Development of a Scoring Rubric Assessing Medical Students' Explanations of Pathology Reports.

CONTEXT.­: With increasing availability of immediate patient access to pathology reports, it is imperative that all physicians be equipped to discuss pathology reports with their patients. No validated measures exist to assess how pathology report findings are communicated during patient encounters. OBJECTIVE.­: To pilot a scoring rubric evaluating medical students' communication of pathology reports to standardized patients. DESIGN.­: The rubric was iteratively developed using the Pathology Competencies for Medical Education and Accreditation Council for Graduate Medical Education pathology residency milestones. After a brief training, third- and fourth-year medical students completed 2 standardized patient encounters, presenting simulated benign and malignant pathology reports. Encounters were video recorded and scored by 2 pathologists to calculate overall and item-specific interrater reliability. RESULTS.­: All students recognized the need for pathology report teaching, which was lacking in their medical curriculum. Interrater agreement was high for malignant report scores (intraclass correlation coefficient, 0.65) but negligible for benign reports (intraclass correlation coefficient, 0). On malignant reports, most items demonstrated good interrater agreement, except for discussing the block (cassette) summary, explaining the purpose of the pathology report, and acknowledging uncertainty. Participating students (N = 9) felt the training was valuable given their limited prior exposure to pathology reports. CONCLUSIONS.­: This pilot study demonstrates the feasibility of using a structured rubric to assess the communication of pathology reports to patients. Our findings also provide a scalable example of training on pathology report communication, which can be incorporated in the undergraduate medical curriculum to equip more physicians to facilitate patients' understanding of their pathology reports.

Standard-Volume Is As Effective As High-Volume Plasma Exchange for Patients With Acute Liver Failure.

Background/Aims: Acute liver failure (ALF) is associated with fatal outcomes without liver transplantation. Two randomized studies reported standard volume (SV) and high volume (HV) plasma exchange (PLEX) as effective therapeutic modalities for patients with ALF. However, no studies have compared the safety and efficacy of SV with HV PLEX, which we aimed to assess. Methods: This retrospective study included patients with ALF admitted between March 2021 and March 2023 who underwent PLEX. All patients underwent HV PLEX until May 2022, and then thereafter, SV PLEX was performed. The objectives of the study were to compare transplant-free survival (TFS) at 30 days, efficacy in reducing severity scores, biochemical variables, and adverse events between SV (total plasma volume x 1) and HV (total plasma volume x 1.5-2) PLEX. Results: Forty two ALF patients (median age: 23.5 years; females: 57.1%; MELD Na: 34.67 ± 6.07; SOFA score- 5.24 ± 1.42) underwent PLEX. Of these, 22 patients underwent SV-PLEX, and 20 underwent HV-PLEX. The mean age, sex, etiology distribution, and severity scores were similar between the groups. The median number of PLEX sessions (2) was similar in both groups. On Kaplan-Meier analysis, TFS was 45.5% in SV group and 45% in HV group (P = 0.76). A comparable decline in total bilirubin, PT/INR, ammonia, and MELD Na scores was noted in both groups. The cumulative number of adverse events was similar between the HV group (77.3%) and SV group (54.5%; P = 0.12). Conclusions: SV PLEX is safe and as effective as HV PLEX in patients with ALF. Further randomized controlled trials with a larger sample size are needed to validate these findings.

Longevity after radiotherapy of stage III lung cancer: superior vena cava obstruction is associated with early mortality.

BACKGROUND: People with locally advanced lung cancer have a poor prognosis. Physicians are unable to accurately predict life expectancy of patients. The aims of this retrospective study were to identify the life spans of individuals after radiotherapy of stage III carcinoma of the lung and to determine whether potential prognostic factors could identify people with distinct life spans. METHODS: Between September 1981 and August 2010, 133 consecutive individuals underwent definitive or palliative radiotherapy (with or without chemotherapy) for stage IIIA/IIIB disease. Analysis of the survival data revealed that 14 patients experienced long-term survival, exceeding 36 months; 94 patients had a short-term life span (STLS), extending between 4 and 36 months, and 25 patients were in the end-of-life (EOL) period, referring to the last 3 months of life. Recognized pre-treatment clinicopathological features were tested for their impact on prognosis. RESULTS: The largest proportion of patients presenting with superior vena cava obstruction (SVCO) (P<0.001) and receiving palliative radiotherapy (P=0.009) were from the EOL group. Most of the individuals with inadequate or no health insurance belonged to the STLS and EOL cohorts (P=0.001). Multivariate analysis revealed that the presence of SVCO was an independent factor predictive of shortened survival/EOL status (P=0.001). CONCLUSIONS: Our study showed that a particular disease characteristic, health insurance status and provision of contemporary therapy can influence individual longevity. Selection and prioritization of health care resources remain important; therefore, identification of influential prognostic factors in lung cancer patients deserves further scrutiny.

Nicotinamide Phosphoribosyl Transferase a Reliable Marker of Progression in Cervical Dysplasia.

BACKGROUND/AIM: Nicotinamide phosphoribosyl transferase (Nampt) catalyses the rate-limiting step of the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway. Nampt is highly expressed in several epithelial and mesenchymal neoplasms, where is promotes cell-cycle progression ans chemotherapy resistance. To our knowledge, alterations in Nampt expression have not been examined in cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed immunohistochemical analysis for Nampt using tissue microarrays on 14 samples of benign cervical squamous epithelium and 15 CIN I, 15 CIN II, and 13 samples of CIN III. The SCCs included 5 low-grade, 67 intermediate-grade, and 81 high-grade tumors. RESULTS: Nampt levels increased with increased CIN grades were compared to benign cervical squamous epithelium. Similarly, Nampt levels increased with increasing SCC grade. CONCLUSION: Nampt expression is a reliable marker of progression in cervical dysplasia and SCC.

Long-term Survival After Stereotactic Radiosurgery of Brain Metastases: A Case Series with 10-year Follow-up.

Patients with brain metastases (BRM) generally have a poor prognosis with infrequent long-term outcomes. Four patients treated by stereotactic radiosurgery (SRS) for BRM between 2000 and 2010 with a minimum follow-up of 10 years are described. The mean age was 43.5 years, and these individuals exhibited good performance status at the time of diagnosis of intracranial disease. BRM was solitary or multiple, and the primary malignant tumor originated from the thyroid gland, lung, mediastinum or large intestine. Progression of the original and secondary tumors subsequent to diagnosis and SRS was not observed. Radioimaging of the brain obtained 9 years later in one of the patients who was asymptomatic at follow-up revealed white matter changes; BRM in this individual was treated by tumor resection and cranial irradiation prior to SRS. We contend that extended longevity is not precluded when standard management of BRM is practiced in selected cases.

Contribution of human smooth muscle cells to amyloid angiopathy in AL (light-chain) amyloidosis.

OBJECTIVE: Amyloid light-chain (AL) amyloidosis is a disease process that often compromises the peripheral vascular system and leads to systemic end-organ dysfunction. Although amyloid formation in vessel walls is a multifaceted process, the assembly of the native light chains (LCs) into amyloid fibrils is central to its pathogenesis. Recent evidence suggests that endocytosis and endolysosomal processing of immunoglobin LCs by host cells is essential to the formation of amyloid fibrils that are deposited in at least some tissues. The aim of this study was to elucidate the role of vascular smooth muscle in amyloid angiopathy. METHODS: Human coronary artery smooth muscle cells (SMCs) were grown on coverslips, four chamber glass slides, and growth factor-reduced Matrigel matrix in the presence of 10 µg/ml of ALs (λ and κ isotypes), nonamyloidogenic LCs, and culture medium (negative control) for 48 and 72 hours. Thereafter, a detailed light microscopic, immunohistochemical, and ultrastructural evaluation was conducted to verify amyloid deposition and characterize the role of SMCs in the formation of amyloid deposits in the various experimental conditions. RESULTS: Amyloid deposits were detected extracellulary as early as 48 hours after exposure of vascular smooth muscle cells (VSMCs) to AL-LCs (amyloidogenic light chains) as confirmed by affinity to Congo red dye, thioflavin T fluorescence, and transmission electron microscopy. No amyloid was present in the cultures of SMCs treated with medium alone or nonamyloidogenic LCs. SMCs associated with amyloid deposits exhibited CD68, lysosome-associated membrane protein 1-1, and intracellular lambda light chain expression and only focal smooth muscle actin and muscle-specific actin positivity. Electron microscopy revealed these cells to have an expanded mature lysosomal compartment closely associated with deposits of newly formed amyloid fibrils. CONCLUSIONS: The interaction of amyloidogenic LCs with VSMCs is necessary for the formation of amyloid fibrils that are deposited in peripheral vessels. VSMCs participate in the formation of amyloid by the intracellular processing of AL-LCs, which is possible due to their transformation from a smooth muscle to a macrophage phenotype. The formation of amyloid fibrils occurs in the mature lysosomal compartment of transformed cells. The amyloid that is formed is then extruded into the extracellular matrix.

Ten-year Survivors After Contemporary Management of Advanced 'Horseshoe' Anterior Commissure Laryngeal Cancer.

BACKGROUND: Combinations of treatment modalities for locally extensive carcinomas of the larynx constitute the standard of care. Advanced 'horseshoe' anterior commissure laryngeal cancer (HACLC) is a disease entity that has not received much attention in the literature. The aims of this study were to evaluate prolonged survival in patients after standard combined therapy for HACLC and to identify clinicopathological factors influential towards an extended outcome. PATIENTS AND METHODS: Fourteen patients (10-year survivors) with stage III or IV laryngeal cancer involving the anterior commissure and both true vocal cords were treated with total laryngectomy (and postoperative radiotherapy in 11 individuals). RESULTS: During follow-up, ranging from 123 to 256 months, locoregional recurrent disease and distant metastasis were not observed. Complications after therapy were manageable and few. The long-term survivors were particularly difficult to characterize. CONCLUSION: The optimal treatment for advanced HACLC has not been clarified; however, in this study, total laryngectomy and the indicated use of postoperative radiotherapy, were successful in achieving long-term disease-free survival. Predictive factors for longevity were not detected in this limited experience.

ABSOLUTE PLATELET REFRACTORINESS ASSOCIATED WITH HLA ANTIBODIES: A CASE REPORT.

Refractoriness to platelet transfusion is a complex process that can be due to a diverse array of etiologies. We report a case of refractoriness in a patient with acute myelogenous leukemia (AML) and the diagnostic challenge associated with it. During the course of myeloablative therapy the patient demonstrated no response to multiple sequential platelet transfusions given to prevent the onset of bleeding complications in the setting of severe thrombocytopenia. Diagnostic evaluation revealed multiple potential underlying etiologies and contributing factors, with alloimmunity to HLA antigens determined to be the most probable cause after thorough laboratory investigation.

Increased Nicotinamide Phosphoribosyltransferase in Rhabdomyosarcomas and Leiomyosarcomas Compared to Skeletal and Smooth Muscle Tissue.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in NAD synthesis and is up-regulated in several human malignancies, including breast, colon, prostate, thyroid, gastric, and several hematopoietic malignancies. In some malignancies, such as gastric, thyroid, and prostate carcinomas, higher NAMPT expression correlates with deeper tumor invasion, increased metastatic potential and chemotherapy resistance. We employed tissue microarray immunohistochemistry to examine NAMPT expression in benign skeletal and smooth muscle, leiomyomas, leiomyosarcomas (graded low-, intermediate-, and high-grade), and spindle, embryonal, pleomorphic, and alveolar rhabdomyosarcomas. We found low to intermediate NAMPT expression in benign tissue, leiomyomas, leiomyosarcomas (low- and intermediate-grades), and spindle cell rhabdomyosarcomas. In contrast, high-grade leiomyosarcomas and embryonal, alveolar, and pleomorphic rhabdomyosarcomas showed high NAMPT expression. Herein we show for the first time that NAMPT is overexpressed in certain sarcoma types and the level of NAMPT expression correlates with tumor behavior.

Neuroendocrine tumors in the ovary: histogenesis, pathologic differentiation, and clinical presentation.

OBJECTIVE: Primary neuroendocrine tumors in the ovary are rare. These tumors arise from the neuroendocrine cell system of ovarian stroma and surface epithelium, and may also arise from teratoma. We present four primary ovarian neuroendocrine tumors and compare clinicopathologic findings based on tumor histogenesis and site of origin. DESIGN: Four primary ovarian neuroendocrine tumors were identified from our 10-year departmental archives. H&E slides and immunostains were reviewed and the diagnoses were confirmed. Clinical history, imaging studies, and follow-up data were obtained from medical records. RESULTS: Patients' ages ranged from 26 to 63. All patients presented with abdominal discomfort and unilateral or bilateral ovarian masses. MRI and CT scans from cases 1 and 2 revealed a solid ovarian mass with no extra-ovarian extension. In case 1, the patient also had a cystic mass in the opposite ovary and an elevated urine 5-HIAA. Microscopically, case 1 revealed a well-differentiated carcinoid tumor with no surface epithelial involvement, and a mature teratoma in the contralateral ovary. Case 2 revealed a stromal carcinoid within the ovarian parenchyma. Imaging studies from cases 3 and 4 showed large complex masses with peritoneal implants and ascites. In both cases 3 and 4, tumor grossly involved both ovarian parenchyma and surface epithelium with multiple pelvic implants. In addition, liver metastases were present in case 4. Microscopically, these tumors were poorly differentiated carcinoma with neuroendocrine differentiation. Histologic sections revealed extensive necrosis, and both cases showed positivity for neuroendocrine markers. CONCLUSIONS: Primary neuroendocrine tumors in the ovary are rare and consist of a group of heterogeneous malignancies that express similar immunohistochemical markers. Primary neuroendocrine tumors that are limited to the ovarian parenchyma often arise from ovarian stroma and teratoma, and are carcinoid tumors with a good prognosis. Neuroendocrine tumors that arise from surface epithelium or dedifferentiate from de novo carcinoma often involve both ovarian stroma and surface epithelium and clinically present as aggressive malignancies with poor prognoses.

ALK-rearrangements and testing methods in non-small cell lung cancer: a review.

The anaplastic lymphoma tyrosine kinase (ALK) gene was first described as a driver mutation in anaplastic non-Hodgkin's lymphoma. Dysregulated ALK expression is now an identified driver mutation in nearly twenty different human malignancies, including 4-9% of non-small cell lung cancers (NSCLC). The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities. Here we review ALKmediated signal transduction pathways and compare the molecular protocols used to identify dysregulated ALK expression in NSCLC. We also discuss the use of crizotinib and second generation ALK tyrosine kinase inhibitors in the treatment of ALK positive NSCLC, and the known mechanisms of crizotinib resistance in NSCLC.