A Review of Primary Thyroid Lymphoma: Molecular Factors,Diagnosis and Management

Purpose/aim: To focus on current aspects of primary thyroid lymphoma (PTL), which is a rare clinical entity usually manifested by a rapidly growing mass in the neck that can cause pressure symptoms.

Materials and Methods: Relevant papers in PubMed published through June 2017 were selected to track updated information about PTL with an emphasis on diagnosis and novel therapeutic management.

Results: The most frequent cases include non-Hodgkin lymphoma derived from B-cells, mainly diffuse large B-cell lymphoma (DLBCL) followed by mucosa-associated lymphoid tissue (MALT) lymphoma or a mixed type. Other subtypes are less common. Lymphomas derived from T-cells and Hodgkin lymphomas are extremely rare. Hashimoto's autoimmune thyroiditis has been implicated as a risk factor for lymphoma. At the molecular level, the Wnt5a protein and its receptor Ror2 are involved in the course of the disease. Ultrasonography, fine needle aspiration (FNA) biopsy, and core or open biopsy combined with new diagnostic facilities contribute to an accurate diagnosis. An increased potential exists for a cure without the need for a radical surgical procedure. Modern chemoradiation therapy plus the monoclonal antibody rituximab, which acts against CD20, have limited the need for surgical interventions and provide an excellent outcome in most cases. However, some cases have resulted in treatment failure or recurrence.

Conclusions: A multidisciplinary approach must be used to define the management policy in each case. Future efforts by researchers are likely to be focused on the molecular level.     

Prolonged exposure of intraocular lens implant with preservation of globe integrity and visual function.

A 70-year-old woman had corneal ulcer and melting after complicated cataract surgery with polymethylmethacrylate lens implant insertion. A conjunctival flap was initially used to cover the defect with a plan to perform keratoplasty later. Fifteen months postoperatively, she presented with total absence of central corneal tissue and iris and exposure of the implant. The eye was not inflamed, painful, or hard on palpation and visual acuity was counting fingers at 3 m. The preservation of globe integrity despite exposure of the polymethylmethacrylate implant implies a stable adhesion between polymethylmethacrylate and residual corneal tissue and may prove useful in keratoprosthesis design.     

Her-2 protein expression, cellular localization, and gene amplification in colorectal carcinoma.

This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa=0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein.     

A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment.

BACKGROUND: Small series and retrospective studies have suggested that treatment with gemcitabine may be associated with pulmonary toxicity. However, a prospective evaluation of cancer patients treated with gemcitabine-based chemotherapy without neoplastic involvement of the thorax and without administration of radiotherapy has not been performed. PATIENTS AND METHODS: To investigate this issue, 41 consecutive patients receiving gemcitabine and carboplatin underwent prospective evaluation of lung function, which included pulmonary symptoms, pulmonary function tests, arterial blood gases and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with a substantial decline in diffusion capacity for carbon monoxide (DLCO), defined as a drop of > or = 20%, were reassessed 2 months later. RESULTS: After chemotherapy, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, alveolar volume or total lung capacity. In contrast, there was a significant decline in DLCO (73 +/- 22 versus 67 +/- 24% predicted; P = 0.017) and in carbon monoxide transfer coefficient (KCO) (89 +/- 24 versus 80 +/- 24% predicted; P = 0.004). Arterial blood gases did not change following treatment. Ten of the 41 patients (24%) exhibited a substantial decline in DLCO, which, however, recovered within 2 months (DLCO at baseline, immediately after therapy and at 2 months after completion of treatment, 84 +/- 14, 58 +/- 16 and 77 +/- 17% predicted, respectively; P < 0.001; baseline DLCO versus DLCO at 2 months, P > 0.05). Four of the 41 patients (10%) experienced dyspnea, which was self-limiting, with the exception of one patient who developed interstitial lung fibrosis. Among the various risk factors examined, older age, female gender and lower baseline DLCO were associated with more profound changes in DLCO post-treatment. CONCLUSIONS: This prospective analysis showed that the combination of gemcitabine and carboplatin induces a significant, but reversible, decrease in diffusion capacity, which is mostly asymptomatic. Thus, this regimen is safe as regards clinically significant lung toxicity.     

Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group.

BACKGROUND: In the present phase II multicenter study, we assessed the efficacy and tolerability of the combination of gemcitabine and carboplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic pancreatic cancer were treated with gemcitabine 800 mg/m(2) on days 1 and 8 and carboplatin at an AUC of 4 on day 8 of a 3-week cycle, for a total of six cycles. Primary end points were response rate and clinical benefit; secondary end points were, survival, time to progression (TTP) and toxicity. RESULTS: A total of 50 patients were enrolled in the study, 47 of whom were eligible for treatment. The median age was 63 years (range 34-76) and the median Karnofsky performance status (PS) was 80%. Patients received a median of six cycles (range 1-11). Among 35 patients evaluable for response, eight (17%) achieved partial response; 15 (32%) and 12 (25%) patients had stable and progressive disease, respectively. The median overall survival was 7.4 months; the median TTP was 4.4 months and the 1-year survival was 28%. The observed clinical benefit response was remarkable. After the second cycle of chemotherapy, 21 of 31 (68%) patients experienced pain improvement and reduced analgesic consumption. At the same time, 35% and 56% of our patients significantly improved their Karnofsky PS and weight, respectively. Overall, the treatment was well tolerated. The most common grade 3-4 toxicities were hematological, including 8% anemia, 6% neutropenia and 13% thrombocytopenia. CONCLUSIONS: The combination of gemcitabine plus carboplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer. This regimen has an acceptable toxicity profile and provides a significant clinical benefit, and hence warrants further investigation.     

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.     

Transjugular intrahepatic portosystemic shunt in cavernomatous portal vein occlusion

A 72-year-old patient with liver cirrhosis and cavernomatous portal vein occlusion presented with refractory ascites. We treated the patient with transjugular intrahepatic portosystemic shunt: transjugular transhepatic puncture of an intrahepatic hilar collateral vein was performed; transjugular intrahepatic portosystemic shunt was created between the right hepatic vein and the patent superior mesenteric vein using this hilar collateral vein as the connecting pathway. The ascites was resolved and the patient remains asymptomatic, while shunt patency is maintained 16 months after the intervention.     

Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR‐derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P < 0·001). The prevalence of CD was 32·9% in patients with T2* ≤ 8 ms, 12·5% in patients with T2* > 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14–20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.     

Diverse associations of microalbuminuria with C-reactive protein, interleukin-18 and soluble CD 40 ligand in male essential hypertensive subjects

BACKGROUND: Microalbuminuria (MA) and low-grade inflammation constitute emerging markers of subclinical atherosclerosis. We investigated whether urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), is associated with high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, and soluble CD40 ligand (sCD40L), in hypertensive subjects. METHODS: The study population consisted of 108 nondiabetic male patients with newly diagnosed untreated stage I to II essential hypertension (aged 44.6 years, office blood pressure [BP] 148/95 mm Hg). According to ACR values determined as the average of two nonconsecutive overnight spot urine samples, subjects were divided into microalbuminurics (n = 28) (mean ACR = 30 to 300 mg/g) and normoalbuminurics (n = 80) (mean ACR <30 mg/g). RESULTS: Although microalbuminurics as compared to normoalbuminuric hypertensives had greater hs-CRP levels (2.55 +/- 1.18 v 1.45 +/- 0.52 mg/L, P < .0001), independently of confounding factors, these two groups did not differ regarding IL-18 and sCD40L values (P = not significant [NS] for both cases). In the entire population, ACR exhibited a positive correlation with hs-CRP (r = 0.623, P < .0001), whereas there was no association with both IL-18 and sCD40L (P = NS for both cases). When multiple linear regression analysis was performed, it was revealed that age, body mass index, office systolic BP, total cholesterol, and hs-CRP levels were significant independent predictors of the ACR (P < .05). CONCLUSIONS: In essential hypertensive subjects, MA is accompanied by elevated hs-CRP levels, but not by augmented IL-18 and sCD40L concentrations, suggesting activation of different inflammatory pathways in the progression of renal and cardiovascular atherosclerotic disease. The pathophysiologic mechanisms of these associations remain to be further elucidated in future studies.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.