Diagnosing and Managing Carcinoid Heart Disease in Patients With Neuroendocrine Tumors: An Expert Statement

Carcinoid heart disease is a frequent occurrence in patients with carcinoid syndrome and is responsible for substantial morbidity and mortality. The pathophysiology of carcinoid heart disease is poorly understood; however, chronic exposure to excessive circulating serotonin is considered one of the most important contributing factors. Despite recognition, international consensus guidelines specifically addressing the diagnosis and management of carcinoid heart disease are lacking. Furthermore, there is considerable variation in multiple aspects of screening and management of the disease. The aim of these guidelines was to provide succinct, practical advice on the diagnosis and management of carcinoid heart disease as well as its surveillance. Recommendations and proposed algorithms for the investigation, screening, and management have been developed based on an evidence-based review of the published data and on the expert opinion of a multidisciplinary consensus panel consisting of neuroendocrine tumor experts, including oncologists, gastroenterologists, and endocrinologists, in conjunction with cardiologists and cardiothoracic surgeons.     

Long-acting somatostatin analogues in the treatment of unresectable/metastatic neuroendocrine tumors

Neuroendocrine tumors (NETs) are a relatively rare and heterogeneous group of neoplasms with an annual incidence of ~35 cases per 100,000 people in the United States. The updated World Health Organization (WHO) classification system of gastroenteropancreatic (GEP)-NETs categorizes these tumors according to site of origin, clinical syndrome, and degree of differentiation. Well-differentiated NETs arising from the gastrointestinal tract or lungs (formerly known as carcinoid tumors) are often indolent and slow-growing. In contrast, poorly differentiated neuroendocrine carcinomas (NECs) are aggressive and have a poor prognosis. Due to their insidious onset, most NETs are diagnosed at an advanced stage and a curative approach is not possible. In these patients, medical therapy is limited to disease control, including relief of symptoms that arise from overproduction of peptide hormones by the tumors. Somatostatin analogues (SSAs) have remained the mainstay of symptoms control. In addition to symptoms control, clinical data also support an anti-proliferative effect of SSAs in patients with well- to moderately differentiated NETs. Long-acting SSAs have greatly facilitated their use. This review will focus on two long-acting SSAs, octreotide LAR and lanreotide, and their use in the clinical setting. Information necessary to assess their relative merits is summarized. We conclude these two therapies are interchangeable making value a very important consideration in their use.     

Estimation of Survival Rates of Breast Cancer Patients - a Hospital-based Study from Mumbai.

Purpose: To estimate the survival rates of breast cancer patients with reference to various factors like age, literacy status, residential status, T-stage and treatment. This is because there are very few studies reported from Indian subcontinent. Methods: Survival rates were obtained by using the actuarial method and loss-adjusted survival rate method (LAR) for the above factors and the rates were compared. The present study carried out at the Tata Memorial Hospital (TMH), includes newly diagnosed (who were not treated elsewhere before attending TMH) primary breast cancer patients and having completed the initial treatment. Results: The survival rates, actuarial survival and rates corrected for losses to follow-up (LAR) are presented. It showed that younger patients ( 50 years), with statistical significance ( p=0.024). There was no variation in survival with regard to the residential status but literate patients had a better ( non-significant) survival (77%) than their illiterate counterparts. T3-stage patients had the worst prognosis showing a 5-year survival of 60% (p=0.0002). Survival for those treated with surgery as the only modality and also in combination with other modalities did not show any remarkable differences except for the group that were treated with 'surgery in combination with chemotherapy'. The 5-year survival for those treated with surgery as the only modality was 83%. This study yielded useful information on breast cancer survival, especially in a situation with incomplete follow-up. The method applied (LAR) also clearly demonstrates the bias in estimates obtained by direct application of the standard actuarial method.     

Successful Therapy Using Pasireotide Long-acting Release for Cushing's Disease Merged with Biochemical Acromegaly

It is quite rare that Cushing''s disease shows acromegaly, and no pharmacotherapy has yet been discussed. A 21-year-old woman was diagnosed with Cushing''s disease and underwent trans-sphenoidal surgery. Five years later, she was diagnosed with recurrent Cushing''s disease and biochemical acromegaly because of elevated levels of serum growth hormone (GH), plasma insulin-like growth factor-1, plasma adrenocorticotropic hormone (ACTH), and the 24-hour urinary excretion of free cortisol. After treatment initiation with pasireotide-long-acting release (LAR), both the ACTH and GH declined. Our case is the first to show the efficacy of pasireotide-LAR in controlling both Cushing''s disease and acromegaly.     

Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12–15 months: A phase III,randomized, non-inferiority trial

BackgroundThe potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation.MethodsIn this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12–15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMR-RIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and anti-mumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT).ResultsEach formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (−10.94%) was beyond the pre-defined limit of −10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles.ConclusionsOne dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a non-inferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-year-old children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.     

直肠癌前切除、结肠“J”型储袋对术后排便功能的影响

目的为探讨直肠癌行低位前切除术后应用结肠“J”型储袋行直肠或肛管吻合能否改善患者的排便功能。方法对2000年1月至2001年1月间连续行低位前切除术的72例中、下段直肠癌患者行回顾性分析。根据吻合方式分为两组：“J”型储袋组,共33例;直接吻合组,共37例。分别于术后1、3、6及12个月,对手术并发症及排便功能行比较性研究。结果发现两组均无手术死亡及术后出血病例。直吻组发生吻合口瘘2例;储袋组及直肠组术后吻合口狭窄分别为2例及1例;局部复发者各为3例;肝转移分别为2例及3例。“J”型储袋组较直接吻合组患者术后6个月及12个月之日排便次数及夜间排便人数比率均明显减少（7次vs3次,P〈0．05;3次VS1次,P〈0．05）,（64％VS31％,P〈0．05;30％VS3．9％,P〈0．05）。前者大便失禁综合评分显著优于后者（8VS2,P〈0．05;5．2VSL5,P〈0．05）。结论结果表明直肠癌行低位前切除术后,应用“J”型储袋行直肠或肛管吻合,不增加手术并发症,且在术后1年内,可以在某些方面改善患者排便功能。