Specimen oriented intraoperative margin assessment in oral cavity and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Evaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective case series and subsequent prospective cohort study SETTING: Tertiary care academic teaching hospital SUBJECTS AND METHODS: Retrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 - December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 - December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost. RESULTS: Analysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD. CONCLUSION: Implementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.

The role of scientific evidence in decisions to adopt complex innovations in cancer care settings: a multiple case study in Nova Scotia, Canada.

BACKGROUND: Health care delivery and outcomes can be improved by using innovations (i.e., new ideas, technologies, and practices) supported by scientific evidence. However, scientific evidence may not be the foremost factor in adoption decisions and is rarely sufficient. The objective of this study was to examine the role of scientific evidence in decisions to adopt complex innovations in cancer care. METHODS: Using an explanatory, multiple case study design, we examined the adoption of complex innovations in five purposively sampled cases in Nova Scotia, Canada. Data were collected via documents and key informant interviews. Data analysis involved an in-depth analysis of each case, followed by a cross-case analysis to develop theoretically informed, generalizable knowledge on the role of scientific evidence in innovation adoption that may be applied to similar settings and contexts. RESULTS: The analyses identified key concepts alongside important caveats and considerations. Key concepts were (1) scientific evidence underpinned the adoption process, (2) evidence from multiple sources informed decision-making, (3) decision-makers considered three key issues when making decisions, and (4) champions were essential to eventual adoption. Caveats and considerations related to the presence of urgent problems and short-term financial pressures and minimizing risk. CONCLUSIONS: The findings revealed the different types of issues decision-makers consider while making these decisions and why different sources of evidence are needed in these processes. Future research should examine how different types of evidence are legitimized and why some types are prioritized over others.

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens.

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy.

Tandem mass spectrometry (MS/MS) was used to analyze multiple serum metabolites for the first time in a surfactant/virus mouse model of acute hepatic encephalopathy (AHE). AHE is characterized by acute liver failure that can lead to potentially lethal increases in intracranial pressure. We have reproduced AHE in young CD-1 mice exposed from postnatal day (P) 2-13 to the industrial surfactant, Toximul 3409F (Tox), and then infected intranasally on P14 with sublethal doses (LD(10-30)) of mouse-adapted human influenza B (Lee) virus (FluB). The sera analyzed by MS/MS were from mice exhibiting typical markers of Tox-mediated potentiation of viral illness, including reduced weights and blood glucose levels. Most metabolite abnormalities were not evident until five days after viral infection (P19), the time corresponding to the onset of weight loss and mortality. Values for fatty acylcarnitines and amino acids in the Tox+FluB-treated mice were either additive or supra-additive relative to the effects of either treatment alone. Amino acid profiles were consistent with those reported for human AHE. None of the treated mice exhibited signs of carnitine deficiency, and propionylcarnitine levels were normal. On P19, mice given combined Tox+FluB treatment had significant increases in levels of both medium- and long-chain acylcarnitines (C6:0-C12:0 and C14:0-C20:0, respectively), including their monounsaturated metabolites. Levels of medium-chain dicarboxylic and long-chain hydroxy-acylcarnitines were also elevated in the combined treatment group. The results of this study indicate a diffuse mitochondrial dysfunction in Tox+FluB-treated mice that results in a serum metabolite profile unique from those observed in classic inherited metabolic disorders.

BK virus nephropathy in a heart transplant recipient: case report and review of the literature.

The human polyomavirus BK virus (BKV) remains latent in the urinary tract and may be reactivated in immunocompromised states. BKV is noted to be the etiologic agent of polyomavirus-associated nephropathy (PVAN), which is a significant cause of allograft failure in renal transplant patients. Renal dysfunction following non-renal solid organ transplantation is common and is typically attributed to drug toxicity or patient comorbidities. In this article we describe a case of PVAN in the native kidneys of a heart transplant recipient and review the literature. Although this is only the fourth case reported, BKV nephropathy should be considered in the differential diagnosis of new renal failure following non-kidney solid organ transplantation, as early diagnosis of PVAN is necessary to prevent irreversible renal damage.

Sustained remission of lupus nephritis.

The aim of this study was to describe the clinical course of patients with lupus nephritis (LN) who attain a sustained remission (SR) and identify predictors of SR. A retrospective study of patients with biopsy-proven LN were followed for up to 10 years. SR was defined as normal renal function, urine protein <0.5g/day, and an inactive urine sediment without significant immunosuppressive maintenance therapy for no less than three years. Control patients had LN but did not fulfill the criteria for SR. Data was collected at diagnosis of LN (T0), at onset of remission (T1), and at final follow-up (T2). A total of 35 patients were identified, 16 with a SR of LN and 19 controls, with a mean +/- SD follow-up of 126.4 +/- 8.5 months. Remission of LN was achieved following 37.7 +/- 6.8 months of therapy. At diagnosis (T0) the WHO classification of nephritis, activity and chronicity scores of renal biopsies were comparable in the two groups. At final follow-up (T2), the mean estimated creatinine clearance for the SR group was significantly higher than in controls (P = 0.009) and disease activity (SLEDAI scores) was lower (P = 0.002). Cumulative damage (SDI scores) in the SR group did not increase after patients entered remission (P = 0.250), whereas the mean SDI score in the control group increased significantly (P = 0.014) even when renal variables were excluded (P = 0.016). Multivariate analysis revealed that female gender (P = 0.023), older age (P = 0.034), higher nonrenal SLEDAI scores (P = 0.016) at the time of diagnosis of LN and absence of azathioprine (P = 0.010) were predictive of SR. It was concluded that remission of LN occurs in a substantial proportion of systemic lupus erythematosus (SLE) patients and may be sustained without maintenance immunosuppressive therapy. It is associated with a significantly slower accrual of both renal and non-renal damage over the ensuing seven years.

Histologic examination of "fascia" used in colporrhaphy.

OBJECTIVE: To perform a histologic examination of tissue identified as fascia and used during colporrhaphy. METHODS: In patients undergoing primary anterior and posterior colporrhaphy, biopsies were taken from three surgically distinct vaginal tissues types: the wall, the "fascia," and areolar tissue. The biopsies were placed in formalin, identified numerically, and sent to pathology for staining with hematoxylin-eosin, Masson trichrome for collagen, Movat for elastin, and immunoperoxidase stain for actin in smooth muscle. Simultaneous photographs were taken of the biopsy sites. The histologic diagnosis was compared with the surgical diagnosis. RESULTS: A total of 60 samples were taken from five women. The specimens from two of these patients were disqualified. The pathologist made the following histologic diagnosis for each type of surgical specimen: vaginal wall, mucosa and underlying connective tissue; fascia, moderately dense connective tissue with smooth muscle; areolar tissue, loose connective tissue. The histologic appearance of the "fascia" was indistinguishable from the deeper aspects of the vaginal wall. It was composed of the same proportions of smooth muscle, elastin, and collagen. Using the histologic appearance as the "gold standard," the accuracy of the surgical diagnosis was: "vaginal wall," 12 of 12 (100%); "fascia," seven of 12 (58%); and "areolar tissue," eight of 12 (67%). CONCLUSIONS: The surgical "fascia" used during colporrhaphy consists of moderately dense connective tissue with smooth muscle similar to the deep aspects of the vaginal wall, is the same in both the anterior and posterior compartments, and is an artifact of the surgical dissection used to separate the vaginal wall from the underlying organs.

A combination of abnormal immunoarchitecture and reproducible clonal bands identifies the biologic nature of cutaneous B-cell infiltrates.

In the multiparametric evaluation of cutaneous B-cell infiltrates (CBIs), immunoarchitectural features have been underused, and B-cell clonality alone has limited clinical usefulness. Our aim was to assess the usefulness of immunoarchitectural abnormalities (IAs) and clonality in the diagnosis of CBIs. On 39 CBIs, immunohistochemistry was performed using anti-CD45, anti-CD45RO, anti-CD3, anti-CD20, anti-CD21, and anti-CD35, and polymerase chain reaction was used to detect immunoglobulin heavy chain rearrangement. There were 33 cutaneous lymphoid hyperplasias (CLHs) and 6 cutaneous B-cell lymphomas. IAs were present in 9 lesions and clonal bands in 14 lesions. In 6 cutaneous B-cell lymphomas, IAs were associated with pure and reproducible clonal bands. IAs in 3 CLH lesions with a superficial infiltrate were not associated with clonal bands. Clonal bands in 8 CLH lesions without IAs were not reproducible from deeper sections; furthermore, in 5 of 8 cases, these were present against a background smear. A combination of IAs and clonality is a useful adjunct in the diagnosis of CBIs.

Mycosis fungoides and cutaneous Hodgkin's disease in the same patient: a case report.

We describe a case of a 34-year-old man who presented with a 10-year history of mycosis fungoides and recent onset of inguinal lymphadenopathy, fever, and cutaneous nodules on the right hip. Biopsy of the inguinal lymph node showed mixed cellularity Hodgkin's lymphoma. Biopsy of the pre-existing skin lesions showed mycosis fungoides, while that of the nodules on the hip revealed cutaneous Hodgkin's lymphoma. Immunohistochemical and molecular analysis demonstrated a null phenotype in the Reed-Sternberg cells of the Hodgkin's disease lesions, and a T-cell phenotype in the lymphoid cells of the mycosis fungoides lesions. He was treated with chemotherapy for Hodgkin's disease, which is in remission 11 years later. Topical nitrogen mustard and maintenance PUVA therapy have been used for the mycosis fungoides, which is also in remission.