Clinical evaluation of macrophages in cancer: role in treatment, modulation and challenges

Abstract

The focus of immunotherapeutics has been placed firmly on anti-tumour T cell responses. Significant progress has been made in the treatment of both local and systemic malignancies, but low response rates and rising toxicities are limiting this approach. Advancements in the understanding of tumour immunology are opening up a new range of therapeutic targets, including immunosuppressive factors in the tumour microenvironment. Macrophages are a heterogeneous group of cells that have roles in innate and adaptive immunity and tissue repair, but become co-opted by tumours to support tumour growth, survival, metastasis and immunosuppression. Macrophages also support tumour resistance to conventional therapy. In preclinical models, interference with macrophage migration, macrophage depletion and macrophage re-education have all been shown to reduce tumour growth and support anti-tumour immune responses. Here we discuss the role of macrophages in prognosis and sensitivity to therapy, while examining the significant progress which has been made in modulating the behaviour of these cells in cancer patients.

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A Narrative Review of the Physical Demands and Injury Incidence in American Football: Application of Current Knowledge and Practices in Workload Management

Abstract

The sport of American football (AmF) exposes athletes to high-velocity movements and frequent collisions during competition and training, placing them at risk of contact and non-contact injury. Due to the combative nature of the game, the majority of injuries are caused by player contact; however, a significant number are also non-contact soft-tissue injuries. The literature suggests that this mechanism of injury can be prevented through workload monitoring and management. The recent introduction of microtechnology into AmF allows practitioners and coaches to quantify the external workload of training and competition to further understand the demands of the sport. Significant workload differences exist between positions during training and competition; coupling this with large differences in anthropometric and physical characteristics between and within positions suggests that the training response and physiological adaptations will be highly individual. Effective athlete monitoring and management allows practitioners and coaches to identify how athletes are coping with the prescribed training load and, subsequently, if they are prepared for competition. Several evidence-based principles exist that can be adapted and applied to AmF and could decrease the risk of injury and optimise athletic performance.

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Die intraoperative Parathormonmessung als bester Indikator einer postoperativen symptomatischen Hypokalzämie

Zusammenfassung

Hintergrund

Das Ziel der Studie ist es, Risikofaktoren für eine passagere postoperative Hypokalzämie (HC) aufzuzeigen und Cut-off-Werte für perioperative Parathormon (PTH)- und Kalziumparameter (Ca) zu bestimmen, um die Morbidität aufgrund einer symptomatischen HC zu vermindern.

Material und Methoden

Am Luzerner Kantonsspital wurden im Rahmen einer retrospektiven Studie zwischen 2006 und 2013 insgesamt 353 Patienten hinsichtlich des Risikos einer HC nach totaler Thyreoidektomie statistisch ausgewertet. Zu definierten Zeitpunkten wurden die Laborwerte für Kalzium und PTH im Serum bestimmt.

Ergebnisse

Die Prävalenz der postoperativen laborchemischen HC lag bei 43 %. Eine symptomatische HC entwickelten 10 % der Patienten. Signifikante Risikofaktoren einer laborchemischen und symptomatischen HC waren hierbei die Kalziumwerte (prä-, intra, 4 h und 1 Tag postoperativ), die PTH-Werte (intraoperativ, 4 h und 1 Tag postoperativ) sowie der PTH-Abfall. Die PTH-Werte präoperativ, das Alter der Patienten, das Gewicht der Schilddrüse, die Diagnose sowie das Geschlecht stellten keine signifikanten Risikofaktoren dar. In der ROC-Analyse („receiver operating characteristics") zeigte die Kalziummessung 4 h postoperativ die beste Vorhersagekraft bzgl. laborchemischer HC, wohingegen die PTH-Messung intraoperativ am aussägekräftigsten bzgl. der symptomatischen HC war.

Schlussfolgerung

Sowohl Kalzium‑/PTH-Werte als auch ein Abfall der PTH-Werte im Verlauf sind signifikante Risikofaktoren einer postoperativen HC. Präoperativ ist nur die Kalziummessung prognostisch signifikant. Die intraoperative PTH-Messung ist im klinischen Setting der sinnvollste und sensitivste Faktor, um eine postoperative passagere HC frühzeitig zu erkennen.

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Frequent oncogenic BRAF V600E mutation in odontogenic keratocyst

Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Yong Hoon Cha, Eunae Sandra Cho, Hee Eun Kang, Jaemin Ko, Woong Nam, Hyung Jun Kim, Nam Hee Kim, Hyun Sil Kim, In-Ho Cha, Jong In Yook
ObjectivesOdontogenic keratocyst (OKC), also known as keratocystic odontogenic tumor (KCOT), has clinical significance due to its high incidence as well as high recurrence rate after surgical enucleation. Current clinical management for OCK is entirely dependent on surgical approach. While various genetic alterations, such as PTCH1 mutation and loss of heterozygosity in tumor suppressor genes, have been reported, the molecular background of OKC is not well-understood. Although recent identification of BRAF V600E mutation and subsequent activation of mitogen-activated protein kinase (MAPK) pathway in ameloblastoma and odontogenic tumors provide additional options with targeted therapeutics, the molecular background of OKC is not well understood.Materials and methodsIn this study, we examined BRAF V600E mutation from paraffin embedded OKC samples by tumor cell enriched microdissection and TA cloning of amplified DNA. We further examined the relationship between BRAF V600E mutation and clinical parameters.ResultsWe found frequent BRAF V600E mutation in OKC (24 of 38 samples, 63.2%). However, BRAF V600E mutational status is not related with clinical indexes such as size, location, and recurrence. In orthokeratinized odontogenic cyst, there is one case of BRAF 600E mutation from 11 samples (9.1%).ConclusionThese results indicate that BRAF V600E mutation occurs in OKCs at a high rate and plays an important role in the pathogenesis of OKCs.



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PRAS40 promotes NF-κB transcriptional activity through association with p65

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TNFα-YAP/p65-HK2 axis mediates breast cancer cell migration

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Xanthine dehydrogenase downregulation promotes TGFβ signaling and cancer stem cell-related gene expression in hepatocellular carcinoma

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Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes

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PulmCrit: Large-bore suction for intubation: strategies & devices

The ideal suction tool for intubations is debatable, but it seems clear that the Yankauer is a poor choice.  Persistent use of the Yankauer suction catheter for airway management represents a profession-wide failure in our ability to manage large-volume regurgitation.

EMCrit by Josh Farkas.

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P-AzeFlu provides rapid and effective allergic rhinitis control: results of a non-interventional study in Romania.

P-AzeFlu provides rapid and effective allergic rhinitis control: results of a non-interventional study in Romania.

Rhinology. 2017 Sep 24;:

Authors: Agache I, Doros IC, Leru PM, Bucur I, Poenaru M, Sarafoleanu C

Abstract
BACKGROUND: Allergic Rhinitis and its Impact on Asthma (ARIA) and the European Union (EU) recommend a shift to guide allergic rhinitis (AR) treatment decisions from symptom severity to disease control, using a simple visual analogue scale (VAS). Using this VAS we assessed, in a real-life study in Romania, the effectiveness of MP-AzeFlu nasal spray.
METHODOLOGY: In this multi-centre, prospective, non-interventional study, 253 patients (over 11 years old) with moderate-to-severe AR were prescribed MP-AzeFlu and assessed their symptoms on a VAS (0 (not at all bothersome) to 100 mm (very bothersome)) on Days 0, 1, 3, 7 and 14. The proportion of patients who achieved a defined VAS score cut-off for well-controlled (38 mm) AR were also calculated. Patients perception of disease control was assessed on Day 3.
RESULTS: MP-AzeFlu use was associated with a mean (standard deviation) VAS score reduction from 78.4 (15.1) mm at baseline to 14.7 (15.1) mm on the last day. Effectiveness was consistent irrespective of disease severity, phenotype or patient age. 83.4% of patients achieved the smaller than 39 mm well-controlled VAS score cut-off by last day and 95.2% considered their symptoms to be well- or partly controlled at Day 3.
CONCLUSIONS: MP-AzeFlu provided rapid, effective and sustained AR symptom control in a real-life setting in Romania, irrespective of severity, phenotype or patient age, aligning with ARIA and EU recommendations and supporting the position of MP-AzeFlu as the drug of choice for the treatment of moderate-to-severe AR.

PMID: 28942457 [PubMed - as supplied by publisher]

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HPV-E6 protein enriches the CD55(+) population in cervical cancer cells promoting radio-resistance and cancer aggressiveness

Abstract

Accumulating evidence indicates that the human papilloma virus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Sub-populations of cells that reside within tumors are responsible for tumor resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified. Here, we isolated sphere-forming cells, which exhibited self-renewal ability, from primary cervical tumors. Gene expression profiling revealed that CD55 was upregulated in primary cervical cancer sphere cells. Flow cytometric analysis detected abundant CD55(+) populations among a panel of HPV-positive cervical cancer cell lines, while only few CD55(+) cells were found in HPV-negative cervical cancer and normal cervical epithelial cell lines. The isolated CD55(+) sub-population from the C33A cell line exhibited significant sphere-forming ability and enhanced tumorigenicity, cell migration and radio-resistance. In contrast, the suppression of CD55 in HPV-positive CaSki cells inhibited tumorigenicity both in vitro and in vivo and sensitized cells to irradiation treatment. In addition, ectopic expression of HPV-E6 in HPV-negative cervical cancer cells dramatically enriched the CD55(+) sub-population. CRISPR/Cas9 knockout of the CD55 gene in an HPV-E6-overexpressing stable clone abolished the tumorigenic properties exerted by HPV-E6. Taken together, our data suggest that HPV-E6 protein expression enriches the CD55(+) population, which contributes to tumorigenicity and radio-resistance in cervical cancer cells. Targeting CD55 via CRISPR/Cas9 may represent a novel avenue for developing new strategies and effective therapies for the treatment of cervical cancer.

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Spatial relationships of the bronchial arteries to the left recurrent laryngeal nerve in the sub-aortic arch area

Abstract

Purpose

To safely perform lymphadenectomy in the sub-aortic arch area during esophagectomy for esophageal cancer, we investigated the spatial relationships between the bronchial arteries (BAs) and the left recurrent laryngeal nerve (LRLN).

Methods

For this macro-anatomical study, 72 cadavers were used.

Results

Of the 195 dissected BAs, 15 (7.7%) arteries ran dorsally across the LRLN. Such a running pattern of the BA was found in 15 (20.8%) of the 72 cadavers. Fourteen (93.3%) of the 15 arteries ran anteriorly along the left side of the esophagus, and 13 (86.7%) passed further to the lateral side of the left main bronchus to reach the ventral surface of the tracheobronchus; we named this running pattern "Type III". Of the 51 arteries with the Type III pattern, 25.5% ran across the dorsal side of the LRLN.

Conclusion

Approximately 20% of the cadavers had BAs running dorsally to the LRLN in the sub-aortic arch area. Most of these arteries had the Type III pattern. One-quarter of the BAs with the Type III pattern showed this running pattern. Care must be practiced to safely perform lymphadenectomy for esophageal cancer in patients with Type III BAs.

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Short-term outcomes of laparoscopic surgery in octogenarians with colorectal cancer: a single-institution analysis

Abstract

Purpose

The number of elderly patients with colorectal cancer (CRC) treated with surgery has gradually increased. The aim of this study was to evaluate the short-term outcomes in patients ≥80 years of age who underwent laparoscopic or open surgery for CRC using a propensity score-matched analysis to make uniform the patient background characteristics affecting the postoperative morbidity and mortality.

Methods

We compared the short-term outcomes of open vs. laparoscopic surgery in patients with CRC ≥80 years of age between 2010 and 2015. Fifty-two patients undergoing laparoscopic colectomy for CRC were matched to 52 patients undergoing open colectomy with respect to gender, age, body mass index, performance status, prognostic nutritional index, Charlson Comorbidity Index score, tumor-node-metastasis stage, and tumor location. The operative time, blood loss, length of hospital stay, and postoperative complications were investigated.

Results

Blood loss was less during laparoscopic surgery than during open surgery (40 vs. 140 ml, p < 0.001). In the laparoscopic surgery group, the hospital stay was shorter (11 vs. 14 days, p < 0.001) and the morbidity rate lower (21.2 vs. 40.4%) than in the open surgery group. The mortality for both groups was similar (0 vs. 1.9% for laparoscopic surgery vs. open surgery).

Conclusion

Laparoscopic surgery in octogenarians with CRC is a safe, low-invasive alternative to open surgery with less blood loss and a shorter hospital stay.

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Modifiable and non-modifiable risk factors for surgical site infection after colorectal surgery: a single-center experience

Abstract

Purpose

Surgical site infection (SSI) is the most common complication of colorectal surgery, resulting in significant burden in terms of morbidity and length of hospital stay. The aims of this study were to establish the incidence of SSI in patients undergoing colorectal surgeries and to identify potentially modifiable risk factors to reduce overall SSI rates.

Methods

This retrospective study analyzed patients who underwent colorectal resection at our Department. Patients were identified using a prospective SSI database. Univariate and multivariate analyses were used to identify risk factors.

Results

A total of 687 patients were enrolled in the study and the overall SSI rate was 19.9% (137 patients). Superficial incisional surgical site infections (SSSIs) developed in 52 (7.6%) patients, deep incisional surgical site infections (DSSIs) developed in 15 (2.2%), and organ/space infections (OSIs) developed in 70 (10.1%). Univariate and multivariate analyses confirmed that age, diabetes, emergency surgery, and a high infection risk index are risk factors for SSI.

Conclusions

There are some modifiable and non-modifiable risk factors for SSI. IRI and age are non-modifiable, whereas the timing of surgery and diabetes can be modulated by trying to defer some emergency procedures to elective ones and normalizing the glycemia of diabetic patients.

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The eye as a complement dysregulation hotspot

Abstract

Complement turnover is tightly regulated throughout the human body in order to prevent over-activation and subsequent damage from inflammation. In the eye, low-level complement activation is maintained to provide immune tolerance in this immune privileged organ. Conversely, the complement system is suppressed in the cornea to protect it from continuous immunological insult. Over-activation of the complement cascade has been implicated in the disease progression of glaucoma and diabetic retinopathy and is now known to be a central driver in the pathogenesis of age-related macular degeneration (AMD). Indeed, it is with AMD where the most recent and exciting work has been carried out with complement-based therapies entering into clinical trials. However, the success of these trials will depend upon delivering the therapeutics to the correct anatomical sites within the eye, so a full understanding of how complement regulation is compartmentalized in the eye is required, a topic that will be highlighted in this review.

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Sporadic Retroperitoneal Fibrosis: a Gentle Giant

Abstract

Fibromatosis covers a broad spectrum of benign fibrous tissue proliferation and is characterized by slow growing, locally infiltrative growth pattern with a high propensity for local recurrence. We report on a case of multicentric fibromatosis originating from the retroperitoneal space and submandibular triangle, in an 18-year-old lady. Computed tomography revealed a retroperitoneal abdominopelvic tumor extending from the left sub-diaphragmatic space to the pelvic inlet which had enveloped the solid viscera in the left upper quadrant with a displaced celiac axis. She also had a recurrent resectable fibromatosis in left submandibular gland. Histopathological evaluation revealed fibromatosis. Preoperatively, Vinblastin-, Methotrexate-, Tamoxifen-based systemic chemotherapy was offered for 12 weeks in an attempt to downsize the mass. An en bloc complete resection of tumor with multi-visceral resection was performed to achieve negative margins and since then, the patient has remained asymptomatic without any signs of tumor recurrence during the 12th month follow-up visit. Complete resection with negative margins is the treatment of choice and majority of the lesions are amenable for surgical resections. Adjuvant therapy using non-steroidal anti-inflammatory agents, tamoxifen, interferon, anti-neoplastic agents, and radiotherapy, either alone or in combination finds application for un-resectable or recurrent cases.

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Cancers, Vol. 9, Pages 130: Alcohol and Hepatocellular Carcinoma: Adding Fuel to the Flame

Cancers, Vol. 9, Pages 130: Alcohol and Hepatocellular Carcinoma: Adding Fuel to the Flame

Cancers doi: 10.3390/cancers9100130

Authors: Pierluigi Ramadori Francisco Cubero Christian Liedtke Christian Trautwein Yulia Nevzorova

Primary tumors of the liver represent the fifth most common type of cancer in the world and the third leading cause of cancer-related death. Case-control studies from different countries report that chronic ethanol consumption is associated with an approximately 2-fold increased odds ratio for hepatocellular carcinoma (HCC). Despite the substantial epidemiologic data in humans demonstrating that chronic alcohol consumption is a major risk factor for HCC development, the pathways causing alcohol-induced liver cancer are poorly understood. In this overview, we summarize the epidemiological evidence for the association between alcohol and liver cancer, review the genetic, oncogenic, and epigenetic factors that drive HCC development synergistically with ethanol intake and discuss the essential molecular and metabolic pathways involved in alcohol-induced liver tumorigenesis.

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Polarized transilluminating dermoscopy: Bedside trichoscopic diagnosis of trichothiodystrophy

Abstract

Trichothiodystrophy is a rare autosomal recessive disorder resulting in a broad range of systemic abnormalities. Polarizing microscopy of the hair reveals the pathognomic "tiger tail" of alternating light and dark bands, but the need for a microscope prevents rapid bedside diagnosis. We describe a new technique for the bedside diagnosis of trichothiodystrophy using a handheld polarizing dermatoscope, precluding the need for microscopic examination.

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Self-limited neonatal periumbilical erythema

Abstract

We report three cases of neonatal, noninfectious, periumbilical erythema that resolved shortly after umbilical stump detachment. We hypothesize that these infants experienced an inflammatory and vasodilatory response during the normal umbilical cord separation process. We propose a new term: self-limited neonatal periumbilical erythema.

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Comparison of psoriasis and atopic dermatitis guidelines—an argument for aggressive atopic dermatitis management

Abstract

The development of effective systemic treatments has revolutionized the treatment of inflammatory skin diseases. The availability of safe new treatments and the understanding of psoriasis as a systemic disease with comorbidities and effects on quality of life have driven the current aggressive treatment paradigm of psoriasis. Historically the morbidity of atopic dermatitis (AD) has been dismissed, given the perception of AD as "just" a rash. Differences in the guidelines for psoriasis and AD management may suggest variations in the current conceptualization of disease severity and effects on quality of life. Published guidelines from the American Academy of Dermatology for the management of psoriasis and AD were reviewed. We recorded the similarities and differences in disease assessment and therapy. The threshold to use biologic agents for moderate to severe psoriasis highlights the aggressive nature of modern psoriasis treatment. AD guidelines include an assessment of quality of life but do not designate a disease severity threshold for systemic treatment. AD and psoriasis have a tremendous effect on quality of life. The AD guidelines have a less aggressive approach to disease management than the psoriasis guidelines. We should think critically about rapid advancement to systemic agents in AD management, especially now that more and better agents are being developed.

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