Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.

BACKGROUND: Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized. METHODS: Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis. RESULTS: In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months). CONCLUSIONS: PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.

ATP8B1, ABCB11, and ABCB4 Genes Defects: Novel Mutations Associated with Cholestasis with Different Phenotypes and Outcomes.

OBJECTIVES: To characterize the clinical, laboratory, histologic, molecular features, and outcome of gene-confirmed progressive familial intrahepatic cholestasis (PFIC) 1-3 among Arabs and to evaluate for "genotype-phenotype" correlations. STUDY DESIGN: We retrospectively reviewed charts of 65 children (ATP8B1 defect = 5, ABCB11 = 35, ABCB4 = 25) who presented between 2008 and 2019 with cholestasis. The clinical phenotype of a disease was categorized based on response of cholestasis and itching to ursodeoxycholic acid and ultimate outcome, into mild (complete response), intermediate (partial response, nonprogressive), and severe (progression to end-stage liver disease). RESULTS: Overall, 27 different mutations were identified (ATP8B1, n = 5; ABCB11, n = 11; ABCB4, n = 11), comprising 10 novel ones. Six patients with heterozygous missense mutations (ATP8B1, n = 2; ABCB11, n = 4) had transient cholestasis. Of the remaining 3 patients with PFIC1, 2 developed severe phenotype (splicing and frameshift mutations). Of the remaining 31 patients with PFIC2, 25 developed severe disease (15 due to frameshift and splicing mutations). Of 25 patients with PFIC3, 10 developed a severe phenotype (1 splicing and 3 frameshift mutations; 6 missense). Patients with PFIC2 had significantly shorter survival time and more rapid disease progression than patients with PFIC3 (P < .001). Patients with frameshift mutations in ABCB11 gene (p.Thr127Hisfs∗6) and ABCB4 gene (p.Phe210Serfs∗5) had significantly shorter survival time than missense mutations (P = .011; P = .0039, respectively). CONCLUSIONS: We identified genotype-phenotype correlations among mutations in ABCB11 and ABCB4 genes, which underscore the prognostic value of early genetic diagnosis. The disease course in patients with PFIC3 could be favorably modified by ursodeoxycholic acid therapy.

ADIPSIC DIABETES INSIPIDUS AFTER SECOND RESECTION OF A HYPOTHAMIC ASTROCYTOMA.

OBJECTIVE: We report a case of adipsic diabetes insipidus (ADI) post-astrocytoma resection. METHODS: Clinical and laboratory data are presented. RESULTS: A 16-year-old female with a history of incompletely resected hypothalamic astrocytoma was admitted with a headache. Head magnetic resonance imaging showed an interval increase in a suprasellar lesion with extension to the third ventricle. Following a second stage resection, she developed an increased urine output with diluted urine resulting in a negative fluid balance; however, she was unable to sense thirst. Blood tests showed a serum sodium of 155 mEq/dL (normal, 136 to 145 mEq/dL), serum osmolality at 321 mOs/kg (normal, 285 to 295 mOs/kg) and a urine osmolality of 128 mOsm/kg (normal, 300 to 1,600 mOsm/kg). Serum creatinine and potassium were normal. Pituitary hormone profiles were found to be normal: growth hormone 0.171 ng/mL (normal, 0.123 to 8.05 ng/mL), luteinizing hormone 3.44 mIU/mL (normal, 7.59 to 89.08 mIU/mL), follicle-stimulating hormone 5.60 mIU/mL (normal, 2.55 to 16.69 mIU/mL), thyroid-stimulating hormone 2.9 mIU/mL (normal, 0.35 to 4.94 mIU/mL), free thyroxine 0.92 ng/dL (normal, 0.7 to 1.48 ng/dL), adrenocorticotropic hormone 19.56 pg/mL (normal, 7.2 to 63.3 pg/mL), and prolactin 7.25 ng/mL (normal, 5.18 to 26.53 ng/mL). The patient was treated with desmopressin acetate 120 µg tablets twice daily with a fixed fluid intake of 1.5 to 2.0 L/day with close monitoring of fluid intake, output, and body weight. The response was good with a gradual reduction of serum sodium level of around 7 to 9 mEq/L/day. CONCLUSION: ADI is a rare entity of central diabetes insipidus, where the absence of polydipsia can be challenging in diagnosing and managing the condition. Cases of ADI are likely under reported and clinicians need to be aware of this condition.

Portal Vein Thrombosis in a Patient with Type 1 Diabetes Presenting as Acute Pyelonephritis.

BACKGROUND: Few cases have been reported with respect to portal vein thrombosis in non-cirrhotic patients. Asymptomatic or non-specific symptoms of portal vein thrombosis may lead to misdiagnosis or may delay the diagnosis until complications develop. We report a case of portal vein thrombosis in a patient with type 1 diabetes presenting as acute pyelonephritis. CASE DESCRIPTION: An 18-year-old female with type 1 diabetes on an insulin pump presented with epigastric abdominal pain for 3 days associated with nausea and vomiting. She was a conscious, alert, young female who appeared to be in pain. Vital signs were stable with a random blood sugar (RBS) level of 179 mg/dl. Abdominal examination revealed a soft and lax abdomen with tenderness in the epigastric area and right renal angle, as well as no sign of rigidity or rebound tenderness. No signs of ascites, splenomegaly or hepatomegaly were noted. Investigations showed a WBC count of 10.2, neutrophils at 65%, urine microsopy analysis revealed WBCs between 30-50 per high power field, with culture showing >105 CFU/ml. All parameters of a thrombophilic screen were within normal values. Computed tomography (CT) revealed reduced enhancement of the right kidney, likely indicating acute pyelonephritis, and left portal vein oedema with complete occlusion. Local factors and prothrombotic disorders were ruled out. The patient was managed with ciprofloxacin, enoxaparin and warfarin. Follow-up imaging revealed complete resolution of thrombosis. CONCLUSIONS: Portal vein thrombosis is an uncommon condition in the absence of liver disease. Few case reports exhibit sepsis and portal vein thrombosis. Sepsis can create a predisposed environment for hypercoagulability. To our knowledge, this is the first case report of pyelonephritis with portal vein thrombosis. LEARNING POINTS: Until now, no cases have linked acute pyelonephritis to portal vein thrombosis.Suspect the presence of portal vein thrombosis in a diabetic patient presenting with unusual abdominal pain.Complete revascularization occurs with early treatment.

Knowledge and willingness of physicians about deprescribing among older patients: a qualitative study.

PURPOSE: This study aimed to explore the physician's knowledge and identify the perceived barriers that prevent family medicine physicians from engaging in deprescribing among older patients. METHODS: This qualitative study was designed and conducted using an interpretive theoretical approach. Purposive sampling was undertaken, whereby family medicine physicians of King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia, were invited to participate in the study. The topic guidelines were designed to give the physicians the freedom to express their views on exploring their knowledge about deprescribing and to identify the perceived barriers and enablers that prevent them from engaging in the practice in older patients. The focus group discussions were conducted in English, audio-taped with permission, and transcribed verbatim. Each transcript was independently reviewed and coded separately to explore the themes and sub-themes. RESULTS: A total of 15 physicians participated in three focus group discussions. Their thematic content analysis identified 24 factors that facilitated or hindered deprescribing. The facilitators included cost-effectiveness and time effectiveness, side effects avoidance, clinical pharmacist's role, need for system(s) to help in applying deprescribing, and patient counseling/education. Similarly, barriers included lack of knowing the deprescribing term and process, patient comorbidities, risk/fear of conflict between physicians and clinical pharmacists, lack of documentation and communication, lack of time or crowded clinics, and patient resistance/acceptance. CONCLUSION: The study identified several factors affecting family medicine physician's deprescribing behavior. The use of theoretical underpinning design helped to provide a comprehensive range of factors that can be directed when defining targets for intervention(s).