Pre-pr