OtoRhinoLaryngology News: 03/22/18

Πέμπτη 22 Μαρτίου 2018

Local Anesthetic Injection Speed and Common Peroneal Nerve Block Duration: A Randomized Controlled Trial in Healthy Volunteers

Background and Objectives The speed of local anesthetic (LA) injections in peripheral regional anesthesia ranges from slow continuous infusions (3–12 mL/h) to rapid manual injections (>7500 mL/h). Optimizing injection speed could augment the spread of LA toward the targeted nerves and influence nerve block characteristics. The objective of this study was to investigate whether injection speed of a single dose of LA affects peripheral nerve block duration. Methods After approval from the Danish Regional Scientific Ethics Committee, we enrolled 60 healthy adult volunteers. We used an ultrasound-guided catheter-based technique to perform a common peroneal nerve block. Participants were randomized to receive 4.0 mL of ropivacaine 0.2% with 1 of 5 injection speeds: 12, 60, 300, 600, or 1800 mL/h. Investigators and participants were blinded to group assignment and intervention. Primary outcome was duration of sensory nerve block defined by insensitivity toward cold. Secondary outcomes were duration of motor nerve block, time to onset of sensory nerve block, and grades of sensory and motor nerve block. Intergroup differences were tested by one-way analysis of variance. Results We found no differences in sensory block duration between the 5 groups. Durations were median [range]: 11 [6–14], 12 [9–14], 10.5 [2–15], 11 [8–17], and 12 [9–18] hours, respectively (P = 0.294). In addition, we found no differences in secondary outcomes. Conclusions Injection speed of LA in the range of 12 to 1800 mL/h did not affect common peroneal nerve block duration. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02801799. Accepted for publication November 13, 2017. Address correspondence to: Mikkel Herold Madsen, MD, Department of Anesthesiology, Nordsjællands Hospital Hillerød, Dyrehavevej 29, Building 52B, 4th Floor, DK-3400 Hillerød, Denmark (e-mail: mhmadsen@gmail.com). This work was funded by Innovation Fund Denmark and by Nordsjællands Hospital Hillerød. This work was presented in part at the American Society of Regional Anesthesia and Pain Medicine 42nd Annual Regional Anesthesiology and Pain Medicine Meeting; San Francisco, CA; April 6 to 8, 2017. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Percutaneous Screws and External Fixation in Frontal Sinus Anterior Wall Fractures

Fractures of the frontal sinus are frequently encountered injuries of maxillofacial fractures. The most common causes are traffic accidents, followed by sports-related injuries. There is still no consensus regarding the optimal management of frontal sinus fractures. The authors report a patient with depressed anterior wall fracture of the frontal sinus and superior orbital rim fracture. Reduction was performed by traction from 2 screws applied percutaneously to the depressed fragments and external fixation with an aluminum nasal splint. This technique is both minimally invasive and permits easy fixation in suitable patients. Address correspondence and reprint requests to Muhammet Uraloğlu, MD, Karadeniz Teknik Üniversitesi Tip Fakültesi, Farabi Hastanesi Plastik Cerrahi Anabilim Dali, Trabzon, Turkey; E-mail: uraloglu@hotmail.com Received 2 November, 2017 Accepted 4 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Active Intracystic Negative Pressure Could Induce Osteogenesis

Based on previous findings, the author introduces the term "sugosteogenesis," a biological phenomenon that occurs by using the Evocyst, a device that exerts active intracystic negative pressure. The term "sugosteogenesis" comes from the Latin word "sugo-," meaning "suck," and Greek words "osteo-," meaning "bone," and genesis, "origin." Address correspondence and reprint requests to Dr Jaime Castro-Núñez, Division of Oral and Maxillofacial Surgery, College of Dentistry, University of Kentucky, 800 Rose Street, Lexington, KY 40536; E-mail: jaime.castro@uky.edu Received 21 October, 2017 Accepted 20 December, 2017 The authors report no conflicts of interest © 2018 by Mutaz B. Habal, MD.

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Surgical Treatment of Nonsyndromic Unicoronal Craniosynostosis

Purpose: Unicoronal synostosis (UCS) remains one of the most difficult craniofacial conditions to treat. This review attempts to consolidate all existing literature from the past 25 years that has investigated surgical treatment of nonsyndromic UCS. Additional attention is paid to specific areas of controversy regarding surgical management and evaluation of UCS: outcomes of fronto-orbital advancement (FOA) versus endoscopic strip craniectomy (ESC), emergence of spring-associated cranioplasty for craniosynostosis, and morphologic assessment metrics. Methods: A literature search from 1992 to 2017 was performed with a defined search strategy and manual screening process. About 24 studies were included in the final review. Results: There is inconsistency among studies in measuring outcomes. Despite wide utilization, FOA produces mixed results, especially when looking at long-term outcomes. Preliminary data suggest advantages to using ESC over FOA with regard to facial symmetry, postoperative strabismus, and operating time. Distraction osteogenesis has long been utilized in Asia and is now being actively studied in the United States. Data on spring-assisted cranioplasty are lacking. Long-term results at skeletal maturity for many of these techniques are lacking. Discussion: Despite some promising results, methods of measurement are inconsistent and long-term data are lacking. All future research in this area would benefit from consistent and standardized reporting of data, including perioperative statistics and reproducible 3-dimensional computed tomography craniofacial measurements. Additionally, no definitive recommendations can be made until data at skeletal maturity are studied, and all studies would benefit from long-term follow-up data. Address correspondence and reprint requests to Jake Alford, BS, UT Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390; E-mail: Jake.alford@utsouthwestern.edu Received 29 November, 2017 Accepted 4 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Cystic Progression of a Cavernous Malformation at the Level of the Trigeminal Root Entry Zone Presenting With Sudden Onset of Trigeminal Neuralgia

Background: Cavernous malformations (CM) in the cerebellopontine angle (CPA) are rare, and most of them are solid and extend from the internal auditory canal into the CPA. In contrast, cystic CM arising in the CPA and not involving the internal auditory canal and dura of the skull base are extremely rare. The authors present an uncommon large cystic progression of a cavernous malformation at the level of the trigeminal root entry zone evolving to severe trigeminal neuralgia and brainstem compression. Methods: A 62-year-old female presented a sudden onset of left trigeminal neuralgia, caused by a large cystic lesion at the level of the root entry zone of the left 5th nerve. On neurological examination, she showed slight gait ataxia and hypoesthesia on the left hemiface (on the first and second trigeminal branches). Other cranial nerves were in order. Magnetic resonance imaging showed a large cystic intracranial mass, with a small solid portion, leading to brainstem compression. Results: Microsurgical removal of the lesion was performed via retrosigmoid approach, with intraoperative monitoring of somato-sensory evoked potentials, facial, and cochlear nerves. The posterior-medial portion of the lesion was solid, whereas the main portion was cystic, containing xanthochromic fluid. The small solid lesion continued with a thin capsule of a large cyst adherent to brainstem, cerebellar hemisphere, and trigeminal nerve entry zone. A big draining vein arising from the solid part of the lesion runned parallel to brainstem. The mass was piecemeal totally removed. After surgery the patient recovered both left trigeminal neuralgia and hypoesthesia; ataxia was significantly relieved too. Postoperative magnetic resonance imaging confirmed the total removal. Histopathological features were consistent with a CM. At 6-month follow-up, patient's symptoms at the presentation had resolved. Conclusion: The authors present a very rare patient of large cystic cavernous malformation at the level of the trigeminal root entry zone presenting with sudden onset of trigeminal neuralgia. Even if it has not established imaging features, a cystic cavernoma of the cerebello-pontine angle may be suspected when a cystic mass is present, not involving the internal acoustic meatus nor the skull base dura mater. Careful microneurosurgical technique and monitoring of cranial nerves allow good long-term results. Address correspondence and reprint requests to Luciano Mastronardi, MD, PhD, San Filippo Neri Hospital, Via Reno 14, 00198 Rome, Italy; E-mail: mastro@tin.it Received 3 December, 2017 Accepted 2 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Stranger Things: A Whimsical Account of a Demineralized Bone Matrix Study With Unexpected Results

No abstract available

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Evaluation of Fibrin Clot Attachment on Titanium Laser-Conditioned Surface Using Scanning Electron Microscopy

Objectives: The study aimed to evaluate the effects of different titanium surface treatments on blood clot extension (bce). Methods: A total of 54 titanium disks with machined surface (M), laser-conditioned surface (L), and grit-blasted surface (S) were used in the present study. The surface characteristics such as contact angles and the microroughness were determined on each group (n = 4). To evaluate the bce, 0.1 mL of human blood was dropped onto the surface of each specimen and left for 7 minutes at room temperature. After fixation, dehydration, and gold sputtering treatments, the specimens were observed under scanning electron microscope. The bce values were expressed as percentage of specimen surface covered by blood clot. Results: The surface roughness (Ra ± standard deviation [SD]) was 0.75 ± 0.02 μm for M, 0.25 ± 0.02 μm for L, and 1.30 ± 0.03 μm for S. The contact angles measured in static conditions (WCA ± SD) were 71 ± 5.4° for M, 107 ± 6.6° for L, and 91 ± 7.2° for S. Regarding the bce (bce ± SD) of M samples (65.5 ± 4.3%) was statistically lower compared with both L (83.4 ± 5.1%) and S samples (72.4 ± 4.7%) (P

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Allotransplantation: From Dream to Reality

No abstract available

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Review of “Prevalence of Needlestick Injuries, Attitude Changes, and Prevention Practices Over 12 Years in an Urban Academic Hospital Surgery Department” by Hasak JM, Novak CB, Patterson JMM, Mackinnon SE in Ann Surg 267: 291–296, 2018

No abstract available

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Treatment of an Uncommon High-Pressure Orbital Injection Injury

Injection injuries occur most commonly in the hand and digits; however, there are a limited number of reports in the literature describing injection injuries involving the orbit. High-pressure orbital injection injuries pose a number of unique challenges to the treating physician, and the approach to treating these injuries remains controversial. Often times, the extent of tissue damage is not fully appreciated at presentation, which may lead to missed diagnoses or inadequate initial treatment. In this study, the authors describe a rare incidence of high-pressure orbital injection injury. A 19-year-old male presented to the emergency department after injection of his left orbit with oil-based paint. Worsening clinical symptoms and increasing intraocular pressures within the first 24 hours necessitated take back to the operating room for orbital decompression and debridement. After an initial improvement in symptoms, the patient's clinical status deteriorated again, requiring further orbital decompression and additional periorbital debridement. Two weeks after initial presentation, soft tissue reconstruction of the surgical wounds was performed with full thickness skin grafts. The patient's globe and vision were both preserved. Orbital injection injuries, though rare, are potential globe threatening injuries. Physicians should have a low threshold for intervention and patient's must be observed closely over the first 72 hours after injury. Early diagnosis, prompt debridement, and a multidisciplinary approach are keys to improving patient outcomes. Address correspondence and reprint requests to Matthew P. Fahrenkopf, MD, 221 Michigan St NE, Suite 402, Grand Rapids, MI 49503; E-mail: matt.fahrenkopf@gmail.com Received 2 January, 2018 Accepted 8 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Novel Application of Ultrasonic Bone Aspirator for Hump Nose

Objective: This study was conducted to introduce and evaluate the efficacy of an ultrasonic bony aspirator in rhinoplasty for hump removal. Design: Retrospective study. Setting: University medical center. Patients: Twenty patients who underwent hump removal using an ultrasonic bone aspirator from October 2013 to November 2016 were enrolled in the study. Main Outcome Measures: Patients were followed for >3 months after surgery. External nose status and surgical results were investigated using photographs. Postoperative complications were evaluated. Results: Of the 30 patients enrolled in this study, 11 were females and 19 were males. Preoperative nasal deformities of all patients were characterized as bony humps. Postoperative dorsal status was significantly improved. There were no obvious complications such as over or under correction, delayed healing, infection, soft tissue injury, or deformity of the nasal dorsum. Conclusion: Application of an ultrasonic bone aspirator to remove humps in rhinoplasty is easy, safe, and effective. Address correspondence and reprint requests to Jae Hwan Kwon, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, 34 Amnam-dong, Seo-gu, Busan 602-702, Korea; E-mail: entkwon@hanmail.net Received 23 October, 2017 Accepted 9 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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An Unusual Case of Headache: Isolated Fungus Ball in Concha Bullosa

A concha bullosa forms when the middle turbinate becomes pneumatized, which is a common anatomic variation; however, fungus ball in concha bullosa is rather rare. An otherwise healthy 52-year-old man presented to our ear, nose and throat clinic with the complaints of midfacial pressure headache and malodorous postnasal drip. Computed tomography of the paranasal sinuses demonstrated a polypoid hyperdense lesion with slight microcalcifications in the right nasal cavity, accompanied with a complicated fluid collection in the right frontoethmoideal recess seen as hypodensity in contrast to this hyperdensity. The histopathological examination reported a fungal infection. We present an extremely rare case of isolated fungal mass in the right middle concha detected in an early stage without any evidence of fungal infection of the other paranasal sinuses and discuss the importance of reevaluation of the computed tomography scans in suspicion of a fungal sinusitis. Correspondence to Kadir Cagdas Kazikdas, MD, Department of Otorhinolaryngology, Near East University Faculty of Medicine, Near East Blv, 99138 Nicosia, Cyprus; E-mail: ckazikdas@gmail.com Received 25 October, 2017 Accepted 9 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Accessory Submandibular Salivary Gland Forming a “Horseshoe” With the Main Submandibular Salivary Gland: A Unique Variation

Presence of accessory submandibular salivary gland (ASSG) is an extremely rare variation. Knowledge of its relations could be very useful to oral and maxillofacial surgeons, head and neck surgeons, and radiologists. During dissection classes, an ASSG was noted between the mylohyoid and hyoglossus muscles. The main submandibular salivary gland had superficial and deep parts. The deep part was narrow and measured about 5 cm. The lingual nerve passed between the superficial and deep parts. The accessory submandibular gland was situated below and parallel to the deep part of SSG. It also measured 5 cm. The ASSG had its own duct, which joined the duct of main gland. The ASSG and the deep part of the SSG were united at the lateral border of geniohyoid muscle to give a characteristic "horseshoe" appearance. The ASSG overlapped both lingual and hypoglossal nerves. Address correspondence and reprint requests to Satheesha B. Nayak, PhD, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Madhav Nagar, Manipal, Udupi576104, Karnataka, India; E-mail: nayaksathish@gmail.com Received 16 November, 2017 Accepted 11 February, 2018 The author reports no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Zygomaticofacial, Zygomaticoorbital, and Zygomaticotemporal Foramina

This study aimed to assess the anatomical and morphometric characteristics of the main zygomaticofacial (ZFF), zygomaticoorbital (ZOF), and zygomaticotemporal (ZTF) foramina in Brazilian dry skulls. 61, 69, and 42 skulls for ZFF, ZOF, and ZTF were evaluated by a single calibrated examiner for format, transverse and vertical diameters, and distances from the foramina to anatomical landmarks. Paired t test, Wilcoxon test, Pearson and Spearman correlations were used. Circular outline was the predominant format for ZFF and ZTF, while oval format was the most frequent for ZOF. Median distances from ZFF to frontozygomatic and zygomaticomaxillary sutures were higher on right and left sides of the skulls, respectively (P 0.05). No significant difference was found for distance from the ZTF to zygomatic arch between sides (P > 0.05), although there was a positive correlation (P

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Surgical Treatment of Rhinosinusitis-Related Orbital Complications: Factors Affecting Irreversible Blindness

If left untreated, rhinosinusitis can rarely cause a devastating complication irreversible blindness (IB). Despite new technologies in endoscopic sinus surgery and use of new broad-spectrum antibiotics, IB outcome is still a problem for surgically treated orbital complication of paranasal sinus infection (OCPSI) patients, and factors leading to IB outcome are not actually known. The aim of this study was to assess the factors leading to the IB outcome for surgically treated OCPSI patients. Results of 25 surgically treated OCPSI patients in our clinic were combined with surgically treated OCPSI patients reported through the PubMed database search from the year 2007. Patients were divided into 2 groups: IB group and recovery group. Patients having at least 1 immune status-related additional risk factor (ARF) were more common in the IB group, having an at least 1 ARF had 1.683 risk value of IB outcome (RR: 1.683, P = 0.006). IB patients had statistically significant higher mean (21.87 ± 40.35, P = 0.005) time interval (days) (TI) between onset of ophthalmological symptoms and surgical intervention compared to recovery group patients (2.92 ± 2.53). ROC curve analysis for an estimation of IB outcome according to the TI value demonstrated that a cut-off value of ≥2.5 days had the ideal sensitivity (87.5%) and specificity (71.9%) that resulted in IB outcome. (80.5% power, P = 0.008) IB and recovery group patients did not differ according to orbital complication type according to Chandler's classification (P = 0.492) and white blood cell count status (P = 0.584). In conclusion, OCPSI patients with ARFs and delayed admission after onset of orbital symptoms have a higher risk of IB outcome. These patients deserve prompt evaluation and early surgical intervention to prevent blindness. With future studies, new surgical criteria, including the ARF status and onset of ophthalmological symptoms (≥2.5 days) may be added to classical surgical criteria to prevent IB for OCPSI cases. Address correspondence and reprint requests to Onur Ismi, MD, Mersin Üniversitesi Tip Fakültesi Hastanesi, Kulak Burun Boğaz A.D Çiftlikköy Kampüsü, Çiftlikköy/Yenişehir-Mersin/Turkey; E-mail: dronurismi@gmail.com. Received 9 January, 2018 Accepted 9 February, 2018 Surgical outcomes of the first 20 patients of this manuscript was presented as oral presentation at the 38th National Turkish Otorhinolaryngology Head Neck Surgery Congress. The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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The “Flap Suture Anchoring” Technique for Safe Oral Floor Reconstruction With Preservation of Alveolar Process

Flaps-based microsurgery is routinely applied to reconstruct oral floor defects caused by oncologic resection. To prevent orocutaneous fistulae, flaps are frequently sutured with buccal vestibule mucosa after sacrificing the alveolar process. The patients suffered denture loss and irreversible structural damage. For reliable oral floor reconstruction with preservation of alveolar process, the authors introduced the flap "suture anchoring" technique. Oral floor, hemiglossal-oral floor, and tongue base-parapharyngeal wall-oral floor defects were included in this study. The flap anchoring technique involves structural oral floor reconstruction with a chimeric anterolateral thigh-free flap or radial forearm flap with adipofascial tissue extension. The dead space in oral floor is filled with vastus lateralis muscle or adipofascial tissue, then holes are drilled on the alveolar bone among tooth root, beneath the attached gingiva. Skin paddle is sutured with 4-0 sutures through the alveolar holes thus anchored to the mandible. By applying this technique, there was no wound infection or orocutaneous fistulae in all patients postoperatively, even experienced postoperative radiotherapy. In addition, a soft and natural jaw-tongue furrow could be formed to allow the free movement of tongue. Taken together, the flap anchoring technique offers a safe and reliable approach to recover oral function and preservation of occlusion. Address correspondence and reprint requests to Wei Wu, MD, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; E-mail: wuweidds@126.com Received 14 January, 2018 Accepted 9 February, 2018 This work was supported by the National Natural Science Foundation of China (grant numbers 31370997 and 81422008); the National High-tech R&D Program of China, and 863 Program (grant number 2015AA020920). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Simultaneous Implant Placement in a Mandibular Defect Reconstructed With a Free Fibula Graft and Fabrication of a Fixed Metal Porcelain Prosthesis

This clinical report presents the multidisciplinary treatment approach for a 23-year-old male patient who underwent a total mandibular reconstruction due to trauma in the past and experienced postoperative complications. For his retreatment, exposed fixation plate was removed and infected bone was debrided and then a free fibula graft augmentation with simultaneous implant placement procedure was performed. After an osseointegration period of 6 months, a screw-retained porcelain fused to metal fixed prosthesis was fabricated and delivered. Address correspondence and reprint requests to Banu Karayazgan-Saraçoğlu, DDS, PhD, Okan University, Tuzla Campus, 34959 Akfirat-Tuzla, Istanbul, Turkey; E-mail: bkyazgan@gmail.com Received 21 January, 2018 Accepted 13 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Endoscopic Transsphenoidal Surgery for an Adult Patient With Giant Exophytic Chiasmatic/Hypothalamic Glioma

Optic pathway hypothalamic gliomas are intrinsic low-grade gliomas involving the optic nerve, chiasm, optic tract, and hypothalamus. The rarity of these tumors and their unpredictable course make assessment and standardization of treatment modalities difficult. Tumor debulking via various transcranial approaches was considered to be effective at controlling tumor growth, but with high rates of severe surgery-related complications. In the present case, endoscopic transsphenoidal surgery was initiated to debulk the exophytic chiasmatic/hypothalamic glioma with good preservation of hypothalamic and endocrine functions. The authors suggest transsphenoidal surgery with tumor debulking could be an effective and safe treatment for patients with chiasmatic/hypothalamic gliomas. Address correspondence and reprint requests to Zhiping Li, MD, Department of Neurosurgery, Zhucheng People's Hospital, No. 59 Southern Ring Road, Zhucheng City, Shandong Province 86-262200, China; E-mail: zhipingli001@126.com Received 21 January, 2018 Accepted 13 February, 2018 JW and JJ equally contributed to this study. The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Subunit Reconstruction of Mid-Facial Defects With Free Style Facial Perforator Flaps

Introduction: Reconstruction of facial defects is not only important for cosmesis but also for the function. Local flaps are considered the best reconstruction method for facial defects. The authors want to show the feasibility of free style facial perforator flap for the reconstruction of moderate sized mid-facial defects. Methods: Free style facial artery and lateral nasal artery perforator flaps were performed in 22 patients (11 males and 11 females) who had removal of facial tumor between March 2015 and December 2016 Results: The median age of patients was 62 years (range: 35–84). The mean follow-up period was 12.6 months (range: 5–24). Pathology results were basal cell carcinoma in 13 patients, squamous cell carcinoma in 6 patients, and other skin tumors in 3 patients. The defect size ranged from 2 × 2 to 5 × 5 cm. No major or minor complication happened but 1 flap had venous congestion that healed without any intervention Conclusion: Free style facial perforator flaps are highly reliable flaps with wide range of motion. In addition, they provide single-stage closure with esthetic subunit reconstruction. With the current knowledge of reconstruction and skills of microsurgery, they can be easily the first choice for the closure of mid-facial defects. Address correspondence and reprint requests to Utku Can Dölen, MD, Division of Plastic Surgery, Washington University in St Louis, St Louis, MO; E-mail: utkuchan@gmail.com Received 24 December, 2017 Accepted 9 February, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Outcome of Conventional Adipose Tissue Grafting for Contour Deformities of Face and Role of Ex Vivo Expanded Adipose Tissue-Derived Stem Cells in Treatment of Such Deformities

Objectives: To evaluate the outcomes of conventional fat grafting for facial contour deformities and to describe clinical outcome of a patient with contour deformity of face treated with ex vivo expanded adipose tissue-derived mesenchymal stem cells (ASCs) enriched fat graft. Place and Duration of Study: The Department of Plastic Surgery and Tissue Engineering and Regenerative Medicine Laboratory, King Edward Medical University/Mayo Hospital, Lahore, from September 2015 to September 2017. Methods: Patients with contour deformities of face requiring soft tissue augmentation were included. Fat was harvested, processed, and injected following a standard protocol. Both subjective and objective assessments were performed and complications were also noted. Results: Twenty-five patients underwent 51 fat-grafting sessions over a period of 24 months. Eighteen (72%) patients underwent multiple fat-grafting sessions. Mean (standard deviation) soft tissue thickness after 72 hours and 6 months of first fat graft session was 18.62 (7.2) and 12.88 (6.21) mm, respectively, which corresponds to 30.77 (13)% reduction of transplanted fat. Physician and patient assessment scores were 3.42 (0.92) and 4 (1.04), respectively. Few minor complications were observed. In the patient undergoing ex vivo expanded ASCs enriched fat graft, there was minimal decrease in soft tissue thickness of treated area (44 mm vs 42 mm) 6 months postoperatively and patient was highly satisfied with the outcome after the single session. Conclusion: Conventional fat grafting is safe for correction of facial contour deformities. However, procedure needs to be repeated multiple times to produce satisfactory results. Beneficial effects of ex vivo expanded ASCs enriched fat grafting have a potential to alter the current treatment paradigm of fat grafting for soft tissue reconstruction. Address correspondence and reprint requests to Dr Mahmood S. Choudhery, PhD, Assistant Professor, Tissue Engineering and Regenerative Medicine Laboratory, Department of Biomedical Sciences, King Edward Medical University, Lahore, Pakistan; E-mail: drmahmood@kemu.edu.pk Received 24 October, 2017 Accepted 18 December, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Metabolic and Psychological Impact of a Pragmatic Exercise Intervention Program in Adolescent and Young Adult Survivors of Pediatric Cancer-Related Cerebral Insult

Journal of Adolescent and Young Adult Oncology, Ahead of Print.

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Effectiveness of an oral health intervention program for children with congenital heart defects

Abstract

Background

Children with congenital heart defects (CHD) are reported to have poorer oral health compared with healthy children. The aim of the present study was to evaluate the effectiveness of an intensive oral health care program among children with CHD followed from infancy to the age of 5 years, by comparing their oral health status at 5 years with a control group of children with CHD who had not received the program.

Methods

In this longitudinal study, children in western Norway with a need for lifelong follow-up due to congenital heart defects were invited to participate (n = 119). Children born in 2008–2011 were offered an oral health intervention program from infancy to the age of 5 years. The outcome measures for evaluating the intervention were dental caries prevalence, dental erosion, plaque index and gingival bleeding index. The data of the intervention group were compared with cross sectional oral health data of 5 year old controls with CHD born 2005–2007 (already published).

Results

Early oral health intervention did not affect the prevalence of caries (25.3% versus 25.4%) or dental erosion (22.2% versus 19.7%) of children with CHD assessed at 5 years. Children in the intervention group were less likely than those in the control group to present with both dental plaque and gingival bleeding at age 5 years. In spite of no difference in caries prevalence between the groups, caries affected children (d_1-5mft) in the intervention group had fewer teeth affected by caries than children in the control group (p = 0.06). The care index was reported to be higher in the intervention group compared with the control group, implying that fewer children in the intervention group suffered from untreated dentine caries. Parents in the intervention group were more likely to brush their children's teeth twice a day than parents of children in the control group.

Conclusion

The oral health promotive program did not influence the prevalence of caries nor dental erosion. However, the findings indicated better oral hygiene, reduced gingival bleeding and less untreated dentine caries in the intervention compared with the control group.

Trial registration

ClinicalTrials.gov NCT03311438. Registration date: October 17th 2017, retrospectively registered.

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Predicting complications of major head and neck oncological surgery: an evaluation of the ACS NSQIP surgical risk calculator

Abstract

Background

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) universal surgical risk calculator is an online tool intended to improve the informed consent process and surgical decision-making. The risk calculator uses a database of information from 585 hospitals to predict a patient's risk of developing specific postoperative outcomes.

Methods

Patient records at a major Canadian tertiary care referral center between July 2015 and March 2017 were reviewed for surgical cases including one of six major head and neck oncologic surgeries: total thyroidectomy, total laryngectomy, hemiglossectomy, partial glossectomy, laryngopharyngectomy, and composite resection. Preoperative information for 107 patients was entered into the risk calculator and compared to observed postoperative outcomes. Statistical analysis of the risk calculator was completed for the entire study population, for stratification by procedure, and by utilization of microvascular reconstruction. Accuracy was assessed using the ratio of predicted to observed outcomes, Receiver Operating Characteristics (ROC), Brier score, and the Wilcoxon signed–ranked test.

Results

The risk calculator accurately predicted the incidences for 11 of 12 outcomes for patients that did not undergo free flap reconstruction (NFF group), but was less accurate for patients that underwent free flap reconstruction (FF group). Length of stay (LOS) analysis showed similar results, with predicted and observed LOS statistically different in the overall population and FF group analyses (p = 0.001 for both), but not for the NFF group analysis (p = 0.764). All outcomes in the NFF group, when analyzed for calibration, met the threshold value (Brier scores < 0.09). Risk predictions for 8 of 12, and 10 of 12 outcomes were adequately calibrated in the FF group and the overall study population, respectively. Analyses by procedure were excellent, with the risk calculator showing adequate calibration for 7 of 8 procedural categories and adequate discrimination for all calculable categories (6 of 6).

Conclusion

The NSQIP-RC demonstrated efficacy for predicting postoperative complications in head and neck oncology surgeries that do not require microvascular reconstruction. The predictive value of the metric can be improved by inclusion of several factors important for risk stratification in head and neck oncology.

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The working road map in a neurosurgical Hybrid Angio-Surgical suite------ development and practice of a neurosurgical Hybrid Angio-Surgical suite

Abstract

Background

The concept of a Hybrid Angio-Surgical Suite (HASS) has emerged as a solution to the complexity of cerebrovascular surgery and the need for immediate intraoperative feedback. When to use it, what cases are suitable for its use, who can use it and how to use it remain debatable.

Objective

Provide the information regarding the application of the HASS for hospital, neurosurgeon and interventionalist.

Methods

We review the literatures of case reports and studies on the use of the hybrid angio-sugical suite along with application of HASS in our own practice.

Results

Indications for using HASS on different types of cerebral vascular disease, including cerebral aneurysm, AVM, DAVF, carotid and vertebral stenosis/occlusion, are addressed. The application of HASS for other non-cerebral vascular diseases, such as trauma, spine and skullbase cases, is reviewed and discussed.

Conclusion

HASS has made many surgical procedures safer and many difficult or previously untreatable conditions much more tractable and cost-effective. Other than used in cerebral vascular disease, HASS has much more applications, such as trauma, spine and other neurosurgical diseases.

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Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies

Publication date: Available online 22 March 2018
Source:Cancer Cell
Author(s): Frederick Arce Vargas, Andrew J.S. Furness, Kevin Litchfield, Kroopa Joshi, Rachel Rosenthal, Ehsan Ghorani, Isabelle Solomon, Marta H. Lesko, Nora Ruef, Claire Roddie, Jake Y. Henry, Lavinia Spain, Assma Ben Aissa, Andrew Georgiou, Yien Ning Sophia Wong, Myles Smith, Dirk Strauss, Andrew Hayes, David Nicol, Tim O'Brien, Linda Mårtensson, Anne Ljungars, Ingrid Teige, Björn Frendéus, Martin Pule, Teresa Marafioti, Martin Gore, James Larkin, Samra Turajlic, Charles Swanton, Karl S. Peggs, Sergio A. Quezada
With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8⁺ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

Graphical abstract

Teaser

Arce Vargas et al. use a mouse model expressing human FcγRs to show that antibodies with isotypes equivalent to ipilimumab increase the CD8⁺ to Treg ratio by depleting intra-tumoral Tregs to promote tumor rejection. In melanoma patients, response to ipilimumab is associated with a high affinity FcγR polymorphism.

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Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies

Publication date: Available online 22 March 2018
Source:Cancer Cell
Author(s): Xiaojie Yu, H.T. Claude Chan, Christian M. Orr, Osman Dadas, Steven G. Booth, Lekh N. Dahal, Christine A. Penfold, Lyn O'Brien, C. Ian Mockridge, Ruth R. French, Patrick Duriez, Leon R. Douglas, Arwen R. Pearson, Mark S. Cragg, Ivo Tews, Martin J. Glennie, Ann L. White
Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes.

Graphical abstract

Teaser

CD40 agonist mAbs are being investigated for cancer treatment, whereas antagonistic mAbs are under investigation for the treatment of autoimmune and inflammatory conditions. Yu et al. show that the activity of a CD40 mAb is determined by an interplay between the location of its epitope within CD40 and its isotype.

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Editorial Board

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Melanoma and Immune Checkpoint Inhibitors

Abstract

Purpose of Review

Prognosis of patients with advanced melanoma is dismal with a median overall survival of about 8 months and 5-year overall survival from a diagnosis of metastatic disease of roughly 10%. However, immune checkpoint inhibitors have brought indispensable benefits to melanoma patients. Here we will review the recent clinical efficacy and adverse events of immune checkpoint inhibitors for melanoma patients.

Recent Findings

The immune checkpoint inhibitors increase confirmed objective response and prolong progression-free and overall survival of the afflicted patients in association with maintaining their quality of life. Although diverse immune-related adverse events occur, most of them are manageable by appropriate immunomodulating agents. Clinical efficacy of immune checkpoint inhibitors continues even after discontinuation of drugs.

Summary

Compared with conventional therapeutic options, the immune checkpoint inhibitors appear to prolong the survival of patients with advanced melanoma. Further clinical trials are warranted to determine whether their combinatory use with other treatment options may augment benefits or not.

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Mucosal Melanoma: a Literature Review

Abstract

Purpose of review

Mucosal melanoma is of great interest due to its aggressive behavior and less favorable prognosis. The literature is mainly case reports and case series. Here, we will collect the knowledge on mucosal melanoma from the last decade and review the literature. The main focus is being site-specific clinical features, treatment, and prognosis.

Recent findings

The use of immunotherapy gain ground as for others subsets of melanoma. Anti-CTLA-4 and anti-PD-1/ PD-L1 blockade in mucosal melanoma have been evaluated in recent studies. Clinical trials are ongoing.

Summary

The etiology of mucosal melanomas remains unknown. Head and neck mucosal melanomas are most common. Wide excision surgery is the treatment of choice. The effect of adjuvant therapy on survival remains questionable due to the limited knowledge. Radiotherapy seems to give better local control. The overall five-year survival rate for mucosal melanomas is 0–45%. Recent data indicates that this may be improved by the immunotherapy in the years to come.

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Optimizing Amikacin Dosage in Pediatrics Based on Population Pharmacokinetic/Pharmacodynamic Modeling

Abstract

Objective

Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens.

Methods

We performed a retrospective chart review in non-critical pediatric patients (aged 1–12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets.

Results

The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (C_peak)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values.

Conclusion

The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.

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Cost-Effectiveness Analysis for Soil Heavy Metal Contamination Treatments

Abstract

Soil heavy metal contamination results in both huge economic loss and severe health problem. Many technologies, such as soil stabilization/solidification, soil excavation, soil washing, chemical extraction and phytoremediation, have been developed to treat soil heavy metal contamination. Among these methods, phytoremediation is usually regarded as a promising, environment-friendly, and cost-effective method. However, little information has been found to support this idea. Hence, in this study, we have conducted a cost-effectiveness analysis of three treatment methods (soil excavation and disposal, soil washing, and phytoextraction) in 16 scenarios of different soil texture, site scale, soil metal, and contamination levels with reviewed literature information. The results have showed that phytoextraction is more cost-effective when dealing with the slightly polluted soils, while soil washing is cost-effective for severely-contaminated scenarios.

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Percutaneous cement discoplasty for the treatment of advanced degenerative disk disease in elderly patients

Abstract

Purpose

The authors describe a percutaneous technique to treat advanced degenerative disk disease in elderly patients.

Method

A step-by-step technical description based on our experience in selected cases.

Result

Postoperative imaging results are presented as well as indications and recommendations.

Conclusion

Percutaneous discoplasty can result as an alternative minimal invasive strategy for the treatment of advanced degenerative disk disease.

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Effect of Splenectomy on Serum Cytokine Profiles in Hepatitis B Virus-Related Cirrhosis Patients with Portal Hypertension

Viral Immunology, Ahead of Print.

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Intracell Heat Shock Protein 70 Expression and Nasopharyngeal Carcinoma Stage

Abstract

Tumor growth and metastasis in nasopharyngeal carcinoma (NPC) patients recent research stated that intracellular Hsp70 is a stress protein as the main factor for the growth, invasion and metastasis of NPC. To analyze intracellular Hsp70 protein expression of NPC patients which correlate with staging of NPC as clinical manifestation. Formalin-fixed paraffin-embedded biopsy specimens from 20 NPCs histopathology and clinically. The expression of intracellular Hsp70 was obtained using monoclonal antibody of Anti Human Hsp70 from Santa Cruz Biotechnology, California, USA. The assessment of the staining was performed with Remmele methode by Histopathologies doctor Consultant. 20 NPC patients met the inclusion and exclusion criteria. The data showed a negative intracellular of Hsp70 expression by 15% for all sample that consist of 1 patient of stage I, II, III, and none for stage IV. Then, followed by 25% of mild positive intracellular Hsp70 expression which consisted of 0 patient of stage I and III, 2 patients of stage II, and 3 patients of stage IV. Followed by 50% of moderate positive intracellular Hsp70 expression which consisted of 0 patient of stage I and II, 1 patient of stage III, and 9 patients of stage IV. Spearman test results test scored p = 0.001 with a correlation coefficient of 0.671. The correlation of intracellular Hsp70 protein expression with stage (I, II, III, and IV) in NPC patients was significant (p < 0.05). There was a correlation between increased intracellular Hsp70 expression and the stage of patients with nasopharyngeal carcinoma.

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Post Parotidectomy Quality of Life in Patients with Benign Parotid Neoplasm: A Prospective Study

Abstract

Parotid tumours are not uncommon. The management is surgical for benign and malignant parotid neoplasm. Due to the location of parotid gland and its intricate relationship with facial nerve, cosmetic and functional outcomes after parotid surgery are extremely important. Objectives of the study were to analyse facial nerve functions with emphasis on the quality of life of patients undergoing surgery for parotid neoplasm. A prospective study was conducted on patients presented with parotid neoplasm and undergone parotid surgery. Patient with malignant neoplasm were excluded. 30 patients with benign parotid neoplasm in final histopathology were included in the study. Post operative assessment of facial nerve was done using postparotidectomy facial nerve grading system. Symptom-specific QOL was assessed with the parotidectomy outcome inventory-8. Aesthetic outcome was evaluated with an ordinal scale. Posterior belly of digastric muscle and tragal pointer were the commonest landmark used for facial nerve identification. Temporary facial nerve dysfunction was present in six (20%) patients with marginal mandibular branch most commonly involved. 96% of the female patients and 91% of the male patients rated the cosmetic result as good or very good. A statistically significant difference is noted between superficial parotidectomy and total Parotidectomy for cosmetic outcome and sensory impairment. We noted that changed appearance due to resection of the parotid gland and scar and sensory impairment in the area affect the quality of life of patients and such affect are more after total conservative parotidectomy.

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Dermatofibrosarcoma Protuberans of the Neck: A Brief Review of the Literature

Abstract

Dermatofibrosarcome protuberance (DFSP) is a rare, slow growing soft tissue sarcoma with fibroblastic origin, which has a great, potential of local invasion and recurrence. Because of its unspecific appearance and slow growth features it is commonly misdiagnosed as other benign lesions that leads to a late accurate diagnosis or an inadequate initial treatment. A young female patient with DFSP on the neck who was initially misdiagnosed as lipoma and then underwent inadequate initial resection is presented in this case.

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Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells from lung cancer patients following long-term cancer peptide vaccination

Abstract

Therapeutic cancer peptide vaccination is an immunotherapy designed to elicit cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic vaccination trials have been performed, nevertheless there are only a few reports that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen-specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral blood mononuclear cells (PBMCs) from two lung cancer patients over the course of long-term vaccine therapy. In both patients, vaccination with two epitope peptides derived from cancer/testis antigens (upregulated lung cancer 10 (URLC10) and cell division associated 1 (CDCA1)) induced specific CTLs expressing various TCRs. All URLC10-specific CTL clones tested showed Ca²⁺ influx, IFN-γ production, and cytotoxicity when co-cultured with URLC10-pulsed tumor cells. Moreover, in CTL clones that were not stained with the URLC10/MHC-multimer, the CD3 ζ chain was not phosphorylated. NGS of the TCR repertoire of bulk PBMCs demonstrated that the frequency of vaccine peptide-specific CTL clones was near the minimum detectable threshold level. These results demonstrate that vaccination induces antigen-specific CTLs expressing various TCRs at different time points in cancer patients, and that some CTL clones are maintained in PBMCs during long-term treatment, including some with TCRs that do not bind peptide/MHC-multimer.

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Toward methylation-based classification of central nervous system tumors

Precise classification of nervous system tumors into coherent clinicopathologic entities is the necessary first step for the appropriate management of patients. While this has been traditionally performed by histopathology only, recent accelerations in our understanding of the molecular features of nervous system tumors have led to the integration of molecular characteristics into diagnostic criteria. The updated WHO 2016 classification of tumors of the central nervous system (CNS)¹ thus includes both histologic and molecular features—primarily mutational status of individual genes and copy number alterations—facilitating the precise diagnosis of CNS tumors. While this has led to increased objectivity and reproducibility, classification progress is still required, especially for rare and for poorly understood entities.

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Acta Neurologica Scandinavica, Ahead of Print.

Acta Neurologica Scandinavica, Ahead of Print.

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Acta Neurologica Scandinavica, Ahead of Print.

Acta Neurologica Scandinavica, Ahead of Print.

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Carotid arteritis causing amaurosis fugax and ischaemic cerebrovascular events in neurosarcoidosis

Publication date: Available online 22 March 2018
Source:Clinical Neurology and Neurosurgery
Author(s): D.P. Kidd, D.J. McCabe, T. Wilhelm, M. Galloway
ObjectiveTo present and review the vascular consequences of arteritis in neurosarcoidosis.Patient and methods: neurosarcoidosis is typically an inflammatory disorder of the meninges surrounding the brain and spinal cord. Although inflammation of small and medium sized vessels is seen pathologically and vasculitis is occasionally described, a large intracerebral arteritis has not previously been reported. A few case reports exist, however, which describe the vascular consequences of large vessel compromise in the disorder. We review the literature and present a new case with novel MRI features which imply carotid arteritis.ResultsThe case presented with a disorder of the carotid artery on one side leading to a series of TIAs. Inflammation of the wall of the carotid artery was seen adjacent to a granulomatous leptomeningitis. The disorder responded to immunosuppressive therapy without recurrence.ConclusionsThe imaging features suggest a granulomatous infiltration of the carotid artery wall leading to arteritis followed by disorganisation of the internal elastic lamina and fibrosis. The data provide further insight into the pathogenesis of neurological impairments in neurosarcoidosis. The MRI features of carotid arteritis in neurosarcoidosis have not previously been demonstrated.

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Fatigue in Parkinson’s disease: Metric properties of the fatigue impact scale for daily use (D-FIS), and its impact on quality of life

Publication date: Available online 22 March 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Marcos Serrano-Dueñas, Rosaura Bravo, Tamara Merchán, Maite Serrano
ObjectiveIn Parkinson's disease patients, fatigue is a disabling non-motor symptom whose prevalence ranges from 28% to 58%. The Fatigue Impact Scale for Daily Use (D-FIS), one of the various scales for quantifying fatigue. The aim of our study was to analyze the metric properties of the D-FIS in PD subjects and assess the impact of fatigue on their quality of life.Patients and MethodsThe cohort in this study was comprised of 211 consecutive patients with a PD diagnosis regularly followed up at the Movement Disorders Unit of the Neurology Department at Carlos Andrade Marín Hospital (HCAM) in Quito, Ecuador, according to the United Kingdom PD Society Brain Bank criteria. Data Quality, Acceptability, Reliability, Stability (test-retest), Validity and Multiple linear regression analysis were determined.ResultsThe final sample consisted of 138 men (65.4%) and 73 women. Forty-six percent of these (98 patients) were in stage II of H&Y. We obtained a Cronbach's α value of 0.912 and an ICC value of 0.79. D-FIS was strongly correlated with depression (Spearman rho [Srho] 0.60), anxiety (Srho 0.59), quality of life (Srho 0.67), and non-motor symptoms (Srho 0.66). The scale's discriminant validity, assessed among the different stages of H&Y by the Kruskal-Wallis test, showed major significance (X² = 23.183, p ≤ 0,000). In the Multiple linear regression study, the resulting model proves that fatigue has a determining effect on quality of life.ConclusionsThe D-FIS has good metric properties and demonstrates that fatigue significantly affects PD patients' quality of life and that its impact is independent from that of anxiety, depression, and sleep disorders.

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Intracell Heat Shock Protein 70 Expression and Nasopharyngeal Carcinoma Stage

Abstract

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Post Parotidectomy Quality of Life in Patients with Benign Parotid Neoplasm: A Prospective Study

Abstract

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Population attributable fractions continue to unmask the power of prevention

Population attributable fractions continue to unmask the power of prevention

Population attributable fractions continue to unmask the power of prevention, Published online: 23 March 2018; doi:10.1038/s41416-018-0062-5

Population attributable fractions continue to unmask the power of prevention

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The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015

The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015

The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015, Published online: 23 March 2018; doi:10.1038/s41416-018-0029-6

The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015

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Partial breast irradiation with CyberKnife after breast conserving surgery: a pilot study in early breast cancer

Abstract

Background

Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer.

Methods

This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result.

Results

Mean pathological tumor size was 10.5 mm (±4.3, range 3–18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched.

Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107–213; range:56–325) with a median PTV isodose prescription of 86.0% (IQR 85.0–88.5; range:82–94). The median PTV was 88.1 cm3 (IQR 63.8–108.6; range:32.3–238.8). The median breast V100 and V50 was 0.6 (IQR 0.1–1.5; range:0–13) and 18.6 (IQR 13.1–21.7; range:7.5–37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7–27.6; range 22.3–29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer.

Conclusions

These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results.

Trial registration

The present study is registered at Clinicaltrial.gov (NCT02896322). Retrospectively egistered August 4, 2016.

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Cytological diagnosis of mazabraud's syndrome

Faheema Hasan, Vishal Dhingra, Anshul Singh, Vatsala Misra

Journal of Cytology 2018 35(2):128-129

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Unusual metastasis of medullary thyroid carcinoma to the breast: A cytological and histopathological correlation

Parul Tanwar, Jatin S Gandhi, Anila Sharma, Manoj Gupta, Partha S Choudhary

Journal of Cytology 2018 35(2):117-120

Breast metastases are a relatively rare condition and account for approximately 0.5–2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging. We present the case of a 45-year-old female presenting with a lump breast, which was later found out to be metastasis from medullary carcinoma thyroid.

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Role of endoscopic ultrasound-guided fine-needle aspiration in adrenal lesions: analysis of 32 patients

Rakesh K Gupta, Kaushik Majumdar, Ravindra K Saran, Siddharth Srivastava, Puja Sakhuja, Vineeta V Batra

Journal of Cytology 2018 35(2):83-89

Objective: Endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) is a precise and safe technique that provides both radiological and pathological diagnosis with a better diagnostic yield and minimal adverse events. EUS-FNAC led to the remarkable increase in the detection rate of incidentaloma found during radiologic staging or follow-up in various malignancy or unrelated conditions. Aims: We did this preliminary study with an aim to evaluate the role of EUS-FNA in diagnosing and classifying adrenal lesions, clinical impact, and compare the outcome with the previously published literature. Materials and Methods: We included 32 consecutive cases (both retrospective and prospective) of EUS-guided adrenal aspirate performed over a period of 3.3 years. The indications for the aspirate in decreasing order were metastasis (most common carcinoma gall bladder) > primary adrenal mass > disseminated tuberculosis > pyrexia of unknown origin. On EUS, 28 cases revealed space occupying lesion or mass (two cases bilateral) and four cases revealed diffuse enlargement (two cases bilateral) with a mean size of 21 mm. Results: The cytology reports were benign adrenal aspirate (43.8%), metastatic adenocarcinoma (15.6%), histoplasmosis (9.4%), tuberculosis (9.4%), round cell tumor (6.2%), adrenocortical carcinoma (3.1%), and descriptive (3.1%). Three cases (9.4%) yielded inadequate sample. The TNM staging was altered in 22.23% of the cases by result of adrenal aspirate. Conclusions: EUS-FNA of the adrenal gland is a safe, quick, and sensitive and real-time diagnostic technique, which requires an integrated approach of clinician, endoscopist, and cytopathologist for high precision in diagnosis. Although the role of EUS-FNA for right adrenal is not much described, we found adequate sample yield in all the four patients that underwent the procedure.

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Pilot study of an open-source image analysis software for automated screening of conventional cervical smears

Parikshit Sanyal, Prosenjit Ganguli, Sanghita Barui, Prabal Deb

Journal of Cytology 2018 35(2):71-74

Introduction: The Pap stained cervical smear is a screening tool for cervical cancer. Commercial systems are used for automated screening of liquid based cervical smears. However, there is no image analysis software used for conventional cervical smears. The aim of this study was to develop and test the diagnostic accuracy of a software for analysis of conventional smears. Materials and Methods: The software was developed using Python programming language and open source libraries. It was standardized with images from Bethesda Interobserver Reproducibility Project. One hundred and thirty images from smears which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and 45 images where some abnormality has been reported, were collected from the archives of the hospital. The software was then tested on the images. Results: The software was able to segregate images based on overall nuclear: cytoplasmic ratio, coefficient of variation (CV) in nuclear size, nuclear membrane irregularity, and clustering. 68.88% of abnormal images were flagged by the software, as well as 19.23% of NILM images. The major difficulties faced were segmentation of overlapping cell clusters and separation of neutrophils. Conclusion: The software shows potential as a screening tool for conventional cervical smears; however, further refinement in technique is required.

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Gata3 immunohistochemical staining is a useful marker for metastatic breast carcinoma in fine needle aspiration specimens

Paul W Shield, Stephen J Crouch, David J Papadimos, Michael D Walsh

Journal of Cytology 2018 35(2):90-93

Aims: The utility of GATA3 immunohistochemistry (IHC) as an aid to the cytological diagnosis of metastatic breast carcinoma in fine needle aspiration (FNA) specimens was investigated. Materials and Methods: Cell block sections from 111 FNA cases of metastatic malignancy were stained for GATA3, including metastases from 43 breast and 44 nonmammary adenocarcinomas, 19 melanomas, 4 urothelial carcinomas, and 1 thyroid medullary carcinoma. Sites sampled included lymph nodes (87), bone (8), liver (5), lung (6), superficial masses (4), and pelvic mass (1). Results: Ninety-one percent (39/43) of metastatic breast carcinoma cases were positive for GATA3. All estrogen receptor (ER)-positive were also GATA3 positive cases. The majority (9/14; 64%) of ER-negative and 37% (3/8) of triple-negative cases were positive for GATA3. All nonmammary adenocarcinoma cases were negative with the exception of one case of metastatic pancreatic adenocarcinoma. Metastatic melanoma cases were all negative but 75% (3/4) urothelial carcinomas expressed GATA3. Conclusions: GATA3 IHC staining is a useful addition to IHC panels for FNA samples in specific settings such as distinguishing metastatic breast from lung carcinoma or melanoma.

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Primary splenic angiosarcoma with liver metastasis: A rare neoplasm diagnosed on fine-needle aspiration cytology and cell block immunocytochemistry

Saniya Sharma, Priya Singh, Pankaj Gupta, Anupam Lal, Radhika Srinivasan

Journal of Cytology 2018 35(2):114-116

Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal origin. The tumor is highly aggressive and has a high metastatic potential. It is usually diagnosed on histopathological examination of splenectomy specimen. Only few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA) cytology alone have been reported in the literature. The cytologic features of angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when vasoformative features are present. A 55-year-old female presented with abdominal pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous splenic lesion with liver metastases. FNA from the splenic and liver lesions showed moderately pleomorphic tumor cells closely associated with anastomosing vascular channels. Cell block immunocytochemistry (ICC) showed tumor cells positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block ICC can render a definite diagnosis of primary splenic angiosarcoma with liver metastasis.

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Comparison of conventional smear and liquid-based cytology preparation in diagnosis of lung cancer by bronchial wash and transbronchial needle aspiration

Aasma Nalwa, Ritika Walia, Varsha Singh, Karan Madan, Sandeep Mathur, Venkateshwaran Iyer, Deepali Jain

Journal of Cytology 2018 35(2):94-98

Introduction: Liquid-based cytology (LBC), initially developed for screening gynecologic specimens, is now being used in nongynecologic aspiration and exfoliative specimens. In this study, the diagnostic yield and utility of thin-prep (TP) was compared with conventional preparations to ascertain its utility in improving the diagnosis of respiratory lesions. Materials and Methods: Bronchial washings (BW) and transbronchial needle aspirates (TBNA) (bronchoscopy/endobronchial ultrasound-guided) from 70 consecutive patients of mediastinal masses and endo/peribronchial growths were included. The diagnostic yields of both conventional smears and thin-prep were compared. Immunocytochemistry (ICC) was performed on direct/cytospin smears of TBNA/BW and TP slides when the tumor could not be subtyped by morphology. Histopathologic correlation was done. Results: Although well-preserved morphological features and cleaner background in TP allowed accurate diagnosis of malignancies, diagnostic yield was comparable to conventional preparations. Immunocytochemistry was successfully employed on TP smears which helped in accurate subtyping of the tumors. Few shortcomings of TP smears were uneven distribution of cells, thick cell clusters, and inadequate cellularity. Conclusion: Liquid-based TP preparation is an effective diagnostic tool for respiratory tract cytology, however, results are comparable to conventional smears.

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Retinoblastoma in an adult

Vasudha Garg, Ashumi Gupta, Sonam K Pruthi, Pratima Khare

Journal of Cytology 2018 35(2):120-124

Retinoblastoma is a rare malignant tumor of the retina usually seen in children before 5 years of age. The tumor is extremely rare in adults. We report here an unusual case of retinoblastoma in a 55-year-old adult female who presented to us with an orbital mass at a late stage of the disease. Detailed laboratory investigations and imaging studies could not make a precise diagnosis. The treating ophthalmologist suspected primary intraocular tumor, metastatic carcinoma, malignant melanoma, or lymphoma and referred the patient for fine needle aspiration cytology (FNAC). Cytopathological examination of Giemsa-stained FNAC smear was consistent with that of retinoblastoma and established the diagnosis.

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Analysis of morphological features of benign and malignant breast cell extracted from fnac microscopic image using the pearsonian system of curves

Nijara Rajbongshi, Kangkana Bora, Dilip C Nath, Anup K Das, Lipi B Mahanta

Journal of Cytology 2018 35(2):99-104

Context: Cytological changes in terms of shape and size of nuclei are some of the common morphometric features to study breast cancer, which can be observed by careful screening of fine needle aspiration cytology (FNAC) images. Aims: This study attempts to categorize a collection of FNAC microscopic images into benign and malignant classes based on family of probability distribution using some morphometric features of cell nuclei. Materials and Methods: For this study, features namely area, perimeter, eccentricity, compactness, and circularity of cell nuclei were extracted from FNAC images of both benign and malignant samples using an image processing technique. All experiments were performed on a generated FNAC image database containing 564 malignant (cancerous) and 693 benign (noncancerous) cell level images. The five-set extracted features were reduced to three-set (area, perimeter, and circularity) based on the mean statistic. Finally, the data were fitted to the generalized Pearsonian system of frequency curve, so that the resulting distribution can be used as a statistical model. Pearsonian system is a family of distributions where kappa (Ò) is the selection criteria computed as functions of the first four central moments. Results and Conclusions: For the benign group, kappa (Ò) corresponding to area, perimeter, and circularity was −0.00004, 0.0000, and 0.04155 and for malignant group it was 1016942, 0.01464, and −0.3213, respectively. Thus, the family of distribution related to these features for the benign and malignant group were different, and therefore, characterization of their probability curve will also be different.

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Papillary carcinoma thyroid presenting as huge scalp metastases

Adarsh Barwad, Prashant P Ramteke, Shivanand Gamanagatti

Journal of Cytology 2018 35(2):126-127

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Comparing the efficacy of leishman–giemsa cocktail stain, giemsa stain, and papanicolaou stain in potentially malignant oral lesions: A study on 540 cytological samples

Supreet K Sidhu, Karthikeyan Ramalingam, Sandeep Goyal, Monika Poonia, Gaurav S Rajawat, Nitish Sharma

Journal of Cytology 2018 35(2):105-109

Background: This study was planned to compare and evaluate the staining efficacy of Leishman–Giemsa cocktail (LG), Papanicolaou, and Giemsa stain (G) in potentially malignant disorders and malignant lesions. Aims: To evaluate the quality of nuclear and cytoplasmic staining of LG with G, and rapid Papanicolaou stain (Pap) and to compare the total staining efficiency of LG against G and P. Materials and Methods: One hundred and eighty participants were studied under three groups – 60 as healthy controls, 60 with potentially malignant disorders, and 60 with malignant lesions; smears were taken thrice from the buccal mucosa. One smear was fixed with Bio-Fix spray and other two smears were allowed to air dry for 2–3 minutes. Then, the ethyl alcohol-fixed smear was stained with Pap and the two other air-dried smears were stained with G and LG stains. Analysis was done using Friedman test and Wilcoxon Signed Rank Test with SPSS Version 15.0. Results: In the normal group, staining of LG was highly significant (P < 0.001). Among potentially malignant lesions, LG was observed to be highly significant (P < 0.001) when compared with G and was not significant when compared with Pap (P = 0.186). In the malignant group, LG was highly significant (P < 0.001). LG was superior with the highest average staining score of (2.018) than Pap and G. Conclusion: LG cocktail is a better stain with excellent cytoplasmic and nuclear staining intensity compared to Pap and G stains.

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Cytological findings of a rare case of transitional cell carcinoma bladder presenting with supraclavicular lymphnode metastasis

Sana Ahuja, Nadeem Tanveer, Thaihamdao Haflongbar, Vinod K Arora

Journal of Cytology 2018 35(2):129-130

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Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules

11-2017-0447-endo_10-1055-a-0588-4885-1.

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0588-4885

Background Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. Methods A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. Results A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. Conclusions Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).
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Article in Thieme eJournals:
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False positive plasma genotyping due to clonal hematopoiesis

Purpose: Plasma cell-free DNA (cfDNA) genotyping is increasingly used in cancer care, but assay accuracy is debated. Because most cfDNA is derived from peripheral blood cells (PBC), we hypothesized that nonmalignant mutations harbored by hematopoietic cells (clonal hematopoiesis, CH) could be a cause of false positive plasma genotyping. Experimental Design: We identified patients with advanced NSCLC with KRAS, JAK2, or TP53 mutations identified in cfDNA. With consent, PBC DNA was tested using droplet digital PCR (ddPCR) or next-generation sequencing (NGS) to test for CH-derived mutations. Results: We first studied plasma ddPCR results from 58 EGFR-mutant NSCLC patients. Two had KRAS G12X detected in cfDNA and both were present in PBC, including one where the KRAS mutation was detected serially for 20 months. We then studied 143 plasma NGS results from 122 NSCLC patients, and identified 5 JAK2 V617F mutations derived from PBC. Additionally, 108 TP53 mutations were detected in cfDNA; for 33 of the TP53 mutations, PBC and tumor NGS were available for comparison, and 5 were present in PBC but absent in tumor, consistent with CH. Conclusions: We find that most JAK2 mutations, some TP53 mutations, and rare KRAS mutations detected in cfDNA are derived from CH not tumor. Clinicians ordering plasma genotyping must be prepared for the possibility that mutations detected in plasma, particularly in genes mutated in CH, may not represent true tumor genotype. Efforts to use plasma genotyping for cancer detection may need paired PBC genotyping so that CH-derived mutations are not misdiagnosed as occult malignancy.

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Nontuberculous mycobacterial empyema in an immunocompetent child

Ira Shah, Forum Shah

Indian Journal of Pathology and Microbiology 2018 61(1):141-142

Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium Tuberculosis complex and Mycobacterium leprae. There are very few reports of NTM in immunocompetent children causing empyema. In this article, we report a 9-year-old immunocompetent girl who presented with Mycobacterium avium-intracellulare empyema.

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A practical diagnostic approach to hepatic masses

Monika Vyas, Dhanpat Jain

Indian Journal of Pathology and Microbiology 2018 61(1):2-17

The differential diagnosis of hepatic mass lesions is broad and arriving at the right diagnosis can be challenging, especially on needle biopsies. The differential diagnosis of liver tumors in children is different from adults and is beyond the scope of this review. In adults, the approach varies depending on the age, gender, and presence of background liver disease. The lesions can be divided broadly into primary and metastatic (secondary), and the primary lesions can be further divided into those of hepatocellular origin and nonhepatocellular origin. The first category consists of benign and malignant lesions arising from hepatocytes, while the second category includes biliary, mesenchymal, hematopoietic, and vascular tumors. Discussion of nonepithelial neoplasms is beyond the scope of this review. The hepatocytic lesions comprise dysplastic nodules, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma, and the differential diagnosis can be challenging requiring clinicopathological correlation and application of immunohistochemical (IHC) markers. Liver is a common site for metastasis, sometimes presenting with an unknown primary site, and proper workup is the key to arriving at the correct diagnosis. The correct diagnosis in this setting requires a systematic approach with attention to histologic features, imaging findings, clinical presentation, and judicious use of IHC markers. The list of antibodies that can be used for this purpose keeps on growing continually. It is important for pathologists to be up to date with the sensitivity and specificity of these markers and their diagnostic role and clinical implications. The purpose of this review is to outline the differential diagnosis of hepatic masses in adults and discuss an algorithmic approach to make a right diagnosis.

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Suprasellar schwannoma: A rare occurence

IndianJPatholMicrobiol_2018_61_1_156_228

Urmi Mukherjee, Nayana Patil, Anuj Khurana

Indian Journal of Pathology and Microbiology 2018 61(1):156-157

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Evaluation of the osteopontin in oral peripheral and central giant cell granuloma

Nihan Aksakalli

Indian Journal of Pathology and Microbiology 2018 61(1):18-21

Aim: Peripheral giant cell granuloma (PGCG) and central giant cell granuloma (CGCG) of the jaws are benign proliferations of spindle-shaped mesenchymal cells and multinucleated giant cells. Despite the histopathologic similarities, they have markedly different clinical behavior. PGCG shows low recurrence rate whereas CGCG shows a variable clinical behavior ranging from nonaggressive lesions to aggressive lesions characterizing by pain, rapid growth, and high recurrence rate. Therefore, the aim of the study was to compare CGCG with PGCG by immunohistochemistry using Ki-67, osteopontin (OPN), and integrin αvantibodies. Subjects and Methods: Twenty PGCG and 20 CGCG were selected for immunohistochemical evaluation of OPN, integrin αv, and Ki-67 in multinucleated giant cells and mononucleated cells of PGCG and CGCG. Results: PGCG showed higher Ki-67 immunoreactivity in mononucleated cells compared to CGCG (P < 0.05). There was no reactivity with Ki-67 in multinucleated giant cells of both groups. Mononucleated cells in CGCGs demonstrated increased OPN and integrin αvexpressions in comparison with PGCGs (P < 0.05). Conclusions: The clinic behavior of CGCG being more aggressive than PGCG might be explained by the high expression of OPN and integrin αv. Further studies are necessary to evaluate the other OPN receptors and their role on the biologic behavior of these lesions.

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A rare case of primary female urethral adenocarcinoma: Columnar type with colonic adenocarcinoma features

Prithal Gangadhar, Muktha R Pai, I Sandhya

Indian Journal of Pathology and Microbiology 2018 61(1):127-130

Female urethral carcinoma is extremely rare and accounts for 0.02% of all women's cancers and <1% of cancers in the female genitourinary tract. Adenocarcinoma accounts for only 10% of urethral carcinomas in females. Due to their location, presentation is usually late and tumors are often missed on physical examination. As in this case, nonspecific symptoms in the early stages may delay the diagnosis in most patients. Herein, we present an extremely rare case of the columnar type of primary female urethral adenocarcinoma exhibiting colonic adenocarcinoma features which to the authors' best knowledge has not been reported to date. The present study emphasizes the importance of a careful clinical examination and also highlights the role of imaging studies, and biopsy in making an accurate preoperative diagnosis of this rare disease. The disease may have devastating sequelae due to local and metastatic involvement if not recognized and treated earlier.

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Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum-free light chain assay

IndianJPatholMicrobiol_2018_61_1_149_228

Nabhajit Mallik, Ram Vasudevan Nampoothiri, Sreejesh Sreedharanunni, Man Updesh Singh Sachdeva, Pankaj Malhotra, Neelam Varma

Indian Journal of Pathology and Microbiology 2018 61(1):149-150

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Myeloid cell leukemia-1 protein expression and myeloid cell leukemia-1 gene amplification in non small cell lung cancer

Tony El Jabbour, Siddhartha Dilip Dalvi, Sungeun Kim, Christine Sheehan, Jeffrey S Ross

Indian Journal of Pathology and Microbiology 2018 61(1):27-30

Background: Myeloid cell leukemia-1 (Mcl-1) is a member of the B-cell lymphoma 2 family known to play a significant role in the regulation of apoptosis. Mcl-1 expression has been studied in nonsmall cell lung cancer (NSCLC) cell lines but has not been previously evaluated as a prognostic factor in clinical samples. Materials and Methods: Formalin-fixed, paraffin-embedded sections from 119 NSCLC, including 33 squamous cell carcinomas (SCC), 55 adenocarcinomas (AC), and 31 either pure adenocarcinoma in situ (AIS) or AC with lepidic features were immunostained by an automated method with rabbit polyclonal Mcl-1. Cytoplasmic Mcl-1 (cMcl-1) immunoreactivity was scored based on intensity and percentage of positive tumor cells in both tumor and adjacent benign epithelium in each case. MCL1 amplification was determined by hybrid capture-based comprehensive genomic profiling (CGP) on a separate cohort of 9393 NSCLC samples. Results: Intense diffuse cMcl-1 overexpression was noted in 35/119 (29%) tumors overall and correlated with tumor type (52% AIS vs. 31% AC vs. 6% SCC, P < 0.0001), tumor grade (48% grade 1 vs. 14% grade 2 vs. 31% grade 3, P = 0.007), small tumor size (36% ≤3.0 cm vs. 16% >3.0 cm, P = 0.016), and lengthened survival within the AIS subgroup (100% alive vs. 42% expired, P = 0.018) while showing a trend toward correlation with nonrecurrent disease overall (32% nonrecurrent vs. 11% recurrent, P = 0.072) and within the AC subgroup (33% nonrecurrent vs. 0% recurrent, P = 0.092). MCL1 amplification was identified in 569 (6%) of 9393 NSCLC by CGP. Conclusions: cMcl-1 overexpression appears to occur independently from MCL1 gene amplification in NSCLC and correlates with AIS histologic type, lower tumor grade, smaller tumor size, nonrecurrent disease, and increased survival.

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Undiagnosed tubal high-grade serous carcinoma metastatic to synchronous benign ovarian Brenner tumor

IndianJPatholMicrobiol_2018_61_1_162_228

Abhijit Chougule, Rashi Garg, Pranab Dey

Indian Journal of Pathology and Microbiology 2018 61(1):162-164

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Expression of breast cancer type 1 and its relation with expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2/neu in breast carcinoma on trucut biopsy specimens

Deepti Verma, Kiran Agarwal, Sanjeev Kumar Tudu

Indian Journal of Pathology and Microbiology 2018 61(1):31-38

Objective: (1) The objective is to study the immunohistochemical expression of Breast cancer type 1 (BRCA1) in breast carcinoma on trucut biopsy specimens and (2) To relate its expression with that of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER-2)/neu and the clinicopathological parameters. Settings and Design: A cross-sectional hospital-based study was performed in Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, with collaboration of the Departments of Pathology and Surgery from the period of November 2008 to March 2010. Materials and Methods: The study group included 54 cytologically proven cases of breast carcinoma. The immunohistochemical expression of BRCA1 was studied and related with expression of ER, PR, and HER-2/neu on their trucut biopsies. Results: The altered expression of BRCA1 (i.e., reduced or absent expression) was seen in 44.4% cases of breast carcinoma while 55.6% had positive expression. About 83% of breast carcinomas with altered BRCA1 expression were larger than 3 cm in size. The breast carcinomas showing altered expression were found to be mostly high grade (63.6%). This was statistically significant. The ER and PR negativity were seen in 62.5% and 79.2% breast carcinomas with altered BRCA1 expression, respectively. The score 3 positivity of HER-2/neu was more common among carcinomas with altered BRCA1 expression (21% vs. 16.7%). The triple negativity was found in 41.7% breast carcinomas having altered BRCA1 expression. This was statistically significant. Conclusion: The combination of immunohistochemical expression of BRCA1, ER, PR, and HER-2/neu and clinicopathological details may be helpful in predicting the individuals more likely to carry BRCA1 mutations and thus selecting the candidate and family members for genetic screening for BRCA1 mutations.

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Anastomosing hemangioma with extensive fatty stroma in the retroperitoneum

Ananthvikas Jayaram, Marie Therese Manipadam, Paul Mazhuvanchary Jacob

Indian Journal of Pathology and Microbiology 2018 61(1):120-122

Anastomosing hemangiomas are a recently recognized benign vascular neoplasm, first described by Montgomery and Epstein in 2009. A few cases have been described in the genitourinary tract, especially in the renal hilum. These are fairly well-demarcated lesions with lobules of sinusoidal-like capillaries lined by hobnail endothelial cells containing eosinophilic hyaline globules in the cytoplasm. Extramedullary hematopoiesis has been described in a few cases, along with large feeding vessels. A predominant adipocytic component has been described in only one case.[9] We describe a case of a retroperitoneal anastomosing hemangioma occurring in an extrarenal site in a 53-year-old female, followed by a review of the current literature.

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Immunohistochemical evaluation of lymphovascular invasion in carcinoma breast with CD34 and D2-40 and its correlation with other prognostic markers

Sonal Agarwal, Amarjit Singh, Permeet Kaur Bagga

Indian Journal of Pathology and Microbiology 2018 61(1):39-44

Background: Carcinoma breast is ever-evolving and becoming increasingly prevalent in India. Numerous prognostic factors based on morphology and immunohistochemistry (IHC) have been established which need to be interconnected to give patients best possible treatment. Aims: This study aims to confirm and analyze lymphovascular invasion (LVI) detected by hematoxylin and eosin (H and E) using IHC with CD34 and D2-40 and its correlation with other biologic and morphologic prognostic markers. Settings and Design: This was a prospective study. Materials and Methods: Fifty mastectomy specimens diagnosed as infiltrating ductal carcinoma breast on histopathology selected for the study. Evaluation of formalin-fixed paraffin-embedded sections was done using H and E and IHC for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 HER2/neu receptors, CD34, and D2-40 endothelial markers. Correlation of LVI done with prognostic markers of Carcinoma Breast, namely, age of the patient, tumor size, Nottingham grade, lymph node ratio (LNR), Nottingham prognostic index (NPI), ER/PR status, and HER2/neu status. CD34 and D2-40 utilized to distinguish blood vessel, lymph vessel, and retraction artifacts and to calculate lymphatic microvessel density (LMVD) and blood microvessel density (BMVD). Statistical Analysis Used: SPSS Software Package. Results: LVI was associated with younger age (P = 0.001), greater tumor size (P = 0.007), higher Nottingham grade (P = 0.001), higher LNR (P = 0.001), higher NPI (P = 0.001), Negative ER Status (P = 0.001), Negative PR Status (P = 0.002), Positive HER2/neu status (P = 0.021), Higher Intratumoral BMVD (P = 0.016), Peritumoral BMVD (P = 0.001), and Intratumoral LMVD (P = 0.009). Blood vessels more commonly invaded than lymph vessels. Retraction artifacts can be mistaken for LVI without IHC. Conclusions: D2-40 is a promising marker for lymphatic endothelium. LVI is a poor prognostic marker hence should be evaluated imperatively in all cases of carcinoma breast.

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Αρχειοθήκη ιστολογίου

Πέμπτη 22 Μαρτίου 2018

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