An Autopsy Report of an Adenoid Cystic Carcinoma Arising in the Trachea

Abstract

While adenoid cystic carcinoma is a common malignancy to arise within the salivary glands (21.9%) (Kokemueller et al. in Int J Oral Maxillofac Surg 33:25–31, 2004), it is seldom encountered as a tracheal mass and represents < 1% of all lung cancers. Tracheal tumors are an uncommon cause of dyspnoea due to their relatively rare occurrence (Baydur and Gottlieb in JAMA 234:829–831, 1975). They pose considerable diagnostic challenge clinically as their symptoms mimics more commoner ailments like asthma and chronic bronchitis. As they carry good prognosis, a timely diagnosis is highly warranted for appropriate therapeutic intervention. We describe a rare autopsy case of an adenoid cystic carcinoma in a middle-aged gentleman who presented with severe breathlessness and dyspnoea and succumbed to his illness after a brief hospital stay. Because the symptoms were non-specific, he was treated on lines of asthma and bronchitis.

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Cholangiocarcinoma in a Child with Progressive Abdominal Distension and Secondary Hypercalcemia

Cholangiocarcinoma is extremely rare in childhood and has been reported in association with other underlying diseases. The survival and prognosis are dismal especially in patients with unresectable or advanced stage cholangiocarcinoma. Overall survival in patients with metastatic cholangiocarcinoma could be increased by using combination chemotherapy with cisplatin and gemcitabine. A case of childhood cholangiocarcinoma was hereby reported.

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Diagnostik und Therapie des M. Osler

Zusammenfassung

Der M. Osler stellt eine autosomal-dominante seltene Erberkrankung dar. Die Betroffenen leiden v. a. unter der Epistaxis. Die Diagnosestellung beruht auf den Curaçao-Kriterien und der Gendiagnostik. Organmanifestationen finden sich als arteriovenöse Shunts im Bereich von Lunge, Leber, Gastrointestinaltrakt, seltener im Zentralnervensystem (ZNS) und anderen Körperregionen. Viele Patienten mit gastrointestinalen und anderen Organmanifestationen sind häufig klinisch asymptomatisch. Das Organscreening ist von elementarer Bedeutung zur Vermeidung von Komplikationen und sollte an Zentren mit besonderer Expertise durchgeführt werden. Derzeit existiert keine kausale Therapieoption. Von HNO-ärztlicher Seite stellt die nasale Schleimhautpflege sowie die endonasale Lasertherapie eine wichtige Säule in der Behandlung der Epistaxis dar. Medikamentöse Therapieansätze zielen auf die Kompensation der Haploinsuffizienz sowie Antiangiogenese ab und sind z. T. mit schwerwiegenden Nebenwirkungen assoziiert.

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Radiological differences between HIV-positive and HIV-negative children with cholesteatoma

Publication date: July 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 110
Author(s): J.K. McGuire, J.J. Fagan, M. Wojno, K. Manning, T. Harris
IntroductionHIV-positive children are possibly more prone to developing cholesteatoma. Chronic inflammation of the middle ear cleft may be more common in patients with HIV and this may predispose HIV-positive children to developing cholesteatoma. There are no studies that describe the radiological morphology of the middle ear cleft in HIV-positive compared to HIV-negative children with cholesteatoma.ObjectivesCompare the radiological differences of the middle ear cleft in HIV-positive and HIV-negative children with cholesteatoma.MethodsA retrospective, cross-sectional, observational analytical review of patients with cholesteatoma at our institute over a 6 year period.ResultsForty patients were included in the study, 11 of whom had bilateral cholesteatoma and therefore 51 ears were eligible for our evaluation. HIV-positive patients had smaller (p=0.02) mastoid air cell systems (MACS). Forty percent of HIV-positive patients had sclerotic mastoids, whereas the rate was 3% in HIV-negative ears (p<0.02). Eighty-two percent of the HIV-positive patients had bilateral cholesteatoma compared to 7% of the control group (p<0.02). There was no difference between the 2 groups with regards to opacification of the middle ear cleft, bony erosion of middle ear structures, Eustachian tube obstruction or soft tissue occlusion of the post-nasal space.ConclusionHIV-positive paediatric patients with cholesteatoma are more likely to have smaller, sclerotic mastoids compared to HIV-negative patients. They are significantly more likely to have bilateral cholesteatoma. This may have implications in terms of surveillance of HIV-positive children, as well as, an approach to management, recurrence and follow-up. HIV infection should be flagged as a risk factor for developing cholesteatoma.



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Trends in management of obstructive sleep apnea in pediatric patients with Down syndrome

Publication date: July 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 110
Author(s): Jennifer Best, Sean Mutchnick, Jonathan Ida, Kathleen R. Billings
IntroductionResidual obstructive sleep apnea (OSA) after adenotonsillectomy (T&A) is a common problem in children with Down Syndrome (DS). Our objective was to describe trends in surgical and medical management of OSA in pediatric patients with DS, and to present an algorithmic approach to managing these children.MethodsRetrospective case series of children with DS seen at a tertiary care medical center between 1/2008-6/2016 who underwent polysomnography (PSG) after having a T&A performed for sleep disordered breathing (SDB).ResultsSixty-five patients met inclusion criteria. The mean age at T&A was 4.8 years and 52.0% were male. The mean apnea-hypopnea index (AHI) was 23.2 events/hour for patients who had pre-T&A PSGs. The mean AHI was 10.7 events/hour after T&A. Twenty-three patients (35.4%) underwent at least one additional surgical procedure after T&A; 5 (7.7%) patients had ≥ two additional procedures. The most common additional surgical procedures were revision adenoidectomies (n = 8) and lingual tonsillectomies (n = 13). Fifteen (23.1%) patients underwent at least one drug-induced sleep endoscopy (DISE) to help direct selection of surgical site/s.ConclusionsResidual OSA is common after T&A in children with Down syndrome and can be managed by additional surgical interventions in many instances with successful reduction of the AHI. DISE has become part of a standard algorithm for managing persistent OSA in children with Down syndrome after T&A.



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The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions

Abstract

Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4_S228P). The functional impact by the interaction of anti-PD-1 IgG4_S228P antibody with Fc gamma receptors (FcγRs) is poorly understood. To assess the effects, we generated a pair of anti-PD-1 antibodies: BGB-A317/IgG4_S228P and BGB-A317/IgG4-variant (abbreviated as BGB-A317), with the same variable regions but two different IgG4 Fc-hinge sequences. There was no significant difference between these two antibodies in binding to PD-1. However, BGB-A317/IgG4_S228P binds to human FcγRI with high affinity and mediates crosslinking between PD-1 and FcγRI. In contrast, BGB-A317 does neither. Further cell-based assays showed that such crosslinking could reverse the function of an anti-PD-1 antibody from blocking to activating. More importantly, the crosslinking induces FcγRI⁺ macrophages to phagocytose PD-1⁺ T cells. In a mouse model transplanted with allogeneic human cancer cells and PBMCs, BGB-A317 showed significant tumor growth inhibition, whereas BGB-A317/IgG4_S228P had no such inhibition. Immunohistochemistry study revealed an inverse correlation between FcγRI⁺ murine macrophage infiltration and the density of CD8⁺PD-1⁺ human T cells within tumors in the BGB-A317/IgG4_S228P-treated group. These evidences suggested that FcγRI⁺ binding and crosslinking had negative impact on the anti-PD-1 antibody-mediated anti-cancer activity.

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Chronische myeloische Leukämie

Zusammenfassung

Die Einführung des Tyrosinkinaseinhibitors (TKI) Imatinib verbesserte die Prognose bei chronischer myeloischer Leukämie (CML) erheblich. Mit den Zweitgenerationsinhibitoren Nilotinib, Dasatinib und Bosutinib werden im Vergleich zu Imatinib raschere und tiefere molekulare Remissionen mit verändertem Nebenwirkungsprofil erzielt. Lang andauernde, behandlungsfreie Remissionen bei einer steigenden Zahl von Patienten verstärken die Hoffnung auf eine Heilbarkeit der CML. Entscheidend ist ein konsequentes zytogenetisches und molekulares Follow-up der CML-Patienten mit standardisierten Methoden, um den Remissionsstatus regelmäßig zu überprüfen. Der Einsatz von Interferon-α parallel zu oder nach einer TKI-Therapie geht mit der Induktion einer Immunantwort gegen den leukämischen Klon einher, was die Remissionsrate weiter erhöht. Ein neuer allosterischer Kinaseinhibitor (Asciminib) könnte die CML-Therapie künftig weiter verbessern.

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