Oncological use of anti-angiogenic VEGF inhibitors has been limited by the lack of informative biomarkers. Previously we reported circulating Tie2 as a vascular response biomarker for ...bevacizumab-treated ovarian cancer patients. Using advanced MRI and circulating biomarkers we have extended these findings in metastatic colorectal cancer (n = 70). Bevacizumab (10 mg/kg) was administered to elicit a biomarker response, followed by FOLFOX6-bevacizumab until disease progression. Bevacizumab induced a correlation between Tie2 and the tumor vascular imaging biomarker, K
(R:-0.21 to 0.47) implying that Tie2 originated from the tumor vasculature. Tie2 trajectories were independently associated with pre-treatment tumor vascular characteristics, tumor response, progression free survival (HR for progression = 3.01, p = 0.00014; median PFS 248 vs. 348 days p = 0.0008) and the modeling of progressive disease (p < 0.0001), suggesting that Tie2 should be monitored clinically to optimize VEGF inhibitor use. A vascular response is defined as a 30% reduction in Tie2; vascular progression as a 40% increase in Tie2 above the nadir. Tie2 is the first, validated, tumor vascular response biomarker for VEGFi.
Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical ...trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the ...clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months 95% CI 15.2–31.3; median time to death from BMs diagnosis was 3.0 months 95% CI 0.0–8.3. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Objective
Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan ...localise and stage disease. This study aimed to evaluate the complementary role of
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Gallium (
68
Ga)-DOTA PET/CT in managing patients with panNETs.
Design
A retrospective study conducted across three tertiary UK NET referral centres.
Methods
Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a
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Ga-DOTA PET/CT scan for a suspected panNET.
Results
We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1
vs.
9.3% (n=163 vs. 17) alive
vs.
dead (3 data missing), 141 sporadic
vs.
42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional
vs.
functional tumours comprised 73.2
vs.
21.3% (n=134
vs.
39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224
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Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall,
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Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases.
Conclusion
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Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.
The incidence of neuroendocrine neoplasms (NENs) is increasing, especially for patients with early stages and grade 1 tumours. Current evidence also shows increased prevalence, probably reflecting ...earlier stage diagnosis and improvement of treatment options. Definition of adequate postsurgical follow-up for NENs is a current challenge. There are limited guidelines, and heterogeneity in adherence to those available is notable. Unfortunately, the population of patients at greatest risk of recurrence has not been defined clearly. Some studies support that for patients with pancreatic neuroendocrine tumours (PanNETs), factors such as primary tumour (T), stage, grade (Ki-67), tumour size, and lymph node metastases (N) are of relevance. For bronchial neuroendocrine tumours (LungNETs) and small intestinal neuroendocrine tumours (siNETs), similar factors have been identified. This review summarises the evidence supporting the rationale behind follow-up after curative resection in well-differentiated PanNETs, siNETs, and LungNETS. Published evidence informing relapse rate, disease-free survival, and relapse patterns are discussed, together with an overview of current guidelines informing postsurgical investigations and duration of follow-up.
Whats special in a child′s larynx? Prakash, Manoharan; Johnny, JCarlton
Journal of pharmacy & bioallied science,
2015, Volume:
7, Issue:
5
Journal Article
Peer reviewed
Open access
What′s special in a child′s larynx? Many of us know only a few specialties of the pediatric larynx, but there are much more features, which are unique and often not highlighted. To understand the ...pediatric larynx, we have reviewed the development, the functions in-utero and new born period and peculiarities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•There is a potential for integrating other imaging modalities in the management of pancreatic cancer.•Standard uptake values from 18F-FLT PET images have been shown to correlate with cellular ...proliferation in some malignancies.•18F-FLT PET in GI malignancies is limited by high physiologic radiotracer uptake in surrounding normal tissues and liver.•18F-FLT PET has higher specificity but lower sensitivity compared to 18F-FDG PET for measurement of cellular proliferation.•Dynamic imaging with 18F-FLT PET allows an improved understanding of treatment effects and detection of liver metastases.
Pancreatic ductal adenocarcinoma is known for its poor prognosis. Since the development of computerized tomography, magnetic resonance and endoscopic ultrasound, novel imaging techniques have struggled to get established in the management of patients diagnosed with pancreatic adenocarcinoma for several reasons. Thus, imaging assessment of pancreatic cancer remains a field with scope for further improvement. In contrast to cross-sectional anatomical imaging methods, molecular imaging modalities such as positron emission tomography (PET) can provide information on tumour function. Particularly, tumour proliferation may be assessed by measurement of intracellular thymidine kinase 1 (TK1) activity level using thymidine analogues radiolabelled with a positron emitter for use with PET. This approach, has been widely explored with 18F-fluoro-3′-deoxy-3′-l-fluorothymidine (18F-FLT) PET. This manuscript reviews the rationale and physiology behind 18F-FLT PET imaging, with special focus on pancreatic cancer and other gastrointestinal malignancies. Potential benefit and challenges of this imaging technique for diagnosis, staging and assessment of treatment response in abdominal malignancies are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Gingival fibromatosis is characterized by gingival tissue overgrowth of a firm and fibrotic nature. The growth is slow and progressive and is drug-induced, idiopathic, or hereditary in etiology. It ...occurs isolated or frequently as a component of various syndromes. Our patient presented with the complaint of gingival enlargement associated with progressive deafness, characteristic of Jones syndrome. This case report is important and unique since it is the first known one to have a Jones syndrome-like presentation without a family history. A male patient aged 14 years reported with the chief complaint of swelling of gums and progressive hearing loss in both ears for the past one year. There was no family history or history of drug intake. Enlargement was generalized, fibrotic and bulbous, involving the free and attached gingiva, extending up to the middle 1/3(rd) of the crown. Investigations such as pure tone audiogram, impedance audiometry, and Tone decay test concluded that there was severe right and moderate left sensorineural hearing loss. The case was diagnosed to be idiopathic, generalized gingival fibromatosis with progressive hearing loss. The gingival overgrowth was managed by gingivectomy and periodic review. The patient was advised to use high occlusion computer generated hearing aids for his deafness as it was not treatable by medicines or surgery. This unique case report once again emphasizes the heterogeneity of gingival fibromatosis, which can present in an atypical manner.
Rhinosporidiosis is a unique disease, which is seen to be endemic in certain places in India such as Tamil Nadu and Sri Lanka. The disease is caused by Rhinosporidium seebri and it is transmitted by ...bathing in ponds contaminated by cattle feces containing spores of the organism. The disease usually presents as multiple granulomatous bleeding polyps. The case described here is a unique presentation where it occurs only in a single site and that too in an uncommon location where the suspicion of rhinosporidiosis is a last possibility.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with ...first-line cisplatin-gemcitabine chemotherapy (current standard of care).
Methods
Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided.
Results
Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval CI = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16).
Conclusions
Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design.
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