Recognition and management of phaeochromocytoma and paraganglioma

Phaeochromocytomas and paragangliomas (PPGL) are catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. These tumours may be identified incidentally, as part of a work-up for multiple endocrine neoplasia or following haemodynamic surges during unrelated procedures. Advances in perioperative management and improved management of intraoperative haemodynamic instability have significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection where possible is associated with improved outcomes. Anaesthetic management of PPGL cases represents a unique haemodynamic challenge both before and after tumour resection. In this article we describe the physiology of these tumours, their diagnosis, preoperative optimization methods, intraoperative anaesthetic management and management of postoperative complications.     

Recognition and management of phaeochromocytoma

Phaeochromocytomas and paragangliomas (PPGL) are catecholamine-secreting neuroendocrine tumours. These tumours may be identified incidentally, as part of a work-up for multiple endocrine neoplasia or following haemodynamic surges during unrelated procedures. Advances in preoperative management and improved management of intraoperative haemodynamic instability have significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection where possible is associated with improved outcomes. Anaesthetic management of PPGL cases represents a unique haemodynamic challenge both before, during and after tumour resection. In this article we describe the physiology of these tumours, their diagnosis, preoperative optimization methods, intraoperative anaesthetic management and management of postoperative complications.     

Recognition and management of phaeochromocytoma

Phaeochromocytomas are potentially lethal catecholamine secreting tumours. 90% occur in the adrenal glands (10% are bilateral) and 10% are extra adrenal. Clinical presentation depends on the pattern of catecholamine secretion. The symptoms are diverse, but the most common are headache, diaphoresis and palpitations. These tumours are important to the anaesthetist because they can present unexpectedly perioperatively and the mortality is up to 50%. Diagnosis relies on the demonstration of excessive catecholamine production by 24 hour urine measurement. The tumour is usually localized by CT or MRI imaging. Excision of the tumour can only be undertaken safely when pharmacological control of the sympathetic nervous system and normovolaemia have been achieved. A number of antihypertensive agents have been used successfully in the perioperative period to maintain cardiovascular stability. Preoperative preparation should also include an assessment of myocardial function to exclude the presence of phaeochromocytoma associated cardiomyopathy. Adrenalectomy can be performed using an open or laparoscopic approach, with each procedure having implications for the anaesthetist. Management of intraoperative hypertensive surges and arrhythmias requires an understanding of the physiology and pharmacology of phaeochromocytomas. This article details the clinical presentation, diagnosis and perioperative anaesthetic management of elective and emergency phaeochromocytomas.     

PS10PHAEOCHROMOCYTOMA IN CHILDREN

Purpose Phaeochromocytomas are rare tumours of the sympathoadrenal neuroendocrine system. It is known that these tumours are associated with Von Hippel Lindau (VHL) disease, multiple endocrine neoplasia type II and neurofibromatosis type I. Recently an association with succinate dehydrogenase type B and D gene mutations has been described. Discovery of a SDHB mutation in a girl at our hospital prompted us to review our experience with phaeochromocytoma in children. Methodology Retrospective review of case notes of all children treated for phaeochromocytoma over the period 1997–2006 at Starship Children’s Hospital, NZ. Results Seven patients with 8 tumours were identified with average age of 10 years and average systolic BP of 161. The tumours were adrenal in location in 37.5% and 62.5% extra‐adrenal. Our malignancy rate was 12.5%. Familial disease was noted in two patients with one girl having VHL disease and the other found to carry a mutation in the SDHB gene. All children received preop antihypertensives and were treated operatively with seven open resections and one laparoscopic converted to open resection. One child received adjuvant radiotherapy. There were no recurrences or deaths. Conclusions Phaeochromocytoma in children varies from the adult form. It is more likely to be extra‐adrenal and have a greater chance of a familial genetic syndrome. The discovery of SDH mutations has altered the diagnosis of familial disease and carries implications for family screening, prognosis and surveillance. We emphasize the importance of taking a good family history and suggest screening for SDH mutations in all patients with phaeochromocytoma.     

Reoperative adrenal surgery: lessons learnt

With the widespread use of abdominal imaging, the detection and therefore incidence of adrenal tumours is increasing. The laparoscopic approach to primary surgical resection of adrenal tumours has now become the standard of care. There is scarce published literature regarding the management and outcomes of recurrent adrenal tumours. The aim of the present study was therefore to review the authors' experience with reoperative adrenal surgery. A retrospective review of reoperative adrenalectomy cases identified from the prospectively maintained University of Sydney Endocrine Surgical Unit Database from January 1988 to July 2007 was carried out. There were nine (3.5%) reoperative adrenalectomies in six patients. Two were cases of adrenocortical carcinoma, two involved cases of familial phaeochromocytomas and two cases were due to sporadic phaeochromocytomas. Reoperative adrenal surgery is an uncommon event. During the index surgery for adrenal tumours, all adrenal tissue should be removed and knowledge of the vagaries of adrenal anatomy is essential. Reoperative adrenal surgery is a safe procedure and may confer survival benefit or symptom relief. Lifelong follow up is essential for all patients who have had surgery for functional and malignant adrenal tumours.     

THE AETIOLOGY AND MANAGEMENT OF HEPATIC METASTASES

Hepatic metastases are a common event in the metastatic spread of primary tumours and indicate advanced disease. However, the presence of hepatic metastases does not necessarily imply incurability; in selected patients resection of hepatic metastases may result in 5-year survival rates of 25–35%, usually in patients with colorectal liver metastases in whom solitary metastases are more frequent than with other primary tumours. However, hepatic metastases from Wilm's tumours, adrenal tumours, renal cell carcinoma, and neuroendocrine tumours may also be resected with similar success rates. A poor prognosis after resection of hepatic metastases is likely when there are more than three metastatic deposits, involved resection margins (often as a result of ‘wedge’ resections), when there is extrahepatic disease, or nodal involvement at the primary tumour site. Cyto-reductive procedures may provide excellent palliation and possibly long-term survival in selected patients with hepatic metastases unsuitable for resection. However, further study is required to establish the appropriate role for these treatments.     

Recognition and management of phaeochromocytoma

Phaeochromocytomas are potentially lethal catecholamine secreting tumours. Clinical presentation depends on the pattern of catecholamine secretion. The symptoms are diverse, but the most common are headache, diaphoresis and palpitations. These tumours represent a challenge to the anaesthetist because they can present unexpectedly perioperatively and the mortality is up to 50%. Diagnosis relies on the demonstration of excessive catecholamine production by 24-hour urine measurement. The tumour is usually localized by CT or MRI imaging. Excision of the tumour can be undertaken safely only when pharmacological control of the sympathetic nervous system and normovolaemia have been achieved. A number of antihypertensive agents have been used successfully in the perioperative period to maintain cardiovascular stability. Preoperative preparation should also include an assessment of myocardial function to exclude the presence of phaeochromocytoma-associated cardiomyopathy. Adrenalectomy can be performed using an open or laparoscopic approach, with each procedure having implications for the anaesthetist. Management of intraoperative hypertensive surges and arrhythmias requires an understanding of the physiology and pharmacology of phaeochromocytomas. This article details the clinical presentation, diagnosis and perioperative anaesthetic management of elective and emergency phaeochromocytomas.     

The role of laparoscopic adrenalectomy for adrenal tumours of 6 cm or greater

Background Laparoscopic adrenalectomy (LA) has been shown to reduce hospital stay and morbidity when compared to open adrenalectomy (OA). It is uncertain if the laparoscopic resection of large (≥6 cm) potentially malignant adrenal tumours is appropriate due to concern over incomplete resection and local recurrence. The aim of the present study was to compare the outcomes of LA for tumours ≥6 cm with those < 6 cm. Methods Details of all patients referred with adrenal tumours between January 1999 and January 2006 had been recorded prospectively on a database. LA was performed using a lateral transabdominal approach. Contraindications to LA were local invasion requiring en bloc resection of adjacent organs or the requirement of additional open procedures. Results 103 patients were referred for adrenal resection. Three with metastatic adrenal carcinoma and two with severe cardiorespiratory disease were deemed unsuitable for operation. One hundred and eleven adrenalectomies were performed: 101 LAs and 10 OAs. Thirty-nine LA were for tumours ≥6 cm while nine OA were for tumours ≥6 cm. There were no significant differences between the median total anaesthetic time, postoperative complications or postoperative stay for patients undergoing LA for tumours ≥6 cm versus tumours <6 cm. Of the six conversions, five were performed for adrenal tumours ≥6 cm [local invasion (n = 3), adhesions (n = 1), primary renal carcinoma (n = 1)]. All tumours in the LA group were resected with clear margins and at a median follow up of 50 months (range 38–74 months). There has been no evidence of local recurrence. Conclusions In the absence of local invasion, the outcomes of laparoscopic adrenalectomy for patients with tumours ≥6 cm were comparable to those with tumours <6 cm. This has helped confirm a policy of initial laparoscopic resection for all noninvasive adrenal tumours can be applied safely.     

Bilateral adrenal lymphoma with Addison's disease : a surgical pitfall

A 65 year old man presenting with abdominal and back pain was found to have bilateral adrenal masses. Phaeochromocytomas were initially suspected on the basis of increased catecholamine excretion. This diagnosis seemed unlikely in view of clinical findings and a negative 123I-metaiodobenzylguanidine scintigraphy. A biopsy of the right adrenal mass revealed a diagnosis of primary adrenal B-cell lymphoma. Hyponatraemia and subtle clinical signs of adrenal insufficiency led to a diagnosis of Addison's disease, a common complication of primary adrenal lymphoma. Thus, bilateral adrenal masses associated with Addison's disease should raise the suspicion of possible primary adrenal lymphoma.     

Abdominal and pelvic tumours in children

While all childhood cancers are rare, the abdomen and pelvis are common sites of origin. After haematological malignancies and intracranial tumours, neuroblastoma is the most common childhood cancer, most often arising in the adrenal gland. The next most common extracranial tumours are Wilms tumour, arising in the kidney (nephroblastoma) and rhabdomyosarcoma that may arise in a variety of sites, typically in the pelvis. Hepatoblastoma, non-Hodgkin lymphoma and germ cell tumours are other abdominal and pelvic tumours seen in childhood. Many childhood tumours appear to arise from residual embryonic cells which make them sensitive to chemotherapy and radiotherapy. Surgery plays a crucial role both in establishing the diagnosis and, in the majority of cases, by resection of the tumour.     

Abdominal and pelvic tumours in children

While all childhood cancers are rare, the abdomen and pelvis are common sites of origin. After haematological malignancies and intracranial tumours, neuroblastoma is the most common childhood cancer, most often arising in the adrenal gland. The next most common extracranial tumours are Wilms tumour, arising in the kidney (nephroblastoma) and rhabdomyosarcoma that may arise in a variety of sites, typically in the pelvis. Hepatoblastoma, non-Hodgkin lymphoma and germ cell tumours are other abdominal and pelvic tumours seen in childhood. Many childhood tumours appear to arise from residual embryonic cells which make them sensitive to chemotherapy and radiotherapy. Surgery plays a crucial role both in establishing the diagnosis and, in the majority of cases, by resection of the tumour.     

Outcomes of minimally invasive surgery for phaeochromocytoma

Laparoscopic adrenalectomy is now accepted as the procedure of choice for the resection of benign adrenocortical tumours, but few studies have assessed whether the outcomes of laparoscopic adrenalectomy for adrenal phaeochromocytoma are similar to that of other adrenal tumour types. This is a retrospective cohort study. Clinical and operative data were obtained from an adrenal tumour database and hospital records. A total of 191 patients had laparoscopic adrenalectomy, of which 36 were for phaeochromocytoma, over a 12‐year period. Length of hospital stay (4.8 vs 3.6 days, P= 0.03) and total operating times (183 vs 157 min, P= 0.01) were greater in the laparoscopic phaeochromocytoma resection group. Despite the greater size of the phaeochromocytomas compared to the remaining adrenal tumour types (44 mm vs 30 mm, P < 0.01), however, rate of conversion and morbidity were no different. Laparoscopic adrenalectomy for phaeochromocytoma is a safe procedure with similar outcomes to laparoscopic adrenalectomy for other adrenal tumour types.     

Liver resection for neoplasm

Major hepatic resections can now be performed with much greater safety than formerly. This is largely a consequence of improved surgical and anesthetic techniques, which have in turn resulted from better understanding of the anatomy, physiology and biochemistry of the liver. The treatment of liver tumours by resection must be reappraised in the light of these advances. This paper reports twelve patients who have undergone major hepatic resection for neoplasm at the Royal Prince Alfred Hospital over a ten-year period. The current indications for such surgery in the treatment of benign and malignant liver tumours are reviewed, and the results discussed.     

LIVER RESECTION FOR NEOPLASM

Major hepatic resections can now be performed with much greater safety than formerly. This is largely a consequence of improved surgical and anaesthetic techniques, which have in turn resulted from better understanding of the anatomy, physiology and biochemistry of the liver. The treatment of liver tumours by resection must be reappraised in the light of these advances. This paper reports twelve patients who have undergone major hepatic resection for neoplasm at the Royal Prince Alfred Hospital over a ten-year period. The current indications for such surgery in the treatment of benign and malignant liver tumours are reviewed, and the results discussed.     

Abordaje laparoscópico en el tratamiento de las tumoraciones adrenales malignas

BackgroundMalignant primary or secondary adrenal tumours are uncommon. For most of them early surgery with adrenalectomy is the only means of cure. Although controversy exists on this issue, the increasing experience in laparoscopic surgery extends the indication for laparoscopic adrenalectomy to potentially malignant and to metastatic adrenal tumours. Our aim was to evaluate the technical feasibility of laparoscopic adrenalectomy for malignant neoplasias, describing the results of our consecutive series of patients.Material and methodsWe retrospectively analysed 13 patients who underwent laparoscopic adrenalectomy for malignant neoplasia between March 1999 and June 2009, at the Hospital de Clínicas of the Universidad of Buenos Aires and at the Hospital Alemán of Buenos Aires. A transperitoneal laparoscopic approach was used in all patients. The mean follow up was 37.9 months (2–84).ResultsThirteen laparoscopic adrenalectomies were performed due to malignant neoplasia. Mean age was 55.2+12 years. The relationship between male and female was 10/3. Five patients had an adrenal carcinoma, 1 patient a malignant phaeochromocytoma, and 7 patients had metastatic tumours. Three patients required conversion to laparotomy. Average operation time was 146.4 min. There were two perioperative complications and no mortality. Average length of hospital stay was 4.6 days (1–35). The survival at 3 years was 46%. The cause of death was the underlying disease in all cases.ConclusionLaparoscopic adrenalectomy is a reasonable technique for malignant adrenal tumours, when the open oncological resection can be reproduced by the laparoscopic approach.     

TNM-oriented therapy planning in bladder cancer

The standard diagnostic procedures for bladder carcinoma include transurethral resection, bimanual palpation of the bladder under general anaesthesia, ultrasound examination and CT scan of the abdominal and pelvic regions. An IVP is additionally carried out for the detection of concomitant upper urinary tract tumours. Preoperative urinary cytology is also performed, as in 10% of all patients the degree of malignancy of bladder cancer according to the TNM system is revealed more exactly by cytology than by histology. New computerized examination techniques have been designed in attempts to improve the accuracy of the diagnostic process. Therapeutic modalities according to the classification of bladder carcinoma in the TNM system have to be based on the different efficacies of the diagnostic procedure: In superficial low-grade tumours the diagnostic efficacy is quite high, so that transurethral resection remains the treatment of choice. Superficial high-grade tumours are attended by reduced 5-year survival rates, and patients with such tumours must therefore be regarded as a high-risk group. In muscle-invasive bladder carcinoma reduced diagnostic efficacy and unsatisfactory treatment results are seen, so that in this condition cystectomy at an early stage is indicated.     

From needles to numbers: can noninvasive imaging distinguish benign and malignant adrenal lesions?

Adrenal masses are a relatively common finding on computed tomography (CT) and magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or clinical follow-up were the only methods of distinguishing benign adenomas from malignancies. On the basis of their higher lipid content, adenomas have characteristic appearances on CT and MRI that can be used to separate them from non-lipid-containing lesions such as metastases. CT densitometry with or without contrast media and chemical shift MRI (CSI) are two examples of techniques with adequate sensitivity (50–90%) and excellent specificity (>95%) for adrenal adenomas. While the need for invasive tissue sampling is reduced because of these techniques, it is eliminated because lesions not meeting the criteria for adenomas are not always malignant. However, CT densitometry and CSI are likely to reduce significantly the need for histology sampling of incidentally discovered adrenal masses due to the high specificity of these new techniques.     

Influence of tumour differentiation on survival after resection for rectal cancer in a series of 1296 patients

The influence of differentiation grade on tumour staging, local recurrence and long term survival prospects has been evaluated in a series of patients managed by resection for rectal cancer. Differentiation was known in 1095 of 1296 patients. Well-differentiated tumours were over-represented among Dukes' stage A cases and poorly differentiated among those with disseminated disease (P less than 0.001). Local recurrence was twice as common (31%) after curative resection of poorly differentiated tumours than of well (14%) or moderately (17%) differentiated. Five year cancer specific survival rates after resection (curative and palliative combined) of tumours of good, average or poor differentiation were 68%, 59% and 33%, respectively. After potentially curative resection, survival was also significantly worse in patients with poorly differentiated tumours (P less than 0.001); 5 year survival rates of patients with tumours of good, average or poor differentiation were 75%, 71% and 51%, respectively. Survival prospects beyond 5 years in patients with Dukes' stage A tumours were significantly reduced when the tumour was poorly differentiated; 5 and 10 year survival rates were 76% and 40%, respectively. However, patients with Dukes' stage C tumours of poor differentiation had an identical 5 and 10 year cancer specific survival, 26%. Patients with mucoid type tumours had worse survival prospects than those with non-mucoid type (P less than 0.02).     

International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy

The aim of this study was to provide an evidence‐based systematic review of the use of laparoscopic and robotic adrenalectomy in the treatment of adrenal disease as part of the International Consultation on Urological Diseases and European Association of Urology consultation on Minimally Invasive Surgery in Urology. A systematic literature search (January 2004 to January 2014) was conducted to identify comparative studies assessing the safety and efficacy of minimally invasive adrenal surgery. Subtopics including the role of minimally invasive surgery for pheochromocytoma, adrenocortical carcinoma (ACC) and large adrenal tumours were examined. Additionally, the role of transperitoneal and retroperitoneal approaches, as well as laparoendoscopic single‐site (LESS) and robotic adrenalectomy were reviewed. The major findings are presented in an evidence‐based fashion. Large retrospective and prospective data were analysed and a set of recommendations provided by the committee was produced. Laparoscopic surgery should be considered the first‐line therapy for benign adrenal masses requiring surgical resection and for patients with pheochromocytoma. While a laparoscopic approach may be feasible for selected cases of ACC without adjacent organ involvement, an open surgical approach remains the ‘gold standard’. Large adrenal tumours without preoperative or intra‐operative suspicion of ACC may be safely resected via a laparoscopic approach. Both transperitoneal and retroperitoneal approaches to laparoscopic adrenalectomy are safe. The approach should be chosen based on surgeon training and experience. LESS and robotic adrenalectomy should be considered as alternatives to laparoscopic adrenalectomy but require further study.     

The value of a second transurethral resection in evaluating patients with bladder tumours

OBJECTIVES: To evaluate the usefulness of a second transurethral resection for superficial and muscle-invasive bladder tumours. METHODS: A review of the literature relevant to repeat resection for bladder tumours was conducted using Medline Services. RESULTS: Transurethral resection of the bladder has two shortcomings: underestimating clinical stage, and overlooking other lesions. A second transurethral resection, when performed 2-6 weeks after the initial resection, corrects clinical staging errors in 9-49% of cases and detects residual tumour in 26-83% of cases. A second resection is particularly warranted for T1 tumours since 2-28% of them prove to be muscle-invasive, thus requiring a change in management. For muscle-invasive tumours, a second resection may be performed only if bladder sparing is being considered, as it helps to exclude the presence of tumour sites contra-indicating conservative treatment. CONCLUSIONS: A second transurethral bladder resection may be warranted for T1 tumours, and for invasive tumours when a bladder preservation is planned.