Primary Thyroid Lymphoma: How Molecular Biology and Ancillary Techniques Can Help the Cytopathologist Overcome This Diagnostic Challenge.

Primary thyroid lymphoma (PTL) occurs rarely, its diagnosis is a challenge, and the prognosis of these patients depends on the time of diagnosis. Even though fine-needle aspiration cytology (FNAC) is recognized as the most accurate tool for detecting thyroid malignancies, its sensitivity for PTL is poor. Both clinical and ultrasound presentation of PTL can be atypical, and laboratory tests fail to furnish relevant data. Consequently, the reliability of a cytopathologist facing PTL can be poor, even when he is aware of its clinical information. In addition, the cases described in the literature are extremely rare and fragmentary, and consequently, the molecular data currently available for this neoplasm are practically negligible. Here, we present a case report in order to discuss the intrinsic limitations in achieving a final diagnosis of PTL and how using molecular diagnostics to identify potential mutational models can improve the evaluation of this neoplasm.

Angiotensin System Polymorphisms' in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study.

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS), a metabolic cascade regulating pressure and circulating blood volume, has been considered the main system involved in the pathogenesis of severe lung injury and organs decline in COVID-19 patients. The angiotensin I-converting enzyme (ACE1), angiotensin-converting enzyme 2 (ACE2), angiotensinogen (AGT) and receptors angiotensin II receptor type 1 (AGTR1) are key factors for SARS-CoV-2 entering in the cells, sodium and water retention with an increase blood pressure, promotion of fibrotic and inflammatory phenomena resulting in a cytokine storm. METHODS: In this pilot study, the frequencies of six polymorphisms in the ACE1, ACE2, AGT and AGTR1 genes were analysed in symptomatic patients affected by COVID-19 and compared with the results obtained from asymptomatic subjects. RESULTS: Thus, we have identified that rs2074192 (ACE2), rs1799752 (ACE1) and rs699 (AGT) SNPs could potentially be a valuable tool for predicting the clinical outcome of SARS-CoV-2 infected patients. A genetic predisposition may be prospected for severe internal organ damages and poor prognosis in patients with COVID-19 disease, as observed in symptomatic vs asymptomatic. CONCLUSION: This study provides evidence that analysis of RAAS polymorphisms could be considered the key point in understanding and predicting the SARS-CoV-2 course infection.

Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease.

The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.

Dysbiosis in intestinal microbiome linked to fecal blood determined by direct hybridization.

The important physiological and pathophysiological roles of intestinal human microbiome (HMB) in human health have been emerging, owing to the access to molecular biology techniques. Herein we evaluated, for the first time, the intestinal HMB through direct hybridization approach using n-counter flex DX technology which bypasses the amplification procedure currently applied by other technologies to study the human microbiome. To this purpose, a clinical study was carried out on fecal samples, recruiting both healthy volunteers (N-FOB) and subjects positive for occult blood (P-FOB). A relevant custom panel of 79 16S rRNA target gene was engineered and 32 of them displayed a variation between the two clusters of subjects. Our findings revealed that bacteria belonging to Proteobacteria have higher distribution in P-FOB describing dysbiosis. Similarly, Bacteroidetes and Firmicutes phylum display high distribution in P-FOB. Of interest, the presence of Clostridium difficile that belongs to Firmicutes phylum displayed about 70% of low presence in N-FOB compared to P-FOB subjects. Only one bacterium belonging to the Actinobacteria phylum, the Bifidobacterium bifidum, was present.

KRAS and BRAF Concomitant Mutations in a Patient with Metastatic Colon Adenocarcinoma: An Interesting Case Report.

A 68-year-old female patient with tenesmus and blood in the stool was admitted to the S.G. Moscati Hospital of Taranto. Investigations revealed infiltrative mucinous colon adenocarcinoma accompanied by lymph node metastases. Following surgery and adjuvant chemotherapy, computed tomography (CT) and carcinoembryonic antigen screening were negative. Two years later, CT demonstrated a liver lesion. Histologic and genetic analyses confirmed the diagnosis of metastatic colorectal cancer with the coexistence of KRAS and BRAF mutations in hepatic metastases and the presence of the BRAF V600E in the primary tumour. It is unclear whether the lack of response was due to BRAF mutations, but the data suggest that mutated BRAF confers resistance to anti-epidermal growth factor receptor therapy. In our patient, BRAF mutation turned out to be a negative prognostic factor, and it may have been the cause of clinical implications for disease progression and therapeutic responses.

Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism.

Importance: In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects. Objective: To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism. Design, Setting, and Participants: A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded. Main Outcomes and Measures: Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery. Results: On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater. Conclusions and Relevance: In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

Retroperitoneoscopic adrenalectomy: tips and tricks.

Posterior retroperitoneoscopic adrenalectomy has recently increased in popularity and currently adopted in about 20% of referral centers. It may provide more direct access to the adrenals, thus avoiding post-operative adhesions and the need for patient repositioning in bilateral adrenalectomy. Although it has been suggested to be feasible for large tumors, large tumor size is indicated as the main limitation of PRA, mainly because of the small space available for dissection.

Outcome of adrenalectomy for subclinical hypercortisolism and Cushing syndrome.

BACKGROUND: We compared operative and metabolic outcomes in patients with subclinical Cushing syndrome and Cushing syndrome caused by unilateral adrenal lesion, aiming to clarify the role of glucocorticoid replacement treatment in patients with subclinical Cushing syndrome after adrenalectomy. METHODS: The medical records of all the patients who underwent unilateral adrenalectomy for subclinical Cushing syndrome or Cushing syndrome were reviewed. Diagnostic criteria for subclinical Cushing syndrome were a pathologic dexamethasone suppression test plus 2 additional criteria. RESULTS: Twenty-nine patients with subclinical Cushing syndrome and 50 with Cushing syndrome were identified. No significant difference was found between patients with subclinical Cushing syndrome and Cushing syndrome regarding lesion size, operative time, and hospital stay. Two patients out of 29 with subclinical Cushing syndrome and 3 out of 50 patients with Cushing syndrome experienced Clavien-Dindo grade II complications (P = .87). All the patients required postoperative glucocorticoid replacement that was discontinued within 6 months in 28 of the 29 patients with subclinical Cushing syndrome and in 3 out of 50 Cushing syndrome patients (P < .005). At long-term follow-up, adrenalectomy significantly improved hypertension and diabetes in affected patients, with no differences between subclinical Cushing syndrome and Cushing syndrome. Hypercortisolism was resolved in all the cases. CONCLUSION: Operative and metabolic outcomes of adrenalectomy are similar in subclinical Cushing syndrome and Cushing syndrome. Postoperative glucocorticoid replacement treatment is advisable in all patients with subclinical Cushing syndrome. Prolonged adrenal insufficiency is more frequent in Cushing syndrome patients.

Post-thyroidectomy hypocalcemia is related to parathyroid dysfunction even in patients with normal parathyroid hormone concentrations early after surgery.

BACKGROUND: Hypocalcemia may develop even in the presence of normal postoperative parathyroid hormone (PTH) concentrations. We aimed to identify risk factors of hypocalcemia in patients with normal PTH concentration early after total thyroidectomy (TT). METHODS: We included 1,504 consecutive patients who underwent TT between January 2012 and December 2013. Significant hypocalcemia was defined as serum calcium concentrations of <8.0 mg/dL. RESULTS: Overall, 333 patients had subnormal PTH 4 hours after surgery (4-hour PTH; <10 pg/mL) and received oral calcium (OC) and calcitriol supplementation. Among the 1,171 patients with normal 4-hour PTH (≥ 10 pg/mL; euparathyroid), 211 experienced hypocalcemia and required OC administration. Among the euparathyroid patients, no difference was found between normocalcemic and hypocalcemic patients in terms of age, hormonal status, preoperative PTH, 25-hydroxy vitamin D (25OH-VD), magnesium, and phosphate concentrations. On univariate analysis, euparathyroid hypocalcemic patients were more frequently females, had significantly lower preoperative serum calcium and 4-hour PTH concentrations, and greater decreases in PTH. Independent risk factors for hypocalcemia with normal 4-hour PTH were preoperative serum calcium concentration and PTH decline of ≥ 50%. CONCLUSION: Female sex, toxic goiter, and 25OH-VD deficiency are not risk factors for post-TT hypocalcemia. Relative parathyroid insufficiency seems to be the principal mechanism of post-thyroidectomy hypocalcemia, even in patients with normal postoperative PTH concentrations.

Combining early postoperative parathyroid hormone and serum calcium levels allows for an efficacious selective post-thyroidectomy supplementation treatment.

BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca ≥ 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH ≤ 10 pg/ml), OC 3 g + calcitriol (VD) 1 µg per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (≤10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.

Laparoscopic splenectomy for atraumatic splenic rupture.

A traumatic splenic rupture (ASR) is a rare clinical entity. Several underlying benign and malignant conditions have been described as a leading cause. We report on a case of ASR in a 41-year-old man treated with laparoscopic splenectomy. Considering ASR as a life-threatening condition, a prompt diagnosis can be life saving.