Partial hepatic resections for metastatic neuroendocrine tumors: perioperative outcomes.

STUDY OBJECTIVE: Partial hepatic resection reduces tumor burden in patients with metastatic neuroendocrine tumors, thereby improving quality and length of life. These procedures can be challenging as well as life-threatening. Our aim was to evaluate our patients' perioperative outcomes and propose a definition for an intraoperative carcinoid crisis relevant to this surgery, given its unique surgical considerations. DESIGN: Retrospective study. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENTS: One hundred sixty-nine patients undergoing partial hepatic resection for metastatic neuroendocrine tumors between 1997 and 2015 were identified retrospectively from a surgical database at Mayo Clinic Rochester. INTERVENTIONS: None. MEASUREMENTS: Intraoperative carcinoid crisis for patients undergoing hepatic resection of neuroendocrine tumors was defined. Patients' medical records were reviewed and data were abstracted describing patient and procedural characteristics and perioperative outcomes. MAIN RESULTS: There were no documented cases of carcinoid crisis (0.0%, 95% C.I. 0.0% to 2.2%). One patient developed clinical findings of an emerging carcinoid crisis, but was successfully treated with doses of octreotide and findings resolved in <10 min. Prophylactically 500 µg octreotide was given subcutaneously in 77% (130/169) of patients preoperatively. CONCLUSIONS: There were no documented cases of carcinoid crisis (0.0%, 95% C.I. 0.0% to 2.2%). Adverse events were infrequent.

Pharmacology of Octreotide: Clinical Implications for Anesthesiologists and Associated Risks.

Many patients presenting with a history of foregut, midgut neuroendocrine tumors (NETs) or carcinoid syndrome can experience life-threatening carcinoid crises during anesthesia or surgery. Clinicians should understand the pharmacology of octreotide and appreciate the use of continuous infusions of high-dose octreotide, which can minimize intraoperative carcinoid crises. We administer a prophylactic 500-µg bolus of octreotide intravenously (IV) and begin a continuous infusion of 500 µg/h for all NET patients. Advantages include low cost and excellent safety profile. High-dose octreotide for midgut and foregut NETs requires an appreciation of the pathophysiology involved in the disease, pharmacology, drug-drug interactions, and side effects.

Development of effective prophylaxis against intraoperative carcinoid crisis.

STUDY OBJECTIVE: The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. DESIGN: A retrospective study was approved by the institutional review boards at Ochsner Medical Center-Kenner and Louisiana State University Health Sciences Center. SETTING: Ochsner Medical Center-Kenner operating room and multispecialty NET clinic. PATIENTS: One hundred fifty consecutive patients who underwent a total of 179 cytoreductive surgeries for stage IV, small bowel NETs. INTERVENTIONS: All patients received a 500-µg/h infusion of octreotide acetate preoperatively, intraoperatively, and postoperatively. MEASUREMENTS: Anesthesia and surgical records were reviewed. Carcinoid crisis was defined as a systolic blood pressure of less than 80mm Hg for greater than 10minutes. Patients who experienced intraoperative hypertension or hypotension, profound tachycardia, or a "crisis" according to the operative note were also reviewed. MAIN RESULTS: One hundred sixty-nine (169/179; 94%) patients had normal anesthesia courses. The medical records of 10 patients were further investigated for a potential intraoperative crisis using the aforementioned criteria. Upon review, 6 patients were determined to have had a crisis. The final incidence of intraoperative crisis was 3.4% (6/179). CONCLUSIONS: A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis. We believe that the low cost and excellent safety profile of octreotide warrant the use of this therapy during extensive surgical procedures for midgut and foregut NETs.

Continuous infusion of octreotide combined with perioperative octreotide bolus does not prevent intraoperative carcinoid crisis.

BACKGROUND: Operations and anesthesia in carcinoid patients can provoke carcinoid crises, which can have serious sequelae, including death. Prophylactic octreotide is recommended to prevent crises. Recommended prophylaxis regimens vary from octreotide long-acting repeatable to preoperative bolus to continuous octreotide infusion; however, efficacy data are lacking. We have shown previously that crises correlated with major complications and that octreotide long-acting repeatable and preoperative bolus failed to prevent crises. This study examines the impact of continuous octreotide infusion. METHODS: A total of 127 patients (71% with liver metastases, 74% with carcinoid syndrome) who underwent 150 operations with continuous octreotide infusions were enrolled in this prospective case series. Our main outcome measures were the occurrence of intraoperative carcinoid crises and post-operative complications. RESULTS: Crises occurred at a rate of 30% as compared with 24% in our previous series, which examined the impact of preoperative octreotide bolus. Crises were significantly associated with the presence of hepatic metastases (P = .02) or history of carcinoid syndrome (P = .006), although neither was required for crises. Prompt vasopressor treatment shortened the mean duration of hypotension to 8.7 minutes, compared with 19 minutes in our prior series. Crises no longer correlated with major complications (P = .481) unless instability persisted for greater than 10 minutes (P = .011). CONCLUSION: Octreotide infusions do not prevent intraoperative crises. Patients without liver metastases or carcinoid syndrome can have intraoperative crises. Postoperative complications can be decreased by reducing the duration of crises. Further study is needed to determine how best to shorten hemodynamic instability during crises.

Somatostatin analogues do not prevent carcinoid crisis.

BACKGROUND: Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis. MATERIALS AND METHODS: PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013. RESULTS: Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/ surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15). CONCLUSIONS: SSTA was not helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.

Octreotide LAR and bolus octreotide are insufficient for preventing intraoperative complications in carcinoid patients.

BACKGROUND AND OBJECTIVES: Surgery in carcinoid patients can provoke a carcinoid crisis, which can have serious sequelae, including death. Octreotide prophylaxis is recommended to prevent carcinoid crisis, however there are few reports of outcomes and no large series examining its efficacy. We hypothesized that a 500 µg prophylactic octreotide dose is sufficient to prevent carcinoid crisis. METHODS: Records of carcinoid patients undergoing abdominal operations during years 2007-2011 were retrospectively reviewed. Octreotide use and intraoperative and postoperative outcomes were analyzed. RESULTS: Ninety-seven intraabdominal operations performed by a single surgeon were reviewed. Ninety percent of patients received preoperative prophylactic octreotide. Fifty-six percent received at least one additional intraoperative dose. Twenty-three patients (24%) experienced an intraoperative complication. Intraoperative complications correlated with presence of hepatic metastases but not presence of carcinoid syndrome. Postoperative complications occurred in 60% of patients with intraoperative complications versus 31% of those with none (P = 0.01). CONCLUSIONS: Significant intraoperative complications occur frequently in patients with hepatic metastases regardless of presence of carcinoid syndrome and despite octreotide LAR or single dose prophylactic octreotide. Occurrence of such events correlates strongly with postoperative complications. Randomized controlled trials are needed to determine whether the administration of prophylactic octreotide is beneficial.

Surgical management of liver metastases from gastrointestinal endocrine tumors.

Liver metastases from endocrine tumors can reduce 5-year survival from 90% to 40% and, in cases of functional gastrointestinal endocrine tumors, lead to a carcinoid syndrome. Complete resection of cancerous disease should be considered in all cases. Indeed, after hepatectomy, prolonged survival (41-86% at five years) can be achieved, with low rates of surgery-related mortality (0-6.7%). Extended liver resection is required in most cases. Percutaneous portal embolization increases the volumetric feasibility of resection, and sequential hepatectomy techniques enable a two-stage resection of both bilobar metastases and the primary tumor. For carcinoid syndrome that does not respond to medical therapy, incomplete resection of liver metastases, by reducing tumor volume, may be indicated to reduce symptoms and halt the progression of carcinoid heart disease. In cases of non-resectable liver metastases in selected patients, liver transplantation can lead to 5-year survival rates as high as 77%.

Atypical carcinoid of the larynx and potential complications of the carcinoid syndrome: a case report.

A 47-year-old man with a history of allergic rhinitis presented with a several-month history of nasal symptoms and gastroesophageal reflux disease. He also had clinical depression, for which he had been taking a selective serotonin reuptake inhibitor (SSRI). During evaluation, flexible laryngoscopy incidentally detected a left interarytenoid polyp. Biopsy identified the lesion as a moderately differentiated neuroendocrine carcinoma. In addition to conducting a metastatic workup, we determined that it was necessary to evaluate the functional status of the tumor prior to excision because the SSRI could precipitate a carcinoid syndrome. We discuss the characteristics and management of different neuroendocrine carcinomas of the larynx, and we review the potential complications of the carcinoid syndrome.

Perioperative use of octreotide in gastrointestinal surgery.

The evolution of gastrointestinal endocrinology has led to the design and application of analogs of gut peptides to treat disease. Octreotide, a long-acting analog of the inhibitory peptide somatostatin, has proven useful in the management of disorders such as carcinoid syndrome and secretory diarrhea due to VIPoma. More recent experience suggests a role for this peptide in the management of certain complications of gastrointestinal surgery. Prophylactic use of octreotide appears warranted in the prevention of carcinoid crisis in selected patients with carcinoid syndrome undergoing invasive procedures, and in the prevention of complications in selected patients undergoing pancreatic surgery. Evidence from placebo-controlled trials supports a role for octreotide in the management of dumping symptoms in severely affected patients, at least in the short term. Octreotide appears to serve a useful adjunctive role in controlling output from postoperative gastrointestinal fistulae and may hasten closure, particularly in pancreatic fistulae. Selected patients with ileostomy diarrhea and short bowel syndrome benefit from octreotide treatment, but the long-term value of the peptide in controlling stool output is less clear. Rare patients with other forms of postoperative secretory diarrhea have been successfully treated with octreotide. Finally, animal and early human experience suggests that octreotide may have a role as an adjunctive treatment of partial small bowel obstruction. In most of these conditions, the available data is sparse and further controlled trials are warranted.

[Liver transplantation in metastases of carcinoid tumor]. / Transplantation hépatique pour métastases d'une tumeur carcinoïde.

A 30-year-old woman underwent a liver transplantation for metastasis of a carcinoid tumor of the midgut previously resected. Operative manipulation of the liver resulted in arterial hypotension, tachycardia, high pulmonary arterial pressure, oedema of the face and peripheral cyanosis, although the patient was given somatostatin (Modustatine, Clin-Midy) (300 micrograms a hour) prior to the procedure. The improvement of the symptoms was obtained by the increase of somatostatin infusion rate to 750 micrograms a hour associated with dopamine (6 micrograms.kg-1.min-1) and fluid replacement. The diagnosis of carcinoid syndrome is discussed. This unusual observation stresses the difficulty in preventing and/or treating a carcinoid shock. If somatostatin seems to be the treatment of choice of such a syndrome, its role in that case was limited.