Metastatic Carcinoid Tumor Research Articles

Laparoscopic hand-assisted enucleation of symptomatic metastatic multifocal carcinoid tumor of the liver (with video)

Laparoscopic hand-assisted enucleation of symptomatic metastatic multifocal carcinoid tumor of the liver (with video)

Current Consensus on I-131 MIBG Therapy.

Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.

Just another metastatic carcinoid tumour to the uveal tract

We describe the clinic, image, and histopathologic features of a well differentiated neuroendocrine carcinoma (carcinoid tumour) metastatic to choroid and ciliary body in a 52-year-old Mexican Mestizo man. The ophthalmologic examination showed an inferior choroidal mass accompanied by exudative retinal detachment. Ultrasound B-Scan study revealed a diffuse thickened choroid with overlying serous retinal detachment, ultrasound A-Scan revealed a high internal reflectivity solid lesion. Ultrasound biomicroscopy (UBM) evidenced a dome shaped ciliary body mass, presumptive diagnosis was uveal tract metastatic disease. Scleral flap choroidal incisional biopsy was performed. Microscopic evaluation demonstrated a hypercellular lesion replacing choroid, composed by cohesive oval-round cells with finely granular chromatin arranged in organoid pattern. Immunohistochemical reactions were Pankeratin AE1/AE3 (+), Cytokeratin CK5/6 (+), Chromogranin A (+), Ki67 (20%), typical well differentiated neuroendocrine carcinoma (carcinoid tumour) was diagnosed. Patient had a mediastinal carcinoid diagnosed 3 years earlier. Metastatic cancer to the eye is perhaps the leading cause of intraocular tumour, despite this fact metastases are rarely seen by the ophthalmologist while the patient is alive. Intraocular metastasis should be considered in the presence of ciliary body or/and choroidal amelanotic or pigmented mass and serous retinal detachment in a patient with history of carcinoid tumor, althought its low frequency (2.2%).

Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary

Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995–2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33–83 years), including 9 primary (median age 68 years, range 33–73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36–83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6–8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3–46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.

Triple Valve Replacement in a Rare Case of Left-sided Carcinoid Heart Disease

Carcinoid heart disease (CHD) is characterised by plaque-like deposits of fibrous tissue on the endocardium as a result of production of vasoactive substances by carcinoid tumours. CHD typically affects the right-sided valves of the heart. Involvement of the left-sided valves rarely occurs, as it is thought that the pulmonary circulation inactivates the vasoactive substances. Left-sided CHD has been reported in patients with a patent foramen ovale and/or bronchial carcinoid lesions. We present a rare instance of left-sided CHD, occurring without an intracardiac shunt or bronchial carcinoid lesions. This 66-year-old male was diagnosed with a metastatic small bowel carcinoid tumour with liver metastases in 2014, and was managed with lanreotide injections. He was found to have CHD involving his tricuspid, pulmonic, and aortic valves. Initially, he was medically managed; however, following multiple presentations and worsening heart failure he was referred for surgical management. A successful elective triple valve replacement (and one coronary artery bypass grafting) was performed, with replacement of the tricuspid, pulmonary, and aortic valves with bioprosthetic valves. Histology of the resected valves was suggestive of chronic carcinoid valvulopathy. At a 2-month follow-up appointment after his surgical admission his heart failure symptoms had improved markedly. There are very few case reports in the literature documenting management of left-sided CHD and the pathophysiology is not well established. All valves should be assessed and patients with CHD should be undergo close surveillance, with consideration of valvular surgery in patients with severe valvular dysfunction to potentially improve prognosis and long-term functional status.

Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors

Recently, there has been a move toward decreasing the threshold for liver debulking for metastatic carcinoid tumors from 90% to 70%. The debulking threshold and factors that predict outcomes of liver debulking operations specifically among pancreatic neuroendocrine tumors are not well defined. Records of patients with pancreatic neuroendocrine tumors undergoing liver debulking with a threshold of 70% from 2006 to 2016 were reviewed. Extrahepatic metastases and positive margins by enucleation were allowed. Liver progression-free survival and overall survival were calculated by the Kaplan-Meier method for various factors and compared by log-rank. Factors also were correlated with liver progression-free survival and overall survival by multivariate regression analyses. Forty-two patients underwent 44 operations, of which 24 resulted in 100% debulking, 12 resulted in ≥90% debulking, and 8 resulted in ≥70% debulking. Median liver progression-free survival was 11 months. The 5-year overall survival rate was 81%. There were no significant differences in outcome based on percent debulked. Only liver metastasis ≥5 cm correlated with liver progression-free survival and overall survival. Consideration should be given to expanding the criteria for liver debulking in pancreatic neuroendocrine tumors to include a new threshold of >70% debulking, intermediate grade tumors, positive margins, and extrahepatic metastases; these criteria yield results indistinguishable from complete resection. Using these expanded criteria will increase the number of patients eligible for an operation and maintain high survival rates.

Metastatic carcinoid tumor with severe double valve disease at diagnosis: Case report and review of literature

A 27-year-old woman with a history of anxiety presented with three months of diarrhea. Onphysical examination, she had a grade 3/6 systolic heart murmur at the lower left sternal borderwhich increased with inspiration, a grade 2/6 decrescendo diastolic murmur at the left sternalborder, and lower extremity edema. Stool studies were negative. The abdominal ultrasounddemonstrated multiple complex liver cysts. Transthoracic echocardiogram reported tricuspidvalvular thickening with stenosis and regurgitation, severe pulmonary stenosis, and mild aorticregurgitation with valvular thickening. 5-hydroxyindole acetic acid and chromogranin A levelswere elevated. The patient’s symptoms improved after octreotide therapy, and she underwenttricuspid and pulmonary valve replacement.The incidence of carcinoid tumors is 1.2 to 2.1 per 100,000 people in the general population.Carcinoid heart disease occurs in one-half to two-thirds of patients with carcinoid syndromeand is associated with poorer clinical outcomes. Left side cardiac involvement occurs in lessthan 10% of patients. The presence of both left and right sided valvular disease in the contextof gastrointestinal carcinoid is associated with severe and poorly controlled disease. Up to4% of these cases have metastatic disease on the valves, and 3.8% have direct myocardialinvolvement.

OR33 The importance of detection of donor-chimerism and anti-donor or anti-recipeint HLA antibodies after liver-contained intestinal transplantation

Acute graft versus host disease (aGvHD) is a devastating complication of transplantation, with the highest incidence after liver-contained intestinal transplantation (LIT). Its prompt diagnosis with analysis of involved cell components is critical for treatment plan. Here we present two aGvHD cases after LIT, diagnosed with donor-chimerism by short tandem repeat assay along with detection of de novo anti-recipient or donor specific HLA antibodies (dRSA or dDSA). Case 1 : A 2-year girl presented with skin rash, and fever 2 weeks after LIT for trichohepatoenteric syndrome. On post operative day (POD) 15, donor-derived CD8 cell was detected with 60%, and peaked on POD 20 (74% CD8, 91% CD19) (Fig. 1A). Importantly, multiple dRSAs were also detected (Fig. 1B). The diagnosis of combined cellular and humoral aGvHD elicited anti-B cell therapy with bortezomib/rituximab. Subsequently, all dRSAs but DQ8 declined to Case 2: A 41-year man developed acute cellular rejection a week after LIT for metastatic carcinoid tumors. Rejection was resolved with thymoglobuline treatment, but DQ2 dDSA persisted on POD 31-100. Along with skin rash, donor-chimerism was detected on POD 62 (45% CD8, 53% CD19), and persisted for the next 40 days with absence of dRSA. Accordingly, cellular aGvHD was treated with photopheresis and steroid, with significant reduction of both DQ2 dDSA and donor-chimerism (Fig. 1C and D). After resolution of aGvHD, he developed intra-abdominal sepsis from surgical complication and died on POD 200. Simultaneous occurrence of aGvHD and circulating dDSA reflects lymphocyte reactivity from both recipient and donor. Even though both patients succumbed due to complicated courses, donor-chimerism and HLA antibody detection provided critical information of donor-derived T and B cell involvement that guided treatment plan for dRSA, dDSA, and aGvHD.

The Role of PET Scanning in the Evaluation of Patients With Kidney Disease.

Patients with underlying kidney disease are often required to undergo imaging for a variety of purposes including diagnosis and prognosis. A test that is being increasingly used with for this group of patients is the positron emission test (PET) scan. In addition, combining the nuclear medicine technique (PET) with computed tomography scan allows additional imaging advantages over either alone. These imaging modalities are commonly used for a number of extrarenal indications (ie, cancer, coronary artery disease, central nervous system disease, infectious diseases, and others). They have also been used for diagnosis of acute tubulointerstitial nephritis, evaluation and management of retroperitoneal fibrosis, identifying infection within kidney and liver cysts, and distinguishing complex kidney cysts from kidney cancer in patients with underlying CKD. We will review PET scan utility in patients with kidney disease.

Asymptomatic Metastatic Carcinoid Tumor Discovered by Routine Screening Mammography

Asymptomatic Metastatic Carcinoid Tumor Discovered by Routine Screening Mammography

A Rare Case of Widely Metastatic Carcinoid Tumor with Lymphovascular Hepatic Invasion and Carcinoid Heart Disease

A carcinoid tumor's clinical symptoms can be divided into three categories, including local effect from tumor mass, carcinoid syndrome, and fibrotic reaction. Without vascular invasion, carcinoid syndrome symptoms of flushing, diarrhea, and bronchospasm are uncommon, accounting for less than 10 percent of patients. However, carcinoid syndrome incidence increases to around 50 percent when liver metastases and vascular invasion are present. We report the rare case of a carcinoid tumor exhibiting local mass effect from liver metastases, carcinoid heart disease from fibrotic reaction, and rare bone metastases, without any symptoms of carcinoid syndrome despite lymphovascular hepatic invasion. A 45 year old male with a history of heavy alcohol abuse, tobacco abuse and depression was evaluated for worsening right upper quadrant pain, early satiety, and a 30 pound weight loss over the past 2 months. Laboratory investigation revealed AST of 883 and ALT of 1051 and a modestly elevated bilirubin. Computed tomography (CT) three phase scan of the liver and pelvis demonstrated innumerable solidly and peripherally enhancing hepatic lesions, ascites, bilateral pleural effusions, and a mass-like ileocecal valve. Liver biopsy revealed well differentiated neuroendocrine tumor positive for lymphovascular invasion. Octreotide scan demonstrated radiotracer activity in the left skull base, numerous vertebrae including C2, T2, mid and lower thoracic vertebrae, L4, sacrum, right scapula, multiple ribs, liver, and ileocecal valve. 24 hour urine studies confirmed a 5-HIAA level of more than 6 times normal and serum chromogranin A more than 5 times normal. Transthoracic echo showed wide open tricuspid regurgitation, severe aortic and pulmonic regurgitation, and thickened anterior and posterior mitral valve leaflets. Due to the patient's decompensated state, he was not deemed a candidate for chemotherapy, placed on hospice, and passed away several weeks later. This case underscores the significance of recognizing the range of clinical and pathophysiological symptoms which arise from a metastatic carcinoid tumor. The ability to detect advanced disease such as local mass effect or carcinoid heart disease without features of carcinoid syndrome remains at the crux of physician care, such that treatment options for patients can be explored in the future.

Multiple liver-directed therapy including theraspheres for recurrent metastatic jejeunal carcinoid tumor

Multiple liver-directed therapy including theraspheres for recurrent metastatic jejeunal carcinoid tumor

Evaluation of the combination of oxaliplatin and 5-fluorouracil or gemcitabine in patients with sporadic metastatic pulmonary carcinoid tumors

ObjectivesThe aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors. Patients and methods45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1–5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m2 and oxaliplatin 100mg/m2 every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m2 in bolus injection and 5-FU 2400mg/m2 in 46h-infusion) and oxaliplatin 85mg/m2 (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8–12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves. ResultsPatients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1–12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6–25) months. Median overall survival (OS) was 34 (21–49) months. No significant difference was observed in response and PFS between either regimens. ConclusionsOur results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.

Metastatic Carcinoid Tumor Presenting as a Breast Mass: A Case Report and Review of the Literature

Carcinoid tumors are indolent neoplasms derived from the enterochromaffin cells which have a wide anatomic distribution. Most common primary sites include gastrointestinal tract and bronchopulmonary system. Despite their slow growing nature, carcinoid tumors possess metastatic potential, and breast is a rare but known site of metastasis. We report a case of breast metastasis from carcinoid tumor of the terminal ileum in a 53 year old woman who initially presented with a breast mass detected by screening mammography. A review of literature was performed for this rare presentation of breast as the initial site of detection of metastatic carcinoid tumor.

Adult intussusception in diffuse large B-cell lymphoma following chemotherapy: A case report and literature review

Secondary adult intussusception is associated with a pathological condition involving a lead point, including malignant tumors such as a primary or metastatic adenocarcinoma, GIST, leukemia, lymphoma, or carcinoid tumor. Thirty percent of small intestine intussusception was caused by malignancy. Most of these malignancies were metastases, while primary small intestinal malignancy were rare. Intussusception in lymphoma patients has been reported, with predominant location of intussusception in the ileo-colica region. Intussusception occuring after chemotherapy has been reported in four cancer patient following chemotherapy, but no report about this condition in lymphoma patient. A 44-year-old female patient with DLBCL was diagnosed of intussusception eight days after the initiation of chemotherapy. Plain abdominal radiology and CT scan confirmed intussusception on the ileo-colica region. No surgical intervention was done due to the condition of the patient. This is the first reported case of inssusception in a DLBCL patient that had undergone chemotherapy for the lymphoma.

Carcinoid Syndrome-Induced Ventricular Tachycardia.

Introduction. Carcinoid tumors are rare neuroendocrine malignancies that secrete multiple bioactive substances. These bioactive substances are responsible for the carcinoid syndrome characterized by diarrhea, flushing, syncope, and right-sided valvular heart disease. Previous case reports have described carcinoid syndrome associated with coronary vasospasm and the well-characterized carcinoid heart disease. Case. Our patient is a 73-year-old female with complex past medical history most notable for metastatic carcinoid tumors diagnosed in 2013-05. She initially presented in 2014-09 with syncope and dizziness associated with sinus pause on an event monitor. She received a pacemaker given normal left ventricular function and was discharged. However, she was readmitted with similar symptoms corresponding to multiple episodes of ventricular tachycardia. She was started on high-dose beta blockade and has had no recurrence of arrhythmia over a follow-up period of 12 months. Conclusion. We hypothesize that the patient's ventricular tachycardia was mediated by the multiple bioactive substances secreted by her carcinoid tumors. Her carcinoid tumor biomarkers were elevated and other explanations for arrhythmia were investigated and ruled out. To our knowledge, this is the first case of ventricular tachycardia mediated by carcinoid syndrome and suppressed by beta-blocker. Further investigation into this relationship is needed.

The histological rarity of thyroid cancer

AbstractThyroid cancer is the most common endocrine cancer, accounting for about 1% of all cancers. Sarcomas, lymphomas and metastases to the thyroid gland are rare and only with a handful of descriptions in the literature.Objective: To describe rare histological types of thyroid cancer found in a reference center.Methods: Medical chart review from admitted patients diagnosed with thyroid cancer in the period from 1977 to 2010. Demographic, diagnostic, therapeutic and histopathological information were collected.Results: 3,018 records of patients admitted with thyroid disease were reviewed. Among the cases diagnosed with rare tumors there was a predominance of: anaplastic carcinoma: 22 cases (0.7%), followed by 11 cases of medullary carcinoma (0.36%); 2 cases of sarcoma (0.07%), 2 cases of lymphoma (0.07%) and one case of metastatic carcinoid tumor (0.03%). There were more females diagnosed (57%) as well as Caucasians (84%). The most frequent clinical presentation was a palpable thyroid nodule. All patients with lymphoma, sarcoma and anaplastic carcinoma died.Conclusion: Sarcomas, lymphomas and thyroid metastases are uncommon and tend to worse outcomes.

A Rare Case of Hormonally Inactive Asymptomatic Metastatic Carcinoid Tumor of the Small Bowel

A Rare Case of Hormonally Inactive Asymptomatic Metastatic Carcinoid Tumor of the Small Bowel

Metastatic Carcinoid Tumor to Bilateral Breasts Mimicking Primary Low-Grade Invasive Ductal Carcinoma: An Impact on Patient Care

Metastatic Carcinoid Tumor to Bilateral Breasts Mimicking Primary Low-Grade Invasive Ductal Carcinoma: An Impact on Patient Care

Rapid octreotide separation from synthetic peptide crude mixtures by chromatography on poly(styrene–co-divinylbenzene)-based reversed phases

Octreotide, a disulfide-cyclized eight amino acids long analogue of somatostatin, has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and vasoactive intestinal peptide secreting adenomas (watery diarrhea). As composed by D-amino acids, C-terminal alcohol, and disulfide bond, octreotide can be only prepared using chemistry synthesis method, which increases difficulty of the traditional reversed-phase separation. In this paper, we report a very fast separation of octreotide from synthetic peptide crude mixtures on a poly(styrene co-divinylbenzene) (PSt)-based reversed phases prepared by a quick membrane emulsification process. In general, fourier-transformed infrared resonance (FT-IR) spectroscopy, reversed-phase high performance liquid chromatography (HPLC) combined with electrospray ionisation mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR) spectroscopy are routinely used for analyses of resultant peptides. Under the optimized conditions, the octreotide is purified from 42.89% to 99.99%. Consequently, the poly(styrene co-divinylbenzene)-based phase can provide more flexibility to improve separation efficiency for the octreotide from the synthetic peptide crude mixtures. (C) 2015 Elsevier B.V. All rights reserved.