Crisis carcinoide como una causa poco frecuente de choque distributivo / Carcinoid crisis as a rare cause of distributive shock

Los tumores neuroendocrinos son neoplasias que suelen tener un comportamiento clínico maligno, son provenientes de células entero cromafines y/o células productoras de gastrina. Según su origen anatómico, se clasifican en tumores del intestino anterior (comprometen estómago, duodeno, pulmones y páncreas), intestino medio (parte distal del duodeno) e intestino posterior (colon transverso hasta el recto). El síndrome carcinoide, presente en la mitad de los casos al momento del diagnóstico, se caracteriza por desencadenar episodios de diarrea, taquicardia, hipotensión, rubor (por el desarrollo de telangiectasias), y según la gravedad, valvulopatías cardiacas. Por otro lado, la crisis carcinoide, una complicación infrecuente, está relacionada con episodios de choque, que cuando ocurren son consecuencia de la liberación en la circulación sistémica de aminas vasoactivas, posterior a un evento desencadenante. A continuación, se presenta el caso de un paciente masculino con antecedente de un tumor neuroendocrino de intestino delgado, quien luego de ser llevado a embolización de metástasis hepáticas, presentó una crisis carcinoide, y finalmente un choque distributivo refractario a tratamientos convencionales, incluyendo octreotide y vasopresores, que culminó con la muerte del paciente. Se realiza la discusión del caso clínico y la presentación de la literatura disponible, donde se describe la epidemiología, patogénesis, diagnóstico, clínica y tratamiento de esta entidad

Neuroendocrine tumors are neoplasms that usually have a malignant clinical behavior. They arise from enterochromaffin-like and/or gastrin-producing cells. According to their anatomical location they can be classified as foregut tumors (af- fecting stomach, duodenum, lungs and pancreas), midgut tumors (affecting distal portion of the duodenum) and hindgut tumors (affecting transverse colon to rectum). Carcinoid syndrome, occurring in half of the cases at the time of diagnosis, is characterized by episodes of diarrhea, tachycardia, hypotension, flushing (due to telangiectasia), and heart valve disease depending on their severity. On the other hand, the carcinoid crisis, a rare complication that is related to episodes of shock, occur as a consequence of the release of vasoactive amines into the systemic circulation after a triggering event. Here we describe a case of a male patient with a history of neuroendocrine neoplasm, who after embolization of hepatic metastatic lesions presented a carcinoid crisis, ending with a vasodilatory shock, refractory to conventional treatment including octreotide and vasopressors, which resulted in the death of the patient. A discussion of the clinical report and a review of the available literature are presented, including the epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment of this entity

Diabetes Insipidus Induced by Combination of Short-acting Octreotide and Lanreotide for Recurrent Carcinoid Crisis of Neuroendocrine Tumour: A Case Report.

Somatostatin analogue is useful in carcinoid crisis for symptom control. Optimal dosing of somatostatin analogues for carcinoid symptoms is not known. This case highlighted management issues using combination short-acting octreotide infusion with long-acting lanreotide during carcinoid crisis. The patient had left lung neuroendocrine tumour that metastasized to his liver and bone, post left lobectomy. Due to extensive metastasis to the liver causing recurrent carcinoid crisis, he required shorter interval long-acting lanreotide with continuous infusion of short-acting octreotide, which led to transient diabetes insipidus. Symptoms resolved with discontinuation of treatment. Somatostatin analogues, especially in combination, may inhibit the posterior pituitary resulting in diabetes insipidus. Prompt withdrawal of short-acting somatostatin analogue and initiation of desmopressin can reverse the complication. It is important to recognize this complication with combination of octreotide and lanreotide injections to avoid serious complications.

Tumores Neuroendocrinos: un desafío transversal / Update on neuroendocrine tumors

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome.

BACKGROUND: Telotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods. METHODS: First occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial. RESULTS: In TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3-4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2-3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6-11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7-11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR. CONCLUSION: The time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01677910, NCT02063659.

Antiproliferative Effect of Above-Label Doses of Somatostatin Analogs for the Management of Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Above-label doses of somatostatin analogs (SSAs) are increasingly utilized in the management of inoperable/metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), progressing on standard 4-weekly regimens. OBJECTIVE: To evaluate the antiproliferative effect of 3-weekly SSA administration in a retrospective GEP-NET cohort. METHODS: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg at a 3-weekly interval, after disease progression on standard 4-weekly doses, were retrospectively identified. Clinicopathologic and treatment response data were collected. Progression-free survival (PFS; dose escalation to radiographic progression or death) was estimated with the Kaplan-Meier method. Factors associated with PFS were identified with the Cox proportional-hazards model. RESULTS: The inclusion criteria were fulfilled by 105 patients. Octreotide LAR was administered to 60 (57%) and lanreotide Autogel to 45 (43%). Indications for dose escalation were breakthrough carcinoid symptoms (58%), radiographic progression (35%) and/or increasing biomarkers (11%). Diarrheal and/or flushing symptomatic improvement was identified in 37/67 cases (55%) and 30/55 cases (55%) with available data, respectively. The disease control rate (radiographic partial response or stable disease) was achieved in 53 patients (50%). Median PFS was 25.0 months (95% CI 16.9-33.1). Patients with radiographic progression <12 months from 4-weekly SSA initiation had worse PFS after dose escalation (7.0 vs. 17.0 months, p = 0.002). In multivariate analysis, pancreatic NETs, a Ki-67 index ≥5% and multiple extrahepatic metastases were independently associated with inferior PFS. CONCLUSIONS: Above-label doses of SSAs may offer a considerable prolongation of PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, a Ki-67 index <5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.

Compromiso cardiovascular secundario a tumor carcinoide metastásico / Cardiovascular compromise secondary to metastatic carcinoid tumor

Resumen Los tumores carcinoides son neoplasias pertenecientes a la familia de tumores neuroendocrinos y presentan baja incidencia en la población en general; sin embargo, hasta el 50 % pueden debutar con compromiso cardiovascular. Se presenta el caso de un paciente, sin antecedentes cardiovasculares quien presentó signos y síntomas sugestivos de falla cardiaca derecha. Se le realizó ecocardiografía transtorácica que evidenció compromiso de ambas válvulas cardíacas derechas por tumor neuroendocrino metastásico, llevando al diagnóstico de sindrome carcinoide. Con el fin de tener presente dicha entidad en la práctica diaria de la cardiología clínica se revisan datos claves de abordaje diagnóstico y terapéutico.

Abstract Carcinoid tumors are neoplasms belonging to the neuroendocrine tumor family and have a low incidence in the general population; however, up to 50% may debut with cardiovascular involvement. We present the case of a patient, without a cardiovascular history, who presented signs and symptoms suggestive of right-sided heart failure. A transthoracic echocardiography was performed, which evidenced the involvement of both right heart valves by a metastatic neuroendocrine tumor, leading to the diagnosis of carcinoid syndrome. In order to take this entity into account in the daily practice of clinical cardiology, key data of diagnostic and therapeutic approach are reviewed.

Antiproliferative Effects of Telotristat Ethyl in Patients with Neuroendocrine Tumors: The TELEACE Real-World Chart Review Study.

PURPOSE: Neuroendocrine tumors (NETs) associated with carcinoid syndrome (CS) overproduce serotonin, mediated by tryptophan hydroxylase-1 (TPH1). The TPH inhibitor telotristat ethyl (TE) reduces peripheral serotonin and relieves CS symptoms. We conducted a real-world clinical practice study to explore the effects of TE on tumor growth in patients with NETs and CS. PATIENTS AND METHODS: Single-arm, pre/post chart review study of patients with advanced NETs who received TE for ≥6 months and had ≥2 radiological scans within 12 months before and ≥1 scan after TE initiation. Linear regression and longitudinal analyses assessed changes in tumor size controlling for background NET treatment. RESULTS: Two hundred patients were enrolled, most (61%) had well-differentiated gastrointestinal NETs (61%) and received TE for an average of 12 months (SD, 7.3). Mean reduction in tumor size after TE initiation was 0.59 cm (p=0.006). Longitudinal analysis showed an 8.5% reduction in tumor size (p=0.045) from pre- to post-TE periods. Documented NET treatment prior to initiating TE and time between scans were not significant predictors of changes in tumor size. Results were consistent in a subgroup of patients with the same documented NET treatment before and after initiating TE. CONCLUSION: TE may have antitumor effects consistent with serotonin overproduction in tumor growth.

Flushing as atypical initial presentation of functional gallbladder neuroendocrine carcinoma: A case report.

BACKGROUND: Neuroendocrine neoplasms are rarely located in the gallbladder (GB), and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms. CASE SUMMARY: We report a case of GB neuroendocrine carcinoma (GB-NEC) in a 65-year-old man, who presented with flushing for 2 mo. Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis. Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space. High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space, but distant metastasis was not seen by positron emission tomography. Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC. Because of the functional characteristics of poorly differentiated NEC, en bloc cholecystectomy, resection of hepatic segments IVb and V, pancreaticoduodenectomy, and regional lymphadenectomy were performed. A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data. Ki-67 index was > 80%. The patient refused adjuvant therapy and passed away in the 7th month. CONCLUSION: Distinctive manifestation combined with imaging helps make correct preoperative diagnosis. Radical surgery and adjuvant chemotherapy might improve prognosis.

Must antidepressants be avoided in patients with neuroendocrine tumors? Results of a systematic review.

OBJECTIVE: Symptoms of depression and anxiety are common in neuroendocrine tumor (NET), yet controversy exists over whether serotonin-mediated antidepressants (SAs) are safe in this population. We sought to address this knowledge gap. METHOD: Following PRISMA guidelines, we conducted a systematic review to identify NET patients who were prescribed SA. RESULTS: We identified 15 articles, reporting on 161 unique patients, 72 with carcinoid syndrome (CS) and 89 without. There was substantial agreement between reviewers at the full-text stage (κ = 0.69). Three of the articles, all with low risk of bias, accounted for most of the cases (149/161; 93%). Among the 72 NET patients with CS prior to antidepressant usage, CS was exacerbated in 6 cases (8%), only 3 (4%) of whom chose to discontinue the antidepressant. The remaining 89 patients had no prior CS symptoms, and none developed CS following antidepressant usage. Overall, no instances of carcinoid crisis or death were reported. CONCLUSIONS: We found no evidence for serious adverse outcomes related to SA usage in NET patients. Previous authors have recommended avoiding antidepressants in NET, but our findings do not support those recommendations. Oncologists should nonetheless monitor for symptom exacerbation when prescribing SA to patients with NET.

Burden of Carcinoid Heart Disease in Patients With Carcinoid Syndrome Initiating Somatostatin Analogues.

PURPOSE: As a result of overproduction of serotonin, patients with uncontrolled carcinoid syndrome (CS) may develop carcinoid heart disease (CaHD). However, the prevalence and health care resources to manage CaHD are not well understood. This study investigated the prevalence and economic burden of CaHD among adults with CS in the United States. METHODS: This retrospective study analyzed insurance claims of patients with CS initiating somatostatin analogue (SSA) therapy. Eligible patients had ≥1 medical claim for CS with continuous insurance coverage for 1 year before and at least 30 days after initiating SSA therapy. Markers for CaHD were identified using a predetermined list of medical and/or procedural claims based on the clinical experience of a practicing cardiologist. Case subjects had a documented medical/procedural claim for a marker of CaHD during the study period; control subjects had no markers for CaHD. Baseline characteristics were assessed during the pre-SSA treatment initiation period. Economic outcomes (health care resources and expenditures) were assessed in the follow-up period after SSA treatment initiation and compared between incident case subjects and control subjects. Descriptive statistics were used to assess demographic and clinical characteristics. Univariate and multivariate models were used to assess differences in health care resource use and costs between case subjects and control subjects. FINDINGS: A total of 654 patients met the eligibility criteria; 248 (38%) had a prevalent marker of CaHD and were excluded from the economic analysis. The analytic sample included 406 patients with CS, 185 (46%) of whom had an incident CaHD marker (case subjects) and 221 were controls. Baseline characteristics between the case subjects and control subjects were similar with the exception that case subjects tended to be older. Average health care resource use and costs were higher among case subjects (total costs, $51,825 vs $29,068; P < 0.01), driven by average hospital admissions (1.4 vs 0.7) with increased length of stay (4.3 vs 2.0 days), office visits (22.8 vs 19.8), and outpatient services (22.3 vs 15.4; all, P < 0.05). IMPLICATIONS: CaHD may be common among patients with CS before initiating SSA therapy and within 2 years of starting SSA therapy, suggesting suboptimal control of serotonin production. Patients with CaHD incur substantial economic costs in addition to the clinical morbidity compared with patients with CS and no CaHD.

TELEPRO: Patient-Reported Carcinoid Syndrome Symptom Improvement Following Initiation of Telotristat Ethyl in the Real World.

BACKGROUND: When carcinoid syndrome (CS) diarrhea (CSD) is inadequately controlled with long-acting somatostatin analogs (SSAs), clinical practice guidelines recommend addition of the tryptophan hydroxylase inhibitor telotristat ethyl (TE). In a 12-week multinational, randomized controlled trial, TE added to SSA reduced peripheral serotonin and the frequency of CSD. We evaluated real-world effectiveness of TE using patient-reported data from a nurse support program over 3 months. MATERIALS AND METHODS: This study used a deidentified data set of patients initiating TE who opted into a nurse support program between March and November 2017 and reported CS symptom burden at baseline and at least one follow-up time point at months 1, 2, and 3. Patients reported demographic and medical history information as well as frequency of bowel movements (BMs) and flushing episodes, severity of nausea, urgency and abdominal pain (0 "no/not at all" to 100 "worst imaginable/very urgent"), and stool form (1 "very hard" to 10 "watery"). Mean changes from baseline in CS symptom burden were reported using paired-sample t tests and Wilcoxon signed-rank tests. RESULTS: Most patients initiating TE enrolled in the nurse program (791/898, 88%), of whom 369 (47%) were included in the analysis. Patients treated with TE reported significant reductions in CSD and other CS symptoms (all p < .001). At least half of patients treated with TE experienced ≥30% improvement from baseline in BM frequency and an average reduction of at least two BMs per day within 3 months. CONCLUSION: Patients taking SSA therapy showed substantial burden of disease before initiating TE and significant improvements with the addition of TE treatment in this real-world effectiveness study. IMPLICATIONS FOR PRACTICE: Patients with carcinoid syndrome diarrhea uncontrolled by high doses of long-acting somatostatin analogs may be candidates for additional therapy with the tryptophan hydroxylase inhibitor telotristat ethyl. Understanding the real-world prevalence of uncontrolled symptoms and the effectiveness of telotristat ethyl in clinical practice may further support clinical and policy decisions for these patients. This study investigated self-reported carcinoid syndrome symptom burden and improvements among patients initiating telotristat ethyl and participating in a voluntary nurse support program. Disease burden and off-label somatostatin analog treatment before initiating telotristat ethyl were high, and symptoms improved markedly over 1, 2, and 3 months of treatment.

Carcinoid Heart Disease: Review of Current Knowledge.

Carcinoid heart disease is the collective term for all cardiac manifestations in patients who have carcinoid syndrome. Carcinoid heart disease has a multifactorial pathophysiology, and the right side of the heart is usually involved. Symptoms and signs vary depending upon the affected cardiac components; most typical is right-sided heart failure secondary to diseased tricuspid and pulmonary valves. Despite no single ideal diagnostic test, strong suspicion, coupled with serologic and imaging results, usually enables diagnosis. Advances in imaging, such as speckle-tracking echocardiography and cardiac magnetic resonance, have improved the diagnostic yield. Treatment is challenging, warrants a multidisciplinary approach, and can be medical or surgical depending on the cardiac manifestations. Investigators are exploring the therapeutic use of monoclonal antibodies and new somatostatin analogues. In this review, we cover current knowledge about the pathophysiology, diagnosis, and treatment of carcinoid heart disease.

Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome.

BACKGROUND: Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. SUBJECTS, MATERIALS, AND METHODS: Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. RESULTS: Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. CONCLUSION: Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. IMPLICATIONS FOR PRACTICE: Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.

Cutaneous Metastasis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-Nets).

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors are neoplasms commonly found within the gastrointestinal tract that originate from endocrine cells. These are slow progressive tumors and often metastasize to other elements of the gastrointestinal tract including the liver. Consequently, these tumors release hormones including serotonin and/or histamine that are responsible for the symptoms including intermittent flushing and diarrhea. Metastasis of gastroenteropancreatic neuroendocrine tumors, although rare, is possible and may extend to local lymph nodes and viscera. CASE REPORT: Our patient was a 69-year-old female who initially presented with postprandial abdominal pain, nausea, vomiting, and later was diagnosed with gastroenteropancreatic neuroendocrine tumors following surgical resection in 2014. Restaging after surgery showed regional lymph node involvement and hepatic metastasis. Of note she did not have a pre-operative computed tomography scan. She was started on octreotide, and later switched to lanreotide. In the interim, she did not have any positive findings on serial octreoscans depicting the skin lesion that was performed in the interim period every six months. However, she noticed a cutaneous mass in the upper right flank mass in 2016, which was followed up by a dermatologist. In 2017, the mass grew in size and hence biopsied which showed neuroendocrine tumors consistent with her primary tumor. DISCUSSION: Gastroenteropancreatic neuroendocrine tumors often metastasize to lymph nodes and liver but rarely can involve the skin and present as firm papules as found in our patient. Cutaneous metastasis of gastroenteropancreatic neuroendocrine tumors often has high morbidity and mortality and is usually associated with a primary lesion in the bronchopulmonary system. However, as demonstrated in this case report, cutaneous metastasis can originate from the gastrointestinal tract, including the small intestine as well.

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.

Quadruple valve replacement for carcinoid heart disease

Abstract Introduction: Carcinoid heart disease most frequently involves the tricuspid or, more rarely, the pulmonary valve and presents with right heart failure as 5-HT is metabolized by the lung. Left-sided valve involvement is quite rare. We describe our experience of 3 patients presenting with heart failure secondary to carcinoid heart disease affecting all four cardiac valves. There are only four previous isolated case reports in the literature. Methods: All three patients underwent quadruple valve replacement during a single operation. Right ventricular outflow tract reconstruction with a pericardial patch was performed in all patients. For 24 hours prior to surgery, all patients received intravenous octreotide, which continued in intensive care for at least 24 hours. Results: Mean cross-clamp and bypass times were 175 (range 164-197 minutes) and 210 (range 195-229 minutes) minutes, respectively. Mean intensive treatment unit (ITU) and inpatient stays were 2.3 (range 2-3 days) and 12 (range 9-16 days) days, respectively. One patient was reopened for bleeding 4 hours postoperatively from a ventricular pacing wire site. None required a permanent pacemaker postoperatively. There were no other complications in any patient. The quality of life was excellent at 6-16 months clinic follow-up as they were in NYHA 1. Postoperative echocardiography showed no paravalvular leaks and well-functioning prostheses in all cases. Conclusion: Surgery to replace all four valves is feasible with excellent medium-term survival and a very low rate of complications. Patients with carcinoid heart disease should always be considered for surgery irrespective of the extent of valvular involvement.

Antidepressants appear safe in patients with carcinoid tumor: Results of a retrospective review.

INTRODUCTION: Patients living with neuroendocrine tumors have high rates of depression, often necessitating antidepressants, including selective serotonin reuptake inhibitors (SSRI). Neuroendocrine tumors (NETs) secrete vasoactive substances, including serotonin, which contribute to the cluster of symptoms known as carcinoid syndrome (flushing and diarrhea). Controversy exists over whether or not antidepressants are safe in NET. We aimed to study the safety of antidepressant use in NET patients. METHODS: We conducted a retrospective chart review of patients with well differentiated NET who were also prescribed antidepressants from January 2008 through April 2015. The study took place at Memorial Sloan Kettering Cancer Center and was approved by the hospital's institutional review board. RESULTS: Ninety-two patients were included. There were 16 (17.4%) patients with carcinoid syndrome (10 ileum, 1 duodenum, 1 jejunum and 4 unknown primary); and 76 (82.6%) patients without (41 lung, 9 pancreas, 8 ileal, 5 duodenum, 5 appendix, 2 unknown primary, 1 jejunum and 5 other). Median duration of antidepressant prescription was 11.6 months (range, 0-121) among those with carcinoid syndrome (N = 16) and 14.3 months (range, 0-172) among those without carcinoid syndrome (n = 76). Antidepressants were stopped in 31 cases (33.7%), though the reason was not specified in the majority of cases (n = 18; 58%). None of the patients developed carcinoid syndrome while being prescribed antidepressants. No patients developed carcinoid crisis. CONCLUSION: Our findings do not support previous authors' recommendations that SSRIs must be avoided in NET patients. Several classes of antidepressants appeared safe in NET patients with and without carcinoid syndrome.

Clinical study of umbilical compress using anti-cancer Xiaogu formula in the management of malignant ascites / 国际中医中药杂志

Objective To observe the clinical efficacy of umbilical compress with anti-cancer Xiaogu formula in managing malignant ascites. Methods A total of 56 patients with malignant ascites who met the inclusion criteria were randomized into 28 patients in the treatment group and 28 patients in the control group. The control group was treated with one type of diuretic, and the treatment group was given umbilical compress using Anti-Cancer Xiaogu formula and diuretics. Both groups were treated for 14 days. The changes of abdominal girth, 24 h urine volume, ascites efficacy, TCM syndrome scores, quality of life and adverse reactions were observed. Results The decrease in the maximum depth difference of the ascites in the treatment group was significantly greater than that of the control group (1.16 ± 1.29 vs. 0.00 ± 1.34, Z=-2.553). The difference was statistically significant (P<0.05). The decrease in abdominal girth in the treatment group was significantly larger than that in the control group (0.57 ± 0.55 vs. 2.61 ± 0.28, Z=-2.264). The difference was statistically significant (P<0.05). The in 24-hour urine volume in the treatment group after intervention (-800.18 ± 64.12 vs.-683.57 ± 55.38, Z=-1.770) was no statistically significant (P>0.05). The response rate in the treatment group was 92.9％ (26/28), while that of the control group was 89.3％ (25/28).treatment group was 71.4％, while that of the control group was 35.7％. The difference was statistically significant (P<0.05). The increase in KPS in the treatment group was significantly higher than that of the control group. The difference was statistically significant (P<0.05). Conclusions Anti-cancer Xiaogu umbilical cord combined with diuretic can reduce the degree of malignant ascites, alleviate clinical symptoms, improve quality of life and decrease the occurrence of adverse reactions when used concomitantly with diuretics in the management of malignant ascites.

Tratamiento quirúrgico de la enfermedad metastasica del síndrome carcinoide: hepatectomía parcial usando un bypass veno-venoso y posterior cambio valvular tricúspide. Reporte de caso / Surgical treatment of carcinoid syndrome metastatic disease: Partial hepatectomy with veno-venous bypass and subsequent tricuspid valve replacement. Case report

Abstract Introduction: Carcinoid syndrome is a relatively rare condition that may affect the liver and the right heart. Some of these cases may require surgical treatment with a multidisci-plinary approach. Case report: We report the case of a patient with progressive dyspnoea, arterial hypotension and facial flushing, diagnosed with liver and cardiac involvement from carcinoid syndrome. The patient was taken to surgery in two different occasions, first for metastatic liver resection, and then to subsequent cardiac surgery for tricuspid valve replacement. Conclusions: We report here a case review, including the clinical course, the intra-operative management, and the information available in the literature regarding which procedure to perform initially in these types of cases which are not very common in clinical practice.

Resumen Introducción: El síndrome carcinoide es una condición relativamente rara que puede afectar el hígado y el corazón derecho. En algunos pacientes se requiere tratamiento quirúrgico y un manejo multidisciplinario. Presentación del caso: Presentamos una paciente con diagnóstico de síndrome carcinoide con compromiso hepático y cardíaco, quien inició con disnea progresiva hasta el reposo, hipotensión arterial y rubor facial. La paciente fue llevada a cirugía en dos tiempos: la resección de las metástasis hepáticas inicialmente y, en un segundo tiempo, cirugía cardíaca para el cambio de la válvula tricúspide. Ambas intervenciones se realizaron con éxito y sin complicaciones. Conclusión: Presentamos aquí una revisión del caso, la evolución y el manejo intraoperatorio y la información disponible en la literatura para decidir qué procedimiento se debe realizar en primera instancia, ya que estos casos no son frecuentes en la práctica clínica.