Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Advances in the treatment of cytomegalovirus.

BACKGROUND: Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances. SOURCES OF DATA: Sources of data are recently published research papers and reviews about HCMV treatments. AREAS OF AGREEMENT: Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA. AREAS OF CONTROVERSY: Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection? GROWING POINTS: Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells. AREAS TIMELY FOR DEVELOPING RESEARCH: We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine.

Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein.

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases.

Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related.

Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells.

Human cytomegalovirus (HCMV) latency in the myeloid lineage is maintained by repressive histone modifications around the major immediate early promoter (MIEP), which results in inhibition of the lytic viral life cycle. We now show that pharmacological inhibition of histone deacetylases (HDACs) relieves this repression of the MIEP and induces transient expression of the viral lytic immediate early (IE) antigens but, importantly, not full virus reactivation. In turn, these latently infected cells now become targets for IE-specific cytotoxic T cells (CTLs) which are present at high frequency in all normal healthy HCMV positive carriers but would normally be unable to target latent (lytic antigen-negative) cells. This approach of transiently inducing viral lytic gene expression by HDAC inhibition, in otherwise latently infected cells, offers a window of opportunity to target and purge the latent myeloid cell reservoir by making these normally immunologically undetectable cells visible to pre-existing host immune responses to viral lytic antigens.

Sudden mono-ocular blindness with recurrent transient diplopia and ptosis in a middle-aged woman.

Sudden painless loss of vision is an ophthalmologic and a medical emergency resulting from various causes such as occlusion of retinal artery or vein, macular or vitreous haemorrhages, retinal detachment, and anterior and posterior ischaemic optic neuropathy. We report a 48-year-old woman presenting with right monocular blindness due to branch retinal artery occlusion whose vision recovered due to timely paracentesis coupled with treatment with adequate antiplatelet agents and anticoagulants. The patient had transient diplopia and ptosis despite adequate antiplatelet agents and anticoagulants. Thorough search for aetiology revealed the underlying cause to be aortoarteritis. Aortoarteritis is a rare disease, and ocular involvement occurs late in the disease. We review ophthalmologic manifestation of aortoarteritis and diagnostic utilities of various modalities for aortoarteritis.

Role of radionuclide scintigraphy in the detection of parathyroid adenoma.

BACKGROUND: Preoperative detection of parathyroid adenoma is a diagnostic challenge. The sonography and computerized tomography (CT) scan demonstrate high sensitivity but low specificity. The advent of radionuclide scanning technique has enhanced the specificity in this context. AIM: We undertook a study to assess the role of radionuclide scanning in suspected cases of parathyroid adenomas. MATERIALS AND METHODS: Totally 28 cases were incorporated in the study. The suspicion was raised either due to raised PTH levels or recurrent calcinosis. Most of these patients had estimation of calcium done as a routine or specific investigation. The parathyroid scan was performed using either of the two techniques - Dual isotope subtraction or Sestamibi washout technique. We also used the recent approach of fusion imaging (CT + tomographic nuclear images) in selected cases. RESULTS: There were 16 true positive, 10 true negative, 1 false negative and 1 equivocal scan findings. The findings were compared with sonography, CT Scan and PTH values. The true positive yield in our study was 57%, true negative 35% and the overall sensitivity and specificity was found to be 94% and 100% respectively. CONCLUSION: We conclude that parathyroid scintigraphy is a reliable and sensitive technique in the preoperative detection of parathyroid adenomas and should be the first choice of imaging modality in suspicion of parathyroid adenoma.

Dominance hierarchy and social grooming in female lion-tailed macaques (Macaca silenus) in the Western Ghats, India.

This article reports the structure of dominance and its relationship with social grooming in wild lion-tailed macaque females. The strength of dominance hierarchy was 0.79 on a scale of 0 to 1 indicating a moderate linearity in the ranking system. Dominance scores were converted into an ordinal as well as an interval scale. Grooming scores were also converted into interval scales using standard scores. Grooming received and grooming given correlated positively and negatively respectively with dominance ranks indicating that high ranking females received more and gave less grooming. Grooming was also positively related to encounter rates for dyads of females. More grooming among adjacent ranks, and grooming being more reciprocal, occurred only in the case of dominant females. The grooming patterns, therefore, appeared to be more of despotic than egalitarian nature. While ranking macaques into different Grades of social systems ranging from despotic to egalitarian, Thierry (2004) has placed lion-tailed macaques in Grade 3 corresponding to the 'relaxed' social system. Our results indicate that the grooming and dominance relationships in this species are more despotic, and hence, the Grade for this species requires to be shifted toward 2 or 1.

Population dynamics of a group of lion-tailed macaques (Macaca silenus) inhabiting a rainforest fragment in the Western Ghats, India.

We observed the overall population dynamics and number of births and deaths in identified individuals between January 2002 and October 2005, in a large group of lion-tailed macaques in the Anaimalai Hills of the Western Ghats in the south Indian state of Tamilnadu. The group inhabited an isolated rainforest fragment located inside a private tea/coffee garden. The group size increased from 56 in January 2002 to 84 in October 2005. All females reproduced, and the interbirth interval was 23.18 months. Of the 37 infants born between 2002 and 2005, only 1 died providing an infant survivorship rate of about 97.3%. Although births occurred in all months, most of the infants were born between February and March, and this pattern of births was consistent over the years, indicating a major birth peak in this species. The population growth rate in this unusually large group was found to be higher than even in those groups of lion-tailed macaques that inhabit large and relatively undisturbed rainforest complexes. This high growth rate could be attributed to the availability of abundant cultivated fruit plants including commercial crops such as coffee seeds. The observations provide a perspective for the management of other groups of this endangered species inhabiting rainforest fragments.

Pre and post betahistine therapy 99m Tc - HMPAO brain spect studies in patients with vertigo.

Vertebro basilar insufficiency (VBI) is a well known cause of vertigo. Brain Single Photon Emission Computed Tomography (SPECT) is an important diagnostic tool to detect and to quantitate the perfusion abnormalities in different areas of the brain. Effect of an antivertigo drug Betahistine on improving the hypoperfusion in different areas of the brain in vertigo patients was studied using brain SPECT. Betahistine at a dose of 16 mg three times daily was shown to improve perfusion in the hypoperfused areas of the brain resulting in relief from symptoms of vertigo. The cerebellar region, which is the most important area involved in vertigo patients with vascular pathology, showed almost complete normalisation of perfusion following Betahistine therapy.

Clinical utility of serum thyroglobulin in metastatic disease.

We examined the usefulness of serum thyroglobulin (Tg) levels in 196 patients with metastatic disease. Of these, 51 patients had a thyroidal primary (40 differentiated, 7 medullary and 4 undifferentiated), 35 patients had a nonthyroidal primary and in 110 patients the primary site was not known. Serum Tg was raised in 74.5 per cent (38 of 51) patients with carcinoma of the thyroid and in 92.5 per cent (37 of 40) patients with differentiated thyroid carcinoma (DTC). Twelve (34.3%) patients with proved nonthyroidal malignancies and 34 (30.9%) patients with unknown primary origin had elevated serum Tg levels. Of the 110 patients with unknown primary site thyroidal primary in 10 patients (all with elevated serum Tg levels) and nonthyroidal primary in 38 patients (7 had raised serum Tg levels) could be established. The sensitivity (for DTC) and the specificity (for nonthyroidal primary) of serum Tg estimation were 94.0 per cent (47 of 50) and 74.0 per cent (54 of 73) respectively and for patients with distant metastases were 100 (29 of 29) and 85.1 per cent (40 of 47) respectively. The positive and the negative predictive values of serum Tg were 71.2 (47 of 66) and 94.7 per cent (54 of 57) respectively and for patients with distant metastases were 80.6 (29 of 36) and 100 per cent (40 of 40) respectively. Our findings suggest that for patients presenting with metastases (particularly distant metastases) of an unknown primary site, serum Tg estimation is of great value to identify or rule out the involvement of the thyroid as the primary organ.

Left ventricular function in end stage renal disease--non-invasive assessment in patients on maintenance hemodialysis.

Non-invasive assessment of left ventricular function was performed by echocardiography and radionuclide ventriculography in 17 end-stage renal disease patients on maintenance hemodialysis. Patients with diabetes mellitus, ischemic heart disease and pericardial or valvular heart disease were excluded from the study. Parameters studied on echocardiography were left ventricular internal diameter in diastole (LVIDd), left atrial diameter (LAD), Aortic root diameter (ARD), Left ventricular posterior wall thickness in systole (LVPWs), End diastolic volume (EDV), End Systolic volume (ESV), fractional shortening percentage (FS%) and ejection fraction (EF). Parameters studied on radionuclide ventriculography were Peak ejection rate (PER), Peak filling rate (PFR) and Ejection fraction (EF). Significantly abnormal values for echocardiographic parameters LVIDd, LVPWs, EDV, ESV and FS% were found. On evaluation by MUGA scans, it was observed that the PER was significantly decreased while the PFR and EF did not change significantly.

Double primary neoplasms of the stomach and kidney.

We report a case of synchronous double primary neoplasms of the stomach and kidney. Immunohistochemistry confirmed the two primaries to be of different origin based on antigen expression.

Gastroesophageal reflux scintigraphy with radioactive capsules--a new technique for detection and quantitation of reflux.

A new technique for performing quantitative gastroesophageal scintigraphy has been described. The method involves administration of radioactivity in capsule form into the stomach; the isotope is released after dissolution of the capsule. The mean time of onset of capsule breakage was 3.3 min (range 2-5 min) and complete dissolution occurred by 6.0 min (range 5-8 min). The appearance of isotope activity in the oesophagus by means of cine scintigraphy was quantified by PDP 11/34 computer (Gamma-11) in terms of percentage of gastroesophageal reflux (GER). In 15 healthy subjects, the percentage of reflux (mean +/- S.D.) in the lower, middle and upper oesophagus was found to be 1.25 +/- 0.67, 0.26 +/- 0.23 and 0.02 +/- 0.04 respectively. We have studied 52 patients using this technique, and results are encouraging.

Clinical evaluation of 99mTc(V)-dimercapto succinic acid (DMSA) for imaging medullary carcinoma of thyroid and its metastasis.

99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12 (80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of 99mTc(V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of 99mTc(V)-DMSA (64.9%). In addition, 99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of 99mTc(V)-DMSA concentration in soft tissue and bone metastasis was similar.

Preparation and evaluation of 99mTc(V)-DMSA complex: studies in medullary carcinoma of thyroid.

Consequent to the promising results reported with 99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways: from freshly prepared reagents, through the use of a two component kit and use of the standard renal DMSA kit by a modified recipe. The 99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.

Serum thyroglobulin levels in patients with bone metastases from an unknown primary site.

Four cases with metastatic spread to bones and with primary site unknown are reported. The histopathologic examination on the bone biopsy material in 3 cases was adenocarcinoma. One case was suspected radiologically as primary bone tumor. The usefulness of estimation of serum thyroglobulin for detection of involved primary site is discussed.