The results of our study reveal no disadvantages in employing the laparoscopic approach to large (≥6 cm) pheochromocytomas. In our series, there was no difference in intra- operative hypertension, length of stay, or post-operative complications. Patients who presented with larger tumors, had a similar immediate post-operative recovery as the SmPheo group. There were no incidents of capsular invasion, irrespective of size, and to date, there have been no recurrences or cancer diagnoses. Our patients also did not experience any adverse cardiovascular events (myocardial infarction or cerebrovascular accident). Minor liver and spleen tears were encountered in two patients.
The benefits of laparoscopic surgery are many including decreased length of stay, faster functional recovery, early ambulation, safety, decreased peri-operative morbidity, and similar rate of conversion and morbidity to other adrenal tumors, despite their average larger size (1
). These benefits refer to laparoscopic adrenalectomy for all adrenal pathologies, including pheochromocytomas. Some studies have cited an upper size limit of 12 cm to 14 cm for adrenal tumors that are resected laparoscopically (24
). However, due to the catecholamine surge and possible adverse peri-operative cardiovascular events, the upper limit for pheochromocytomas has traditionally been much smaller (5
). Using the 6 cm cutoff for performing laparoscopic adrenalectomy we would have deprived 42.3% of our patients the benefits of a minimally invasive approach. Similarly, a cutoff of 8 cm would deny 23% of our patients the same benefits.
Cardiovascular instability due to excessive catecholamine release caused by CO2
pneumoperitoneum and/or dissection, has always been a concern, irrespective of the surgical approach. In Gagner’s initial report, he cited 58% intra-operative hypertension (SBP > 200mmHg) and 53% hypotension (SBP <90mmHg) in 1996 (1
). Despite this being a new frontier in surgery, his results were favorable to those of the traditional open approach (26
). Our results show continued improvement compared with the literature. With the use of more stringent criteria for hypertension (SBP ≥180mmHg) only 8% experienced intra-operative hypertension and only 23% had hypotension. One patient in the LgPheo group did require intra-operative intravenous anti-hypertensive medication for his hypertension, and two patients (one in each group) required pharmacologic pressure support, in addition to volume resuscitation, for their hypotension. Only one patient in the LgPheo group required transfusion of blood products.
Cardiovascular instability is at the core of intra-operative complications in patients who present with pheochromocytomas, requiring continuous invasive monitoring by both anesthesia and surgical teams, with pharmacologic intervention when warranted, and minimal tumor manipulation. Several studies have shown that tumor manipulation is the most significant intra-operative stimulus for catecholamine release during both open and laparoscopic approaches (13
). This is where operative experience with larger pheochromocytomas can make a difference in outcome. Rocha et al. reported that even with early adrenal vein ligation, it is most likely the vascularity that results in the large amount of hormone release (13
). Even though we did not measure intra-operative catecholamine levels, our strategy of minimal direct manipulation of both the tumor and the adrenal gland and early venous control suggests that this surgical technique employed by experienced surgeons results in low incidence of catecholamine-induced cardiovascular instability.
It has been suggested that an increased pheochromocytoma size is associated with increased risk of malignancy. We believe that any sign of suspected malignancy on pre-operative imaging should result in open surgery. None of the laparoscopic adrenalectomies performed was for cancer, as the only one malignant pheochromocytoma was suspected pre-operatively and that patient underwent an open operation. In this case, the capsule was preserved, and there has been no evidence of recurrence. Despite undergoing the open procedure, this patient did not experience any significant morbidity or mortality. The benefits of performing an open adrenalectomy in the face of malignant pheochromocytoma include safer removal of the cancer, without risking malignant pheochromocytomatosis, and the ability to evaluate metastases.
Our study has a few limitations. First, it is a retrospective study on a prospective database. Due to the rare incidence of large pheochromocytomas it is unlikely that a prospective randomized trial will ever be conducted. The small number of patients in our study is comparable to other studies, some of which are multi-institutional and/or include other adrenal pathologies (1
). Despite the length of the study, where some patients have at least a five year follow-up, the rare occurrence of these tumors may require an even longer follow up. Our exclusion of patients with paragangliomas or open surgical resection resulted in selection bias and no known malignancy in our cohort. The aim of this study was to assess the role of laparoscopic surgery in large adrenal pheochromocytomas and the inclusion of paragangliomas and patients with initial open surgery was not appropriate to the study design. Lastly, the small number of patients in this study does not allow more than two subgroups and therefore our conclusions are limited to the 6 cm cutoff.
The extremely small incidence of pheochromocytomas also limited our ability to evaluate malignant pheochromocytomas. One patient presented with locally invasive tumor, which was identified on pre-operative imaging, and another presented with a recurrence of her initial pheochromocytoma from five years earlier. Both of these patients underwent open resection, due to the invasiveness of the tumors.