Ausschreibung Thieme Teaching Award 2018

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 663-663
DOI: 10.1055/s-0043-118833

Georg Thieme Verlag KG Stuttgart · New York

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Sterblichkeit bei Sepsis: Verbesserungen scheinen schwierig

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 656-658
DOI: 10.1055/s-0043-118984

Georg Thieme Verlag KG Stuttgart · New York

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Ambulante Anästhesie: Regionalanästhesie im ambulanten Bereich

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 691-702
DOI: 10.1055/s-0042-120237

Ausgewählte Regionalanästhesieverfahren sind für den ambulant tätigen Anästhesisten eine attraktive Alternative zu Analgosedierung und Narkose – und dies bei hoher Patientenzufriedenheit und seltenen Komplikationen. Dieser Beitrag widmet sich den organisatorischen und hygienischen Anforderungen, die es dabei zu beachten gilt. Des Weiteren gehen die Autoren auf einzelne Verfahren und ihre Anwendung in unterschiedlichen Körperregionen näher ein.
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Georg Thieme Verlag KG Stuttgart · New York

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Perioperatives Vorhofflimmern: Alter und Art der Operation beeinflussen Inzidenz

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 658-658
DOI: 10.1055/s-0043-117035

Georg Thieme Verlag KG Stuttgart · New York

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Ambulante Anästhesie: Grenzen und Möglichkeiten

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 666-678
DOI: 10.1055/s-0042-120247

Ambulante Operationen werden künftig zunehmend nachgefragt werden – Ursachen sind u. a. die alternde Bevölkerung und die finanzielle Lage der Krankenkassen. Der Beitrag geht ausführlich auf Begleiterkrankungen ein, bei denen die Entscheidung ambulant oder stationär sorgfältig abgewogen werden muss. Darüber hinaus nimmt er die betriebs- und volkswirtschaftlichen Grenzen und Möglichkeiten des ambulanten Operierens unter die Lupe.
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Georg Thieme Verlag KG Stuttgart · New York

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Neuronenspezifische Enolase zur Prognose nach Herz-Kreislauf-Stillstand

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 659-660
DOI: 10.1055/s-0043-117055

Georg Thieme Verlag KG Stuttgart · New York

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Der zerebrale Notfall – wichtige anästhesiologische Aspekte

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 716-725
DOI: 10.1055/s-0042-120989

Der zerebrale Notfall ist eine häufige Notfallsituation – und das Gehirn unterscheidet sich durch seine Unersetzbarkeit und minimale Ischämietoleranz von allen anderen Organen. Dieser Beitrag verwendet bewusst den Begriff des zerebralen Notfalls und will sich so von einzelnen Erkrankungsbildern lösen. Der Fokus liegt auf der anästhesiologischen Praxis, aber auch auf dem „Notfall in uns", den jeder Notfall für das Behandlungsteam bedeuten kann.
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Georg Thieme Verlag KG Stuttgart · New York

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Paravertebrale Katheteranalgesie – wirksame Alternative zum Kaudalblock

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 660-660
DOI: 10.1055/s-0043-112726

Georg Thieme Verlag KG Stuttgart · New York

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Ambulante Anästhesie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 664-665
DOI: 10.1055/s-0043-118408

Georg Thieme Verlag KG Stuttgart · New York

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Langzeitversorgung von Patienten verbessern

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 662-663
DOI: 10.1055/s-0043-118974

Georg Thieme Verlag KG Stuttgart · New York

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Ambulante Anästhesie: Organisation in Praxis und Krankenhaus

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 679-690
DOI: 10.1055/s-0042-120238

Ambulante Anästhesie erfolgt immer im Rahmen einer ambulanten Operation – somit hängt der Erfolg davon ab, wie gut die „Einheit ambulantes Operieren" organisiert und aufeinander abgestimmt ist. Dieser Beitrag beleuchtet die vielen rechtlichen Vorgaben, die es beim ambulanten Operieren und Anästhesieren zu erfüllen gilt. Darüber hinaus werden die Organisationsstrukturen im niedergelassenen Bereich und im Krankenhaus erläutert und verglichen.
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Georg Thieme Verlag KG Stuttgart · New York

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Einfühlsame Ärzte sind die besseren Ärzte

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 662-662
DOI: 10.1055/s-0043-118976

Georg Thieme Verlag KG Stuttgart · New York

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Perioperative Anaphylaxie auf Arzneimittel

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 704-715
DOI: 10.1055/s-0043-100231

Im Rahmen eines operativen Eingriffs erhalten Patienten zahlreiche Arzneimittel. Entwickeln sie eine anaphylaktische Reaktion, so ist akut schwer zu beurteilen, welche Substanz für diese verantwortlich ist. Die meisten der intraoperativen Einschätzungen zur Ursache einer Anaphylaxie sind falsch. Umso wichtiger ist es, die verursachende Substanz später zu identifizieren, um eine Reexposition, z. B. bei einer erneuten OP, zu verhindern.
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Georg Thieme Verlag KG Stuttgart · New York

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Geburtshilfliche Anästhesie: Altbewährtes, Kontroversen und neue Perspektiven – Teil 1

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 727-736
DOI: 10.1055/s-0043-104921

In der „Whatʼs New in Obstetric Anesthesia" Lecture, die jedem an der anästhesiologischen Kreißsaalversorgung Interessierten in abgedruckter Form sehr ans Herz gelegt werden kann, werden seit 1975 durch die Society for Obstetric Anesthesia and Perinatology die im Rahmen des Annual Meeting als relevant für die klinische Versorgung erachteten Vorträge zusammengefasst. Nach dem Tode von Gerard W. Ostheimer, Professor of Anesthesiology im Brigham and Womenʼs Hospital in Boston, Massachusetts, wurde sie zur Gerard W. Ostheimer „Whatʼs New in Obstetric Anesthesia" Lecture umbenannt, um dessen Beiträge zur Regionalanästhesie und geburtshilflichen Anästhesie zu würdigen. Jedes Jahr gewährt die von ausgewählten Fachvertretern gehaltene Veranstaltung und ihr Abdruck in namhaften Anästhesie-Journalen Einblick in eine kritische Würdigung rezenter Literatur und die möglichen Konsequenzen für – aber nicht nur – die anästhesiologische Kreißsaalpraxis.Eine ähnliche Veranstaltung hat in Deutschland seit über 16 Jahren Tradition: Das Geburtshilfliche Anästhesiesymposium des Wissenschaftlichen Arbeitskreises Regionalanästhesie und Geburtshilfliche Anästhesie. Anders als in den von Einzelpersonen gehaltenen Vortragsveranstaltungen werden „Evergreens" oder „Hot Topics" der anästhesiologischen Kreißsaalversorgung in regelmäßigem Zyklus oder aus aktuellem Anlass aufgegriffen, präsentiert und vor allem diskutiert. In den Vortragsveranstaltungen offenbart sich oft wesentlich früher als in traditionellen Lehrbuchkapiteln der subtile Wandel in Hinblick auf die diskutierten Themen.Der 2-teilige Beitrag fasst das Symposium 2016 zusammen, stellt jedoch keine offizielle Meinungsbekundung seitens des Arbeitskreises dar. Teil 1 geht auf mütterliche Todesursachen während Schwangerschaft, Geburt und Stillzeit sowie strukturelle Voraussetzungen im Kreißsaal, Adipositas in der Schwangerschaft und Sepsis bei der Schwangeren und im Wochenbett ein. Teil 2 behandelt etablierte Standards und neue Perspektiven im Rahmen der geburtshilflichen Analgesie und Anästhesie bezüglich Epiduralanalgesie, postpunktionellem Kopfschmerz, Anästhesie und Analgesie während und nach Sectio, hämodynamischem Monitoring und postpartaler Blutung.
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Georg Thieme Verlag KG Stuttgart · New York

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Levosimendan bei herzchirurgischen Patienten mit linksventrikulärer Dysfunktion

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 656-656
DOI: 10.1055/s-0043-118982

Georg Thieme Verlag KG Stuttgart · New York

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Remifentanil up2date – Teil 2

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 630-639
DOI: 10.1055/s-0043-114676

Remifentanil wird seit 20 Jahren mit Erfolg in vielen Bereichen der Anästhesiologie eingesetzt. Im 1. Teil wurde die Substanz mit ihren pharmakologischen Charakteristika sowie ihren erwünschten und unerwünschten Wirkungen beschrieben. Der hier vorliegende 2. Teil befasst sich mit der Anwendung des Opioids bei speziellen Patientengruppen und in den verschiedenen anästhesiologisch betreuten Fachdisziplinen.
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Georg Thieme Verlag KG Stuttgart · New York

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Analgosedierung bei OSA-Patienten: Ist der Standard hier sinnvoll?

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 645-648
DOI: 10.1055/s-0043-114467

Georg Thieme Verlag KG Stuttgart · New York

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Katastrophenmedizin in und außerhalb der Klinik: auf das Ungeplante vorbereitet sein

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 588-593
DOI: 10.1055/s-0043-116913

Georg Thieme Verlag KG Stuttgart · New York

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Aktuell, übersichtlich und knapp

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 586-586
DOI: 10.1055/s-0042-120977

Georg Thieme Verlag KG Stuttgart · New York

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Nervenschäden nach Regionalanästhesie – welche Risikofaktoren gibt es?

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 579-580
DOI: 10.1055/s-0043-116930

Georg Thieme Verlag KG Stuttgart · New York

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Nephrotic syndrome and acute kidney injury induced by malathion toxicity

We treated a case of acute kidney injury and nephrotic syndrome after malathion inhalation. A 69-year-old Japanese man presented with oedema 15 days after inhalation of malathion, a widely used pesticide. Serum albumin was 2.4 g/dL, urinary protein 8.6 g/gCr and serum creatinine 2.5 mg/dL. Kidney biopsy revealed tubular cell damage, epithelial cell damage in glomeruli and diffuse foot process effacement in electron microscopy. Acute kidney injury progressed to treatment with dialysis. Renal function recovered after corticosteroid administration from the 43rd day after admission. Malathion inhalation should be ruled out as a differential diagnosis in individuals who develop acute kidney injury and nephrotic syndrome, especially in rural-dwelling patients.

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Radiation retinopathy treated successfully with aflibercept

Aflibercept (aflibercept) is a novel anti-vascular endothelial growth factor drug indicated for wet age-related macular degeneration and macular oedema secondary to retinal vein occlusion and diabetic macular oedema. While only newly introduced on the market, it is growing in popularity and over 5.5 million doses have been prescribed worldwide. Due to its versatile mechanism, it is indicated for numerous eye pathologies, and in particular, has been adapted to treat various types of retinopathy. To our knowledge, this is the first case report of solely using aflibercept to treat cystoid macular oedema in radiation retinopathy.

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Eosinophilic oesophagitis and coeliac disease: is there an association?

A 25-year-old man was seen in outpatient clinic for progressive solid food dysphagia. He was already medicated with a proton pump inhibitor with no improvement. His blood tests showed a slight microcytic anaemia and peripheral eosinophilia. The oesophago-gastro-duodenoscopy showed longitudinal furrows in the distal two-thirds of the oesophagus and a concentric distal stenosis. The biopsies taken showed eosinophilic infiltrates consistent with eosinophilic oesophagitis. There was no improvement with topical fluticasone, so the patient was started on a systemic corticosteroid with resolution of dysphagia and of the oesophageal stenosis. He was kept on topical steroids for symptomatic control. On repeat endoscopy, the duodenal mucosa showed multiple papules that were biopsied. Histology showed features consistent with coeliacdisease. The patient was asymptomatic but there was evidence of iron deficiency anaemia, and so a gluten-free diet was started. Despite only a partial adherence to the diet, the iron deficiency anaemia resolved.

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Traditional Chinese medicine-facilitated treatments may relieve anxiety symptoms during drug switching from methadone to buprenorphine/naloxone for treating opioid dependence

This study investigated a 51-year-old married man with a history of heroin dependence who underwent methadone maintenance treatment for 7 years. He received traditional Chinese medicine (TCM)-facilitated treatments and switched from methadone to buprenorphine/naloxone. Strong anxiety symptoms were observed during the initial stage; therefore, we prescribed a combination of Chaihu-Shugan-San, Zhi Bai Di Huang and Chin-Gin-Kuan-Ming decoction as the major herbal synergic regimen to relieve the symptoms of opioid withdrawal, anxiety and insomnia. During the treatment course, no precipitating withdrawal syndromes were noted, and the subject was gradually relieved of his anxiety symptoms through continual TCM treatments. In conclusion, TCM is effective in facilitating the switch from methadone to buprenorphine/naloxone and relieving anxiety symptoms. Therefore, focus on TCM-facilitated treatments for heroin dependence should be increased.

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All sorts of tests, only one question: an unexpected cause of hypertension

A 48-year-old woman presented to the Accident and Emergency department with a 4 month history of headaches, nausea and dizziness. She was found to have severe hypertension and hypokalaemia. Extensive investigations did not find any secondary cause for hypertension. The patient was discharged with oral doxazosin therapy which controlled the blood pressure. Before the follow-up appointment at the hypertension clinic, the patient and her husband identified that her headaches coincided with liquorice tea consumption of up to three cups per day. This information was not obtained in the clinical assessment. The patient is now headache and medication free after cessation of liquorice tea. Liquorice ingestion is often a forgotten reversible cause of hypertension. A good history is key to this diagnosis.

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Tuberculosis epididymitis complicated by a cutaneous fistula

A 63-year-old man developed scrotal swelling that became bilateral over 2 months. His symptoms persisted after treatment for epididymitis, and he developed a scrotal fistula with drainage. Mycobacterium tuberculosis grew from the urine and fistula. His symptoms resolved and fistula closed with medical therapy. His case highlights the importance of early recognition, diagnosis and treatment of this form of extrapulmonary tuberculosis.

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Pleomorphic sarcoma of the breast

Description

This is an 81-year-old man with a history of small bowel carcinoid. He was undergoing routine surveillance (every 6 months) CT chest, abdomen and pelvis with contrast, which showed an incidental left breast mass in the lower inner quadrant, 12x9 mm concerning for breast neoplasm, there was left axillary lymphadenopathy (LAD) as well (figure 1). Correlation with clinical examination, mammography and ultrasound were recommended. A left breast ultrasound noted a hypoechoic irregular mass with indistinct margins, 7 mm in size at the 10 o'clock position on the left breast, 3 cm from the nipple (figure 2). Breast imaging-reporting and data system (BI-RADS) category 4. Bilateral mammogram demonstrated a 1.3 cm irregular shaped mass at the 10 o'clock position of the left breast. No lymphadenopathy (LAD) was noted on the mammogram or ultrasound. It was categorised as BI-RADS 5 on the mammogram. Bilateral axillary ultrasonography was obtained to evaluate for...

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Dermoscopy of pseudoxanthoma elasticum

Description

A 22-year-old woman presented with complaints of gradually progressive yellowish asymptomatic papules coalescing to form plaques over the lateral aspects of the neck since last 3 years. There were no associated systemic complaints. No similar complaints were noted in any of the family members. Systemic examination was normal while mucocutaneous examination revealed the presence of symmetrically distributed yellowish monomorphic papules arranged in a linear and reticulate manner on both sides of the neck, axillae and periumbilical area (figure 1). These plaques were confluent at most of the places, occasionally studded with telangiectasias and had a pebble-like feel on palpation with poor elastic recoil. Polarised light dermoscopy at x10 magnification of these plaques showed multiple irregular yellowish areas alternating with multiple linear vessels. These yellowish plaques coalesced to form parallel strands (figure 2A). The fundus examination was within normal limits except diffuse pigmentary degeneration (figure...

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Abrikossoffs tumour on the upper limb: a rare presentation

Abrikossoff's tumour or granular cell tumour is a rare entity. Most common locations are the head and neck, with only a few cases reported on the upper limbs. A 55-year-old man with a nodular lesion on the left arm resorted to surgery consultation. Nodule was firm, mobile, painless and non-ulcerated. Total excision using a Limberg flap procedure was performed. Following 3 months of follow-up, the patient is fine. Abrikossoff's tumour is frequently presented in the second to sixth decade of life as an ulcerated nodule with progressive growth. Malignant form is rare, with metastases occurring in up to 3% of patients. Excision must be accomplished with free margins. Recurrence is rare. Abrikossoff's tumour on the upper limbs is rare. Although benignity is the rule, doctors must be aware of the possibility of harbouring a cancer. Surgery is the treatment of choice.

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Selective aplasia of global fibres of all extraocular muscles in congenital fibrosis of extraocular muscles (CFEOM): a rare presentation

Description

A 15-year-old boy presented in our strabismus clinic with complaints of bilateral ptosis and limitation of ocular movements since birth. He had a positive family history of consanguinity and similar ocular movement abnormalities in his three siblings. There was no history of systemic illness. Physical examination showed normal growth parameters without craniofacial dysmorphism except blepharoptosis and lagophthalmos in both eyes, more marked in the right eye. Right eye best-corrected visual acuity (BCVA) was 6/12 and left eye BCVA was 6/9. Slit-lamp biomicroscopy of right eye showed exposure keratopathy, rest was unremarkable. Fundus examination was within normal limits, with no pigmentary retinopathy or optic atrophy changes. There was almost total external ophthalmoplegia, with normal reacting pupils to both direct and consensual light reflex in each eye. The patient preferred fixation with the left eye as his right eye had severe ptosis covering the pupillary area. The patient had chin up and 15° right...

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Heart failure in dilated cardiomyopathy mimicking asthma triggered by pneumonia

Heart failure is a rare cause of wheezing and may develop into a critical condition in children. Few cases report patients with heart failure, secondary to dilated cardiomyopathy, with high fever. A 23-month-old girl visited the emergency department with high fever, cough, first wheezing episode, chest retraction and tachycardia. The chest X-ray revealed consolidation on the left lower lung field; the cardiothoracic ratio was 60%. She was diagnosed with bronchial asthma triggered by pneumonia, which remained unchanged during four visits. Subsequently, she was diagnosed with heart failure in idiopathic dilated cardiomyopathy and discharged without sequelae. During the first wheezing episode in children with abnormal vital signs, heart failure should be considered in the differential diagnosis, and a chest X-ray should be performed. Additionally, when the cardiothoracic ratio is greater than 50%, 12-lead ECG and echocardiography should be performed. Moreover, cognitive bias should be considered in all emergency care unit situations.

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Vancomycin-resistant Enterococcus faecium bacteraemia as a complication of Kayexalate (sodium polystyrene sulfonate, SPS) in sorbitol-induced ischaemic colitis

We present the case report of an 80-year-old woman with chronic kidney disease stage G5 admitted to the hospital with fluid overload and hyperkalaemia. Sodium polystyrene sulfonate (SPS, Kayexalate) in sorbitol suspension was given orally to treat her hyperkalaemia, which precipitated an episode of SPS in sorbitol-induced ischaemic colitis with the subsequent complication of vancomycin-resistant Enterococcus (VRE) bacteraemia. SPS (Kayexalate) in sorbitol suspension has been implicated in the development of intestinal necrosis. Sorbitol, which is added as a cathartic agent to decrease the chance of faecal impaction, may be primarily responsible through several proposed mechanisms. The gold standard of diagnosis is the presence of SPS crystals in the colon biopsy. On a MEDLINE search, no previous reports of a VRE bacteraemia as a complication of biopsy-confirmed SPS in sorbitol ischaemic colitis were found. To the best of our knowledge, ours would be the first such case ever reported.

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Giant atrium, giant clot: need for anticoagulation

Description

We present a patient with medical history of atrial fibrillation, rheumatic mitral valve stenosis and ulcerative colitis who came to the emergency room with onset of bilateral lower extremity pain 2 hours prior to presentation. On examination, feet were pale, cold and pulses were absent. Patient used to be on warfarin for atrial fibrillation which was discontinued 1 month ago by his primary care physician due to recurrent bleeding. Atrial fibrillation with controlled ventricular response was seen on ECG. Emergent arterial Doppler revealed occlusion of the bilateral calf arteries at the level of the tibioperoneal trunk. Patient underwent emergent bilateral right and left groin exploration with bilateral embolectomy and thromboembolectomy. Restoration of flow with no haemodynamically significant atheromatous changes was confirmed by repeat Doppler. Echocardiography revealed severely dilated left atrium measuring 10 cm x 7 cm with large left atrial thrombi (figure 1, online) and severe mitral valve stenosis (mean gradient...

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Atraumatic bilateral humeral head fracture secondary to single seizure

Description

Case 1: A 51-year-old man presented with a single unprovoked generalised tonic clonic seizure (GTCSz), lasting for 4 min, he developed postseizure bilateral shoulder pain and was unable to move his arms as they were painful; there was a history of seizure 7 years ago, he was not on any antiepileptic drugs (AEDs). His sX-ray shoulder showed bilateral comminuted humeral head fracture, which was confirmed by CT of shoulders, see figure 1.He was started on AEDs from a seizure perspective. His neuroimaging, which included an MRI brain (epilepsy protocol) and electroencephalogram (EEG), were normal, see figure 1. From a shoulder management perspective, he was transferred to an orthopaedic surgeon which resulted in corrective surgery.

Figure 1

X-ray and CT of shoulders showing bilateral comminuted humeral head fracture and fracture fragment displacement.

Case 2: A 65-year-old man presented with first seizure of his lifetime, GTCSz, lasting for 3 min, developed...

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Pelvic bone anatomy vs implanted gold seed marker registration for image-guided intensity modulated radiotherapy for prostate carcinoma: Comparative analysis of inter-fraction motion and toxicities

Publication date: Available online 9 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Madhup Rastogi, Sambit Swarup Nanda, Ajeet Kumar Gandhi, Divakar Dalela, Rohini Khurana, Surendra Prasad Mishra, Anoop Srivastava, S. Farzana, Madan Lal Brahma Bhatt, Nuzhat Husain
ObjectivesWe compared the prostate motion variability and toxicities between patients treated with gold marker registration based IG-IMRT (IG-IMRT-M) and bony landmark registration based IG-IMRT (IG-IMRT-B).MethodsT1c-T3b (node negative), intermediate and high risk (non-metastatic) adenocarcinoma of prostate, age ≥18years, Karnofsky Performance Status of ≥70 were included in this retrospective study. The prostate motion variability, acute and late radiation toxicities between the two treatment arms (IG-IMRT-M versus IG-IMRT-B) were compared.ResultsTotal of 35 patients (17 for IG-IMRT-M and 18 for IG-IMRT-B) were treated with a median radiotherapy dose of 76 Gray. The prostate variability observed with and without markers in millimeter was 4.1±2.3 vs 3.7±2.1 [Antero-Posterior (A-P); p=0.001], 2.3±1.5 vs 2.1±1.2 [Superior-Inferior (S-I); p=0.095] and 1.1±1.7 vs 0.4±1.4 [Left-Right (L-R); p=0.003]. There was higher acute toxicity in IG-IMRT-B arm compared to IG-IMRT-M arm in terms of grade ≥2 diarrhea [50% vs 11% OR=7.5 (1.3–42.7); p=0.02] and grade ≥2 proctitis [38% vs 5.8%, OR=10.1 (1.09–94.1); p=0.04]. At a median follow up of 36months, the late genitourinary toxicities grade ≥2 [27% vs 0%; p=0.04] were higher in the IG-IMRT-B arm compared to IG-IMRT-M arm.ConclusionsIG-IMRT-M detects higher prostate motion variability as compared to IG-IMRT-B, inferring a significant prostate motion inside fixed pelvic bony cavity. The addition of marker based image guidance results in higher precision of prostate localization and lesser acute and late toxicities.



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Pelvic bone anatomy vs implanted gold seed marker registration for image-guided intensity modulated radiotherapy for prostate carcinoma: Comparative analysis of inter-fraction motion and toxicities

Publication date: Available online 9 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Madhup Rastogi, Sambit Swarup Nanda, Ajeet Kumar Gandhi, Divakar Dalela, Rohini Khurana, Surendra Prasad Mishra, Anoop Srivastava, S. Farzana, Madan Lal Brahma Bhatt, Nuzhat Husain
ObjectivesWe compared the prostate motion variability and toxicities between patients treated with gold marker registration based IG-IMRT (IG-IMRT-M) and bony landmark registration based IG-IMRT (IG-IMRT-B).MethodsT1c-T3b (node negative), intermediate and high risk (non-metastatic) adenocarcinoma of prostate, age ≥18years, Karnofsky Performance Status of ≥70 were included in this retrospective study. The prostate motion variability, acute and late radiation toxicities between the two treatment arms (IG-IMRT-M versus IG-IMRT-B) were compared.ResultsTotal of 35 patients (17 for IG-IMRT-M and 18 for IG-IMRT-B) were treated with a median radiotherapy dose of 76 Gray. The prostate variability observed with and without markers in millimeter was 4.1±2.3 vs 3.7±2.1 [Antero-Posterior (A-P); p=0.001], 2.3±1.5 vs 2.1±1.2 [Superior-Inferior (S-I); p=0.095] and 1.1±1.7 vs 0.4±1.4 [Left-Right (L-R); p=0.003]. There was higher acute toxicity in IG-IMRT-B arm compared to IG-IMRT-M arm in terms of grade ≥2 diarrhea [50% vs 11% OR=7.5 (1.3–42.7); p=0.02] and grade ≥2 proctitis [38% vs 5.8%, OR=10.1 (1.09–94.1); p=0.04]. At a median follow up of 36months, the late genitourinary toxicities grade ≥2 [27% vs 0%; p=0.04] were higher in the IG-IMRT-B arm compared to IG-IMRT-M arm.ConclusionsIG-IMRT-M detects higher prostate motion variability as compared to IG-IMRT-B, inferring a significant prostate motion inside fixed pelvic bony cavity. The addition of marker based image guidance results in higher precision of prostate localization and lesser acute and late toxicities.



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Acute reversible toxic encephalopathy during capecitabine and oxaliplatin treatment

Journal of Oncology Pharmacy Practice, Ahead of Print.


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Deficiency in protein tyrosine phosphatase PTP1B shortens lifespan and leads to development of acute leukemia

Protein tyrosine phosphatase PTP1B is a critical regulator of signaling pathways controlling metabolic homeostasis, cell proliferation and immunity. In this study, we report that global or myeloid-specific deficiency of PTP1B in mice decreases lifespan. We demonstrate that myeloid-specific deficiency of PTP1B is sufficient to promote the development of acute myeloid leukemia (AML). LysM-PTP1B-/- mice lacking PTP1B in the innate myeloid cell lineage displayed a dysregulation of bone marrow cells with a rapid decline in population at midlife and a concomitant increase in peripheral blood blast cells. This phenotype manifested further with extramedullary tumors, hepatic macrophage infiltration and metabolic reprogramming, suggesting increased hepatic lipid metabolism prior to overt tumor development. Mechanistic investigations revealed an increase in anti-inflammatory M2 macrophage responses in liver and spleen, as associated with increased expression of arginase I and the cytokines IL-10 and IL-4. We also documented STAT3 hypersphosphorylation and signaling along with JAK-dependent upregulation of anti-apoptotic proteins Bcl2 and BclXL. Our results establish a tumor suppressor role for PTP1B in the myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia.

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Deficiency in protein tyrosine phosphatase PTP1B shortens lifespan and leads to development of acute leukemia

Protein tyrosine phosphatase PTP1B is a critical regulator of signaling pathways controlling metabolic homeostasis, cell proliferation and immunity. In this study, we report that global or myeloid-specific deficiency of PTP1B in mice decreases lifespan. We demonstrate that myeloid-specific deficiency of PTP1B is sufficient to promote the development of acute myeloid leukemia (AML). LysM-PTP1B-/- mice lacking PTP1B in the innate myeloid cell lineage displayed a dysregulation of bone marrow cells with a rapid decline in population at midlife and a concomitant increase in peripheral blood blast cells. This phenotype manifested further with extramedullary tumors, hepatic macrophage infiltration and metabolic reprogramming, suggesting increased hepatic lipid metabolism prior to overt tumor development. Mechanistic investigations revealed an increase in anti-inflammatory M2 macrophage responses in liver and spleen, as associated with increased expression of arginase I and the cytokines IL-10 and IL-4. We also documented STAT3 hypersphosphorylation and signaling along with JAK-dependent upregulation of anti-apoptotic proteins Bcl2 and BclXL. Our results establish a tumor suppressor role for PTP1B in the myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia.

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NIH Initiative Aims to Improve Immunotherapy [News in Brief]

Collaboration seeks to discover and standardize cancer biomarkers.

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Genetic predictors of response to systemic therapy in esophagogastric cancer [Research Briefs]

The incidence of esophagogastric cancer is rapidly rising but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of metastatic esophagogastric cancer patients. There was no association between HRD defects and response to platinum-based chemotherapy. Patients with MSI-H tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single EBV+ patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and co-mutations in the receptor tyrosine kinase, RAS, PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab, and guide strategies to overcome drug resistance.

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Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer, Published online: 09 November 2017; doi:10.1038/bjc.2017.279

http://ift.tt/2zKFBt0

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?, Published online: 09 November 2017; doi:10.1038/bjc.2017.386

http://ift.tt/2zLhp9R

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM, Published online: 09 November 2017; doi:10.1038/bjc.2017.385

http://ift.tt/2zqMgIr

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients, Published online: 09 November 2017; doi:10.1038/bjc.2017.397

http://ift.tt/2zLhjiv

IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer

IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer

IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer, Published online: 09 November 2017; doi:10.1038/bjc.2017.377

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A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline, Published online: 09 November 2017; doi:10.1038/bjc.2017.365

http://ift.tt/2zLKCli

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma, Published online: 09 November 2017; doi:10.1038/bjc.2017.401

http://ift.tt/2zrNtPG

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer, Published online: 09 November 2017; doi:10.1038/bjc.2017.279

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Combining DNA damaging therapeutics with immunotherapy: more haste, less speed

Combining DNA damaging therapeutics with immunotherapy: more haste, less speed

Combining DNA damaging therapeutics with immunotherapy: more haste, less speed, Published online: 09 November 2017; doi:10.1038/bjc.2017.376

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Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?, Published online: 09 November 2017; doi:10.1038/bjc.2017.386

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BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM, Published online: 09 November 2017; doi:10.1038/bjc.2017.385

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Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients, Published online: 09 November 2017; doi:10.1038/bjc.2017.397

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IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer

IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer

IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer, Published online: 09 November 2017; doi:10.1038/bjc.2017.377

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A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline, Published online: 09 November 2017; doi:10.1038/bjc.2017.365

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Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma, Published online: 09 November 2017; doi:10.1038/bjc.2017.401

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Clinical characteristics and outcomes of Castleman disease: a multicenter study of 185 Chinese patients

Summary

Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. 121 patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%) and mixed type for 3 patients (1.6%). The 5-year overall survival (OS) of 185 CD cases was 80.3%. All UCD patients underwent surgical excision, while the treatment strategies of MCD patients were heterogeneous. The outcome for UCD patients was better than MCD patients, with 5-year OS rates of 93.6% and 51.2%, respectively. In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. This multicenter study comprising the largest sample size to date suggested that MCD is a distinct entity from UCD with a significantly worse outcome. Older age (≥40 years), splenomegaly and hypoalbuminemia were risk factors for poorer MCD prognosis.

This article is protected by copyright. All rights reserved.

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Stool- and Blood-Based Molecular Tests in Screening for Colorectal Cancer: Ready for Prime Time?

Abstract

Purpose of Review

This article serves as a critical review and summary of the role of stool- and blood-based molecular tests for colorectal cancer (CRC) screening indexed in PubMed between 2011 and early 2017. In particular, we focus on assays approved for clinical use and recent findings on novel biomarkers. The biological rationale, clinical performance characteristics, and limitations of these tools are discussed.

Recent Findings

Novel miRNA markers and bacterial DNA markers have been reported and evaluated in case-controlled studies. The plasma-based SEPT9 test and the multi-target stool DNA test (mt-sDNA) have received approval for CRC screening and are available to patients. Mt-sDNA has demonstrated a high accuracy rate in detecting colorectal neoplasia.

Summary

Despite the proven benefits of CRC screening, a large percentage of the eligible population remains unscreened due to suboptimal screening compliance and the limitations of current modalities. The opportunity to improve CRC screening rates has driven research to develop novel screening approaches. Stool- and blood-based molecular tests have demonstrated significant potential for improving access to CRC screening.

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Clinical characteristics and outcomes of Castleman disease: a multicenter study of 185 Chinese patients

Summary

Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. 121 patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%) and mixed type for 3 patients (1.6%). The 5-year overall survival (OS) of 185 CD cases was 80.3%. All UCD patients underwent surgical excision, while the treatment strategies of MCD patients were heterogeneous. The outcome for UCD patients was better than MCD patients, with 5-year OS rates of 93.6% and 51.2%, respectively. In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. This multicenter study comprising the largest sample size to date suggested that MCD is a distinct entity from UCD with a significantly worse outcome. Older age (≥40 years), splenomegaly and hypoalbuminemia were risk factors for poorer MCD prognosis.

This article is protected by copyright. All rights reserved.

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Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy

Abstract

Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4–L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states.

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Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy

Abstract

The development of cardiac hypertrophy is a complicated process, which undergoes a transition from compensatory hypertrophy to heart failure, and the identification of new biomarkers and targets for this disease is greatly needed. Here we investigated the development of isoproterenol (ISO)-induced cardiac hypertrophy in an in vitro experimental model. After the induction of hypertrophy with ISO treatment in H9c2 cells, cell surface area, cell viability, cellular reactive oxygen species (ROS), and nitric oxide (NO) levels were tested. Our data showed that the cell viability, mitochondrial membrane potential, and NO/ROS balance varied during the development of cardiac hypertrophy in H9c2 cells. It was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2 (Prdx2) was decreased during the cardiac hypertrophy of H9c2 cells. These results suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2 cells and in the transition from compensated hypertrophy to de-compensated hypertrophy in H9c2 cells, and our findings may have important implications for the management of this disease.

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Immature colon carcinoma transcript-1 promotes proliferation of gastric cancer cells

Abstract

Gastric cancer is the fourth most common malignant tumor and has been considered as one of the leading causes of cancer-related death worldwide. The identification of the molecular mechanism during gastric cancer progression is urgently needed, which will help to develop more effective treatment strategies. As a component of the human mitoribosome, immature colon carcinoma transcript-1 (ICT1) might be involved in tumor formation and progression. However, its biological function and the corresponding mechanism in gastric cancer have been poorly characterized. To study the mechanism of ICT1 in gastric cancer, we first investigated the mRNA levels of ICT1 in human normal and gastric cancer tissues using datasets from the publicly available Oncomine database. The results showed that ICT1 is overexpressed in gastric cancer tissues. Then in order to study the role of ICT1 in gastric cancer, two shRNAs were used to silence ICT1 in MGC80-3 and AGS cells. Functional analysis showed ICT1 knockdown significantly inhibited the proliferation of gastric cancer cells and induced apoptosis. Further, mechanistic study demonstrated that ICT1 silencing induced cell-cycle arrest at G2/M phase via the suppression of cyclin A2 and cyclin B1. In addition, ICT1 silencing also increased cleaved caspase-3 and activated PARP in gastric cancer cells. These findings suggest that ICT1 may play a crucial role in promoting gastric cancer proliferation in vitro.

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sTLR4/MD-2 complex inhibits colorectal cancer migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation

Abstract

Long non-coding RNAs (lncRNAs) have multiple functions in gene regulation and during cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) have not yet been well understood. In our previous study, we demonstrated that sTLR4/MD-2 complex can inhibit CRC in vitro and in vivo by targeting LPS. Therefore, the aim of the present study is to investigate the expression of lncRNA H19 in CRC and to evaluate its effect on the inhibition of sTLR4/MD-2 complex. The expression of H19 is measured in 63 CRC tumor tissues and adjacent normal tissues by quantitative real-time PCR (qRT-PCR). The effects of H19 on migration and invasiveness are evaluated by wound healing assay, migration and invasion assays. Results showed that H19 is significantly overexpressed in cancerous tissues and CRC cell lines compared with adjacent normal tissues and a normal human intestinal epithelial cell line. Moreover, H19 overexpression is closely associated with CRC patients. Our in vitro data indicated that knockdown of H19 inhibits the migration and invasiveness of CRC cells. And in vivo sTLR4/MD-2 complex inhibits tumor growth in mice and the expression of H19 is down-regulated. These results suggest that sTLR4/MD-2 complex inhibits CRC migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

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Endothelial cells modified by adenovirus vector containing nine copies hypoxia response elements and human vascular endothelial growth factor as the novel seed cells for bone tissue engineering

Abstract

Vascularization is one of the hotspots during the development of new therapeutic strategies for bone tissue engineering, which can alleviate hypoxic circumstance and prevent transplant failure. Vascular endothelial growth factor (VEGF) gene transfection using recombinant adenovirus (Ad) vector can effectively promote angiogenesis, but uncontrolled long-term continuous expression of VEGF brings safety concern. Here we constructed a recombinant Ad vector containing nine copies of HRE promoter and the hVEGF165 gene, which conserved the oxygen sensitivity of hypoxia-inducible factor-1/hypoxia response elements (HIF-1/HRE). After transfection into human umbilical vein endothelial cells (HUVEC), the hVEGF165 mRNA and protein levels were much higher in response to hypoxia, as revealed by RT-PCR and ELISA, respectively. Furthermore, Ad-9HRE-hVEGF165 vector effectively promoted proliferation, migration and tube formation of HUVEC under hypoxic conditions. Thus we believe that the Ad-9HRE-hVEGF165 vector can contribute to the regulation of vascularization, which may provide a new approach for a better control of the expression of hVEGF165 during bone tissue engineering.

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Effects of 12 C 6+ heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells

Abstract

The heavy ion beam is considered to be the ideal source for radiotherapy. The p53 tumor suppressor gene senses DNA damage and transducts intracellular apoptosis signals. Previous reports showed that the heavy ion beam can trigger complex forms of damage to cellular DNA, leading to cell cycle arrest and apoptosis of HepG2 human liver cancer cells; however, the mechanisms remains unclear fully. In order to explore whether the intrinsic or extrinsic pathway participates this process, HepG2 cells were treated with ¹²C⁶⁺ HIB irradiation at doses of 0 (control), 1, 2, 4, and 6 Gy with various methods employed to understand relevant mechanisms, such as detection of apoptosis, cell cycle, and Fas expression by flow cytometry, analysis of apoptotic morphology by electron microscopy and laser scanning confocal microscopy, and screening differentially expressed genes relating to p53 signaling pathway by PCR-array assay following with any genes confirmed by western blot analysis. This study showed that ¹²C⁶⁺ heavy ion beam irradiation at a dose of 6 Gy leads to endogenous DNA double-strand damage, G2/M cell cycle arrest, and apoptosis of human HepG2 cells via synergistic effect of the extrinsic and intrinsic pathways. Differentially expressed genes in the p53 signaling pathway related to DNA damage repair, apoptosis, cycle regulation, metastasis, deterioration and radioresistance were also discovered. Consequently, the expressions of Fas, TP53BP2, TP53AIP1, and CASP9 were confirmed upregulated after ¹²C⁶⁺ HIB irradiation treatment. In conclusion, this study demonstrated the mechanisms of inhibition and apoptosis induced by ¹²C⁶⁺ heavy ion beam irradiation on HepG2 cancer cells is mediated by initiation of the biological function of p53 signaling pathway including extrinsic and intrinsic apoptosis pathway.

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Elabela-APJ axis: a novel therapy target for cardiovascular diseases

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Lipopolysaccharide promotes angiogenesis in mice model of HCC by stimulating hepatic stellate cell activation via TLR4 pathway

Abstract

Angiogenesis plays a key role in the progression of hepatocellular carcinoma (HCC). This study aimed to investigate whether lipopolysaccharide (LPS) could promote HCC angiogenesis and the role of hepatic stellate cell (HSC) in this process. In vivo orthotopic HCC model and the effect of LPS on HSC in vitro were studied. Our results demonstrated that LPS-induced HSC activation during the promotion of HCC growth and angiogenesis in mice. The LPS-TLR4 (Toll-like receptor 4) pathway in HSC is responsible for HCC angiogenesis. LPS-induced secretion of pro-angiogenic factors from HSC could promote endothelial cell migration and tubulogenesis. This study suggests that LPS acts with HSC in tumor stroma and promotes the secretion of pro-angiogenic factors that increase angiogenesis in HCC.

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Doxycycline synergizes with doxorubicin to inhibit the proliferation of castration-resistant prostate cancer cells

Abstract

Castration-resistant prostate cancer (CRPC) is fatal and there is currently no effective clinical treatment. The antibiotic doxycycline has shown anti-cancer effect in several kinds of solid tumors including prostate cancer. In this study, a combination of doxycycline and doxorubicin was used to investigate the synergistic effect on CRPC cells. MTT assay was employed to determine the viability of cells in two-dimensional (2D) cultures. Apoptosis was determined by Annexin V/propidium iodide (PI) double staining assay. Cell cycle was analyzed by PI staining, and reverse transcription-PCR (RT-PCR) was used to determine the expressions of apoptosis-related genes at mRNA level. Western blot analysis was used to analyze the expressions of Bcl-2, Bax, and Poly (ADP-ribose) polymerase proteins. Cytotoxicity assay and morphological observation of PC3 cells in three-dimensional (3D) cultures were used to determine the effect of combination treatment. Results showed that doxycycline combined with doxorubicin significantly inhibited PC3 cells in both 2D and 3D cultures, enhanced apoptosis, and increased the accumulation of cells in G2/M phase. RT-PCR showed down-regulation of Bcl-2 and up-regulation of Bax mRNA after combination treatment. Meanwhile, western blot analysis showed that combination treatment resulted in down-regulation of Bcl-2 protein and up-regulation of Bax protein, and that PARP cleavage was obviously exhibited after combination treatment. Confocal imaging analysis indicated that doxorubicin penetrated deeply into the core of spheroids when combined with doxycycline. These data indicated that doxycycline in combination with doxorubicin had a synergistic effect on PC3 cells and may provide a potential novel strategy for the treatment of CRPC.

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Response of human non-small-cell lung cancer cells to the influence of Wogonin with SGK1 dynamics

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Lysine acetylation regulates the activity of Escherichia coli pyridoxine 5′-phosphate oxidase

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Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

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Combining DNA damaging therapeutics with immunotherapy: more haste, less speed

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Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

http://ift.tt/2i00p5z

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

http://ift.tt/2ApqgdX

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

http://ift.tt/2hYWyWh

A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

http://ift.tt/2i0cFTm

Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

http://ift.tt/2AoD18A

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer

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Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

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BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM

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Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients

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IGF-1R: SUMO-ing its weight in chemoresistant colorectal cancer

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A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline

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Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma

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Neoadjuvant Therapy with Weekly Nanoparticle Albumin‐Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011‐02), a Multicenter, Non‐Randomized, Phase II Trial, with a Companion Biomarker Analysis

AbstractBackground.Nanoparticle albumin‐bound paclitaxel (nab‐Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab‐Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor‐positive (ER+), human epidermal growth factor receptor 2‐negative (HER2‐) disease.Materials and Methods.Women with ER+, HER2‐, stage II–III BC were treated preoperatively with four cycles of weekly nab‐Paclitaxel (150 mg/m2), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.Results.Eighty‐one patients with a median age of 47 years were treated; 64.2% were premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate was 28.4% (95% confidence interval [CI]: 18.6%–38.2%), RCB 0+I (good response) rate was 24.7% (95% CI: 15.3%–34.1%) and RCB 0 (complete response) rate was 7.4% (95% CI: 1.7%–13.1%). Objective response rate by magnetic resonance imaging was 76.5% and rate of conversion to breast conserving surgery was 40.0%. The most frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients, respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3 were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein, acidic, cysteine‐rich (SPARC) overexpression was significantly associated with RCB 0 (odds ratio: 0.079; 95% CI: 0.009–0.689; p = .0216).Conclusion.Despite failing to confirm an RCB III rate ≤16% in nab‐Paclitaxel‐treated patients, the RCB 0+I rate indicates a significant drug antitumor activity with low rates of grade 3–4 toxicity. Our exploratory biomarker analysis suggests a potential predictive role of complete response for SPARC. Confirmatory analyses are warranted, adapting dose and schedule to decrease peripheral neurotoxicity. (Trial registration: European Clinical Trials Database study number: 2011‐004476‐10; ClinicalTrials.gov: NCT01565499).Implications for Practice.The pathological response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle albumin‐bound paclitaxel administered as neoadjuvant treatment for early estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative disease was evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests secreted protein, acidic, cysteine‐rich overexpression in tumor cells as a potential predictor of complete response (RCB 0). Findings point to an encouraging single‐agent neoadjuvant treatment with low toxicity, which warrants future research and development.

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Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents

AbstractTumor lysis syndrome (TLS) is an uncommon but potentially life‐threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B‐cell lymphoma‐2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.Implications for Practice.Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.

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Are Disagreements in Caregiver and Patient Assessment of Patient Health Associated with Increased Caregiver Burden in Caregivers of Older Adults with Cancer?

AbstractBackground.As patients age, caregivers increasingly provide essential support and patient information. We sought to determine if patient‐caregiver assessments of patient health differ and if differences contribute to burden in caregivers of older adults with cancer.Materials and Methods.One hundred patients, aged ≥65, and their caregivers independently assessed patient function, comorbidity, nutrition, social activity, social support, and mental health. Caregivers completed the Caregiver Strain Index (CSI). Patient‐caregiver assessments were compared using the Wilcoxon signed rank test and paired t test. Association between caregiver burden and differences between patient‐caregiver assessments was examined using generalized linear regression.Results.Median patient age was 70 (range 65–91) and 70% had advanced disease. Sixty percent of patients reported requiring help with instrumental activities of daily living (IADLs); most had good social support (median Medical Outcomes Study [MOS]‐Social Support Survey score 92) and mental health (median Mental Health Inventory score 85).Caregivers were a median age of 66 (range 28–85), 73% female, 68% spousal caregivers, and 79% lived with the patient. Caregivers rated patients as having poorer physical function (more IADLs dependency [p = .008], lower Karnofsky Performance Status [p = .02], lower MOS‐Physical Function [p < .0001]), poorer mental health (p = .0002), and having more social support (p = .03) than patients themselves. Three‐quarters of caregivers experienced some caregiver burden (mean CSI score 3.1). Only differences in patient‐caregiver assessment of the patient's need for help with IADLs were associated with increased caregiver burden (p = .03).Conclusion.Patient‐caregiver assessments of patient function, mental health, and social support differ. However, only differences in assessment of IADLs dependency were associated with increased caregiver burden.Implications for Practice.As patients age, there is a higher incidence of frailty and cognitive impairments. As a result, caregivers play an increasingly vital role in providing information about patient health to healthcare providers, which is used to help healthcare providers tailor treatments and optimize patient health. These findings highlight that caregiver reporting in older adults with cancer may not replace patient reporting in those older adults who are otherwise able to self‐report. Furthermore, clinicians should check for caregiver burden in caregivers who report providing more help with instrumental activities of daily living than patients themselves report and provide appropriate support as needed.

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Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers

AbstractBackground.The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival.Materials and Methods.In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined.Results.Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated with hormone receptors negativity, HER2 positivity, and c‐kit expression. Tertiary lymphoid structures were significantly related to better disease‐free survival (DFS) in HER2 positive (HER2+) breast cancers (log‐rank = 4.054), which was not dependent on high TIL status. The combined TLS and TIL status was an independent favorable factor associated with DFS in those cases. Interestingly, tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It was associated with LVI in HER2 negative (HER2−) TLS positive (particularly estrogen receptor positive [ER+] HER2−) cases. In the ER+ HER2− cases, tumor cell infiltration into TLS was also associated with increased pathologic nodal stage (pN) stage and nodal involvement.Conclusion.Tertiary lymphoid structures showed a similar relationship with clinicopathologic features and biomarkers as TIL. The presence of TLS, irrespective of TIL level, could be an important favorable prognostic indicator in HER2+ breast cancer patients. Given the significance of TLS in promoting effective antitumor immunity, further understanding of its organization and induction may provide new opportunities to improve the current immunotherapy strategies.Implications for Practice.Despite recent interest on the clinical value of tumor infiltrating lymphocyte (TIL), little was known on the clinical significance on their spatial organization as tertiary lymphoid structures (TLS). Although TLS showed similar relationships with clinicopathologic features and biomarkers as TIL, the prognostic value of TLS, particularly in HER2 positive cancers, was independent of TIL. Moreover, tumor infiltration could be present in TLS which appears to be related to tumor invasion in HER2 negative cancers. Overall, the results demonstrated the additional value for TLS in HER2 cancer subtypes. Further investigations and its standardized evaluation will enhance its use as standard practice.

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Development of Palliative Care in China: A Tale of Three Cities

AbstractBackground.China is the most populous country in the world, but access to palliative care is extremely limited. A better understanding of the development of palliative care programs in China and how they overcome the barriers to provide services would inform how we can further integrate palliative care into oncology practices in China. Here, we describe the program development and infrastructure of the palliative care programs at three Chinese institutions, using these as examples to discuss strategies to accelerate palliative care access for cancer patients in China.Methods.Case study of three palliative care programs in Chengdu, Kunming, and Beijing.Results.The three examples of palliative care delivery in China ranged from a comprehensive program that includes all major branches of palliative care in Chengdu, a program that is predominantly inpatient‐based in Kunming, and a smaller program at an earlier stage of development in Beijing. Despite the numerous challenges related to the limited training opportunities, stigma on death and dying, and lack of resources and policies to support clinical practice, these programs were able to overcome many barriers to offer palliative care services to patients with advanced diseases and to advance this discipline in China through visionary leadership, collaboration with other countries to acquire palliative care expertise, committed staff members, and persistence.Conclusion.Palliative care is limited in China, although a few comprehensive programs exist. Our findings may inform palliative care program development in other Chinese hospitals.Implications for Practice.With a population of 1.3 billion, China is the most populous country in the world, and cancer is the leading cause of death. However, only 0.7% of hospitals offer palliative care services, which significantly limits palliative care access for Chinese cancer patients. Here, we describe the program development and infrastructure of three palliative care programs in China, using these as examples to discuss how they were able to overcome various barriers to implement palliative care. Lessons from these programs may help to accelerate the progress of palliative cancer care in China.

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Disparities of Trastuzumab Use in Resource‐Limited or Resource‐Abundant Regions and Its Survival Benefit on HER2 Positive Breast Cancer: A Real‐World Study from China

AbstractBackground.Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real‐world data are lacking, the present research was conducted to evaluate the actual use of and the effectiveness of trastuzumab in the real world in China.Methods.Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010–2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real‐world research.Results.Of 1,017 patients with early stage breast cancer (EBC), 40.5% (412/1,017) received trastuzumab therapy. Patients with EBC in resource‐abundant regions (gross domestic product per capita >$15,000 and trastuzumab included in Medicare) are more likely to receive trastuzumab than those in resource‐limited regions (37.3% vs. 13.0%, p < .05). After metastasis, 50.8% (366/720) patients received trastuzumab as their first‐line therapy. More than 10% of patients with metastatic breast cancer (MBC) continued trastuzumab therapy after twice progression in resource‐abundant regions, whereas more than 40% of patients never received any trastuzumab therapy during the whole course of therapy in resource‐limited regions. Overall, the improvement in survival for trastuzumab versus non‐trastuzumab was substantial in EBC (hazard ratio [HR] = 0.609, 95% confidence interval [CI]: 0.505–0.744) and in MBC (HR = 0.541, 95% CI: 0.418–0.606). This association was greater for patients with MBC who had never received trastuzumab (HR = 0.493, 95% CI: 0.372–0.576) than for those who had received adequate trastuzumab therapy in EBC stage (HR = 0.878, 95% CI: 0.506–1.431).Conclusion.This study showed great disparities in trastuzumab use in different regions and different treatment stages. Both EBC and MBC patients can benefit from trastuzumab, as the survival data show; however, when trastuzumab is adequate in the early stage, a further trastuzumab‐based therapy in first‐line treatment of MBC will be ineffective, especially for those with short disease‐free survival, and a second line of anti‐HER2 therapy will be recommended. (Research number: CSCO‐BC RWS 15001).Implications for Practice.This article explores the disparities in the rates of trastuzumab use due to the inequitable allocation of medical resources in China. The irrational use can be found both in resource‐abundant regions and in resource‐limited regions. Although trastuzumab‐based therapy improved survival, the actual use of trastuzumab in the early stage of breast cancer may influence the subsequent therapeutic effect after metastasis. These findings from real‐world research could help to optimize HER2 therapy after metastasis, especially in regions with limited access to these expensive targeted drugs.

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The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy

AbstractOn November 19, 2015, a marketing authorization valid through the European Union was issued for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.In a phase III trial in patients with relapsed MM, median progression‐free survival (PFS) for patients treated with carfilzomib in combination with lenalidomide and dexamethasone (CRd) was 26.3 months versus 17.6 months for those receiving lenalidomide and dexamethasone alone (hazard ratio = 0.69; 95% confidence interval, 0.57–0.83; one‐sided log‐rank p value < .0001). The most frequently observed toxicity (grade ≥3, treatment arm vs. control arm) in the phase III trial included neutropenia (29.6% vs. 26.5%), anemia (17.9% vs. 17.7%), thrombocytopenia (16.8% vs. 12.3%), pneumonia (12.5% vs. 10.5%), fatigue (7.7% vs. 6.4%), hypertension (4.6% vs. 2.1%), diarrhea (3.8% vs. 4.1%), and respiratory tract infection (4.1% vs. 2.1%).The objective of this article is to summarize the scientific review of the application leading to regulatory approval in the European Union. The scientific review concluded that the gain in PFS of 8.7 months observed with the combination of CRd was considered clinically meaningful and was supported by a clear trend in overall survival benefit, although the data were not mature. The delay in disease progression appeared superior to available alternatives in the setting of relapsed MM at the time of the marketing authorization of carfilzomib. Therefore, given the overall accepted safety profile, which was considered manageable in the current context, the benefit risk for CRd was considered positive.Implications for Practice.Carfilzomib (Kyprolis) was approved in the European Union in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The addition of carfilzomib to lenalidomide and dexamethasone resulted in a clinically meaningful and statistically significant improvement of progression‐free survival compared with lenalidomide and dexamethasone, which was supported by a clear trend in overall survival benefit, although the data were not mature. At the time of the marketing authorization of carfilzomib, the delay in disease progression appeared superior to available alternatives in the setting of relapsed multiple myeloma. In terms of safety, the overall accepted safety profile was considered manageable.

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FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non‐Small Cell Lung Cancer: First‐Line Therapy and Beyond

AbstractOn October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck 95% confidence interval [CI]: 0.41–0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37–0.68; p < .001). In KEYNOTE‐010, patients with disease progression on or after platinum‐containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58–0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49–0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.Implications for Practice.This is the first U.S. Food and Drug Administration approval of a checkpoint inhibitor for first‐line treatment of lung cancer. This approval expands the pembrolizumab indication in second‐line treatment of lung cancer to include all patients with programmed death‐ligand 1‐expressing non‐small cell lung cancer.

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Regarding “Survival Outcomes in Asymptomatic Patients with Normal Conventional Imaging but Raised Carcinoembryonic Antigen Levels in Colorectal Cancer Following Positron Emission Tomography‐Computed Tomography Imaging”

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Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone‐Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single‐Blind, Crossover Phase III Trial

AbstractBackground.To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone‐induced hiccup (DIH) in cancer patients treated with chemotherapy.Materials and Methods.Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups.Results.No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024.Conclusion.Dexamethasone‐induced hiccup is a male‐predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy.Implications for Practice.In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone‐induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.

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Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as the Resected Tumor Has No Ink on It

AbstractBackground.Soft tissue sarcomas (STS) arising in the extremities pose a therapeutic challenge due to concerns of functional morbidity. Resections with negative margins are the mainstay of therapy, but the prognostic significance of surgical margins remains controversial. The purpose of this study was to determine the prognostic impact of surgical margins and clear margin widths in patients with STS of the extremities.Materials and Methods.We assessed the relationship between local recurrence‐free (LRFS), disease‐specific (DSS), and metastasis‐free survival (MFS) and potential prognostic factors retrospectively in a consecutive series of 643 patients treated at our institution between 1996 and 2016. Potential prognostic factors were assessed using univariate and multivariate analyses.Results.The median follow‐up time after primary diagnosis was 5.4 years (95% confidence interval [CI]: 4.8–6.0). The five‐year estimates of the DSS, LRFS, and MFS rates in the entire cohort were 85.3% (95% CI: 81.6–88.3), 65.3% (95% CI: 60.8–69.5) and 78.0% (95% CI: 74.1–81.4), respectively. Histological grade and the quality of surgical margins were independent prognostic factors of all three survival endpoints (LRFS, DSS, MFS) in multivariate analyses. Within the R0 subgroup, univariate and multivariate analyses of categorized (≤1 mm vs. 1–5 mm vs. >5 mm) and non‐categorized margin widths revealed that close and wide negative margins led to similar outcomes. Adjuvant radiation improved local control independently, but not DSS and MFS.Conclusion.Microscopically negative margins were associated with better LRFS, DSS, and MFS regardless of whether adjuvant radiation was applied. Here, surgical margins can be close as long as the resected tumor has no ink on it.Implications for Practice.In the present retrospective analysis of 643 patients with primary soft issue sarcomas of the extremities, surgical margins could be identified as independent predictors of local recurrence‐free, disease‐specific, and metastasis‐free survival. Given the diminished outcome of patients left with positive margins, surgical efforts should aim to achieve microscopically negative margins whenever feasible. It is noteworthy that only the quality of surgical margins, but not the negative margin width attained, had an influence on the prognosis. Our findings suggest that surgical margins can be close as long as the resected tumor has no ink on it.

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Incorporating Tumor Characteristics to the American Joint Committee on Cancer Breast Cancer Staging System

AbstractBackground.The American Joint Committee on Cancer (AJCC) breast cancer staging system provides important prognostic information. The recently published eighth edition incorporates biological markers and recommends the use of a complex "prognostic stage." In this study, we assessed the relationship between stage, breast cancer subtype, grade, and outcome in a large population‐based cohort and evaluated a risk score system incorporating tumor characteristic to the AJCC anatomic staging system.Materials and Methods.Patients diagnosed with primary breast cancer stage I–IV between 2005–2008 were identified in the California Cancer Registry. For patients with stage I–III disease, pathologic stage was recorded. For patients with stage IV disease, clinical stage was utilized. Five‐year breast cancer specific survival (BCSS) and overall survival (OS) rates were determined for each potential tumor size‐node involvement‐metastases (TNM) combination according to breast cancer subtype. A risk score point‐based system using grade, estrogen receptor, and human epidermal growth factor receptor 2 (HER2) status was designed to complement the anatomic AJCC staging system. Survival probabilities between groups were compared using log‐rank test. Cox proportional hazards models were used.Results.Among 43,938 patients, we observed differences in 5‐year BCSS and OS for each TNM combination according to breast cancer subtype. The most favorable outcomes were seen for hormone receptor‐positive tumors followed closely by HER2‐positive tumors, with the worst outcomes observed for triple negative breast cancer. Our risk score system separated patients into four risk groups within each stage category (all p < .05).Conclusion.Our simple risk score system incorporates biological factors into the AJCC anatomic staging system, providing accurate prognostic information.Implications for Practice.This study demonstrates that stage, but also breast cancer subtype and grade, define prognosis in a large population of breast cancer patients. It shows that a point‐based risk score system that incorporates these biological factors provides refined stratification and information on prognosis, improving the anatomic American Joint Committee on Cancer (AJCC) staging system. In addition, the overall mortality and breast cancer specific mortality rates detailed here provide much‐needed information about prognosis in the current era, refining the current AJCC staging.

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Advance Directives, Hospitalization, and Survival Among Advanced Cancer Patients with Delirium Presenting to the Emergency Department: A Prospective Study

AbstractBackground.To improve the management of advanced cancer patients with delirium in an emergency department (ED) setting, we compared outcomes between patients with delirium positively diagnosed by both the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS), or group A (n = 22); by the MDAS only, or group B (n = 22); and by neither CAM nor MDAS, or group C (n = 199).Materials and Methods.In an oncologic ED, we assessed 243 randomly selected advanced cancer patients for delirium using the CAM and the MDAS and for presence of advance directives. Outcomes extracted from patients' medical records included hospital and intensive care unit admission rate and overall survival (OS).Results.Hospitalization rates were 82%, 77%, and 49% for groups A, B, and C, respectively (p = .0013). Intensive care unit rates were 18%, 14%, and 2% for groups A, B, and C, respectively (p = .0004). Percentages with advance directives were 52%, 27%, and 43% for groups A, B, and C, respectively (p = .2247). Median OS was 1.23 months (95% confidence interval [CI] 0.46–3.55) for group A, 4.70 months (95% CI 0.89–7.85) for group B, and 10.45 months (95% CI 7.46–14.82) for group C. Overall survival did not differ significantly between groups A and B (p = .6392), but OS in group C exceeded those of the other groups (p < .0001 each).Conclusion.Delirium assessed by either CAM or MDAS was associated with worse survival and more hospitalization in patients with advanced cancer in an oncologic ED. Many advanced cancer patients with delirium in ED lack advance directives. Delirium should be assessed regularly and should trigger discussion of goals of care and advance directives.Implications for Practice.Delirium is a devastating condition among advanced cancer patients. Early diagnosis in the emergency department (ED) should improve management of this life‐threatening condition. However, delirium is frequently missed by ED clinicians, and the outcome of patients with delirium is unknown. This study finds that delirium assessed by the Confusion Assessment Method or the Memorial Delirium Assessment Scale is associated with poor survival and more hospitalization among advanced cancer patients visiting the ED of a major cancer center, many of whom lack advance directives. Therefore, delirium in ED patients with cancer should trigger discussion about advance directives.

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Neoadjuvant Therapy with Weekly Nanoparticle Albumin‐Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011‐02), a Multicenter, Non‐Randomized, Phase II Trial, with a Companion Biomarker Analysis

AbstractBackground.Nanoparticle albumin‐bound paclitaxel (nab‐Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab‐Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor‐positive (ER+), human epidermal growth factor receptor 2‐negative (HER2‐) disease.Materials and Methods.Women with ER+, HER2‐, stage II–III BC were treated preoperatively with four cycles of weekly nab‐Paclitaxel (150 mg/m2), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.Results.Eighty‐one patients with a median age of 47 years were treated; 64.2% were premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate was 28.4% (95% confidence interval [CI]: 18.6%–38.2%), RCB 0+I (good response) rate was 24.7% (95% CI: 15.3%–34.1%) and RCB 0 (complete response) rate was 7.4% (95% CI: 1.7%–13.1%). Objective response rate by magnetic resonance imaging was 76.5% and rate of conversion to breast conserving surgery was 40.0%. The most frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients, respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3 were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein, acidic, cysteine‐rich (SPARC) overexpression was significantly associated with RCB 0 (odds ratio: 0.079; 95% CI: 0.009–0.689; p = .0216).Conclusion.Despite failing to confirm an RCB III rate ≤16% in nab‐Paclitaxel‐treated patients, the RCB 0+I rate indicates a significant drug antitumor activity with low rates of grade 3–4 toxicity. Our exploratory biomarker analysis suggests a potential predictive role of complete response for SPARC. Confirmatory analyses are warranted, adapting dose and schedule to decrease peripheral neurotoxicity. (Trial registration: European Clinical Trials Database study number: 2011‐004476‐10; ClinicalTrials.gov: NCT01565499).Implications for Practice.The pathological response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle albumin‐bound paclitaxel administered as neoadjuvant treatment for early estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative disease was evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests secreted protein, acidic, cysteine‐rich overexpression in tumor cells as a potential predictor of complete response (RCB 0). Findings point to an encouraging single‐agent neoadjuvant treatment with low toxicity, which warrants future research and development.

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Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents

AbstractTumor lysis syndrome (TLS) is an uncommon but potentially life‐threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B‐cell lymphoma‐2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.Implications for Practice.Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.

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Adipose‐Derived Fatty Acid‐Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients

AbstractBackground.Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose‐derived fatty acid‐binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer.Materials and Methods.We studied 294 women in the oncology department with a family history of breast cancer; 198 of the women had breast cancer, and 96 were healthy controls. The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and high‐sensitivity C‐reactive protein (hsCRP) were determined. We analyzed the association of FABP4 and FABP5 with breast cancer, while adjusting for demographic, anthropometric, and biochemical parameters.Results.Breast cancer patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration of FABP4 and FABP5, respectively. Fatty acid‐binding protein 4 was positively associated with age, body mass index (BMI), FABP5, very‐low‐density lipoprotein cholesterol (VLDLc), non‐high‐density lipoprote in cholesterol (non‐HDLc), Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p < .05), and was negatively associated with HDLc (p < .005) in breast cancer patients. Fatty acid‐binding protein 5 was positively associated with BMI, FABP4, VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP, non‐HDLc, and triglycerides, FABP4 was independently associated with breast cancer (odds ratio [OR]: 1.091 [95% CI: 1.037–1.149]). Moreover, total cholesterol, VLDLc, non‐HDLc, ApoB100, triglycerides, and hsCRP were significantly increased in breast cancer patients (p < .005). In contrast, the non‐esterified fatty acids concentrations were significantly decreased in breast cancer patients (p < .05).Conclusion.Circulating FABP4 and FABP5 levels were increased in breast cancer patients compared with controls. The positive association of FABP4 with breast cancer was maintained after adjusting for important covariates, while the association with FABP5 was lost. Our data reinforce the role of adipose tissue and their adipokines in breast cancer. Despite these data, further studies must be performed to better explain the prognosis or diagnostic value of these blood parameters and their possible role in breast cancer.Implications for Practice.We focus on the effect of adipose tissue on cancer, which is increasingly recognized. The association between adipocyte‐derived adipokines and breast cancer opens new diagnosis and therapy perspectives. In this study, we provide original data concerning FABP4 and FABP5 plasma concentrations in breast cancer patients. Compared to control group, breast cancer patients show higher FABP4 and FABP5 blood levels. Our data suggest that, particularly, circulating FABP4 levels could be considered a new independent breast cancer biomarker. Our work translates basic science data to clinic linking the relationship between adipose tissue and lipid metabolism to breast cancer.

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Are Disagreements in Caregiver and Patient Assessment of Patient Health Associated with Increased Caregiver Burden in Caregivers of Older Adults with Cancer?

AbstractBackground.As patients age, caregivers increasingly provide essential support and patient information. We sought to determine if patient‐caregiver assessments of patient health differ and if differences contribute to burden in caregivers of older adults with cancer.Materials and Methods.One hundred patients, aged ≥65, and their caregivers independently assessed patient function, comorbidity, nutrition, social activity, social support, and mental health. Caregivers completed the Caregiver Strain Index (CSI). Patient‐caregiver assessments were compared using the Wilcoxon signed rank test and paired t test. Association between caregiver burden and differences between patient‐caregiver assessments was examined using generalized linear regression.Results.Median patient age was 70 (range 65–91) and 70% had advanced disease. Sixty percent of patients reported requiring help with instrumental activities of daily living (IADLs); most had good social support (median Medical Outcomes Study [MOS]‐Social Support Survey score 92) and mental health (median Mental Health Inventory score 85).Caregivers were a median age of 66 (range 28–85), 73% female, 68% spousal caregivers, and 79% lived with the patient. Caregivers rated patients as having poorer physical function (more IADLs dependency [p = .008], lower Karnofsky Performance Status [p = .02], lower MOS‐Physical Function [p < .0001]), poorer mental health (p = .0002), and having more social support (p = .03) than patients themselves. Three‐quarters of caregivers experienced some caregiver burden (mean CSI score 3.1). Only differences in patient‐caregiver assessment of the patient's need for help with IADLs were associated with increased caregiver burden (p = .03).Conclusion.Patient‐caregiver assessments of patient function, mental health, and social support differ. However, only differences in assessment of IADLs dependency were associated with increased caregiver burden.Implications for Practice.As patients age, there is a higher incidence of frailty and cognitive impairments. As a result, caregivers play an increasingly vital role in providing information about patient health to healthcare providers, which is used to help healthcare providers tailor treatments and optimize patient health. These findings highlight that caregiver reporting in older adults with cancer may not replace patient reporting in those older adults who are otherwise able to self‐report. Furthermore, clinicians should check for caregiver burden in caregivers who report providing more help with instrumental activities of daily living than patients themselves report and provide appropriate support as needed.

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