A nomogram to determine required seed air kerma strength in planar 131 Cesium permanent seed implant brachytherapy

Purpose: Intraoperatively implanted Cesium-131 ( 131 Cs) permanent seed brachytherapy is used to deliver highly localized re-irradiation in recurrent head and neck cancers. A single planar implant of uniform air kerma strength (AKS) seeds and 10 mm seed-to-seed spacing is used to deliver the prescribed dose to a point 5 mm or 10 mm perpendicular to the center of the implant plane. Nomogram tables to quickly determine the required AKS for rectangular and irregularly shaped implants were created and dosimetrically verified. By eliminating the need for a full treatment planning system plan, nomogram tables allow for fast dose calculation for intraoperative re-planning and for a second check method. Material and methods: TG-43U1 recommended parameters were used to create a point-source model in MATLAB. The dose delivered to the prescription point from a single 1 U seed at each possible location in the implant plane was calculated. Implant tables were verified using an independent seed model in MIM Symphony LDR™. Implant tables were used to retrospectively determine seed AKS for previous cases: three rectangular and three irregular. Results: For rectangular implants, the percent difference between required seed AKS calculated using MATLAB and MIM was at most 0.6%. For irregular implants, the percent difference between MATLAB and MIM calculations for individual seed locations was within 1.5% with outliers of less than 3.1% at two distal locations (10.6 cm and 8.8 cm), which have minimal dose contribution to the prescription point. The retrospectively determined AKS for patient implants using nomogram tables agreed with previous calculations within 5% for all six cases. Conclusions: Nomogram tables were created to determine required AKS per seed for planar uniform AKS 131 Cs implants. Comparison with the treatment planning system confirms dosimetric accuracy that is acceptable for use as a second check or for dose calculation in cases of intraoperative re-planning

Endoscopic repair of high-flow cranial base defects using a bilayer button.

OBJECTIVES/HYPOTHESIS: Repair of the skull base still begins with a direct repair of the dural defect. We present a new button closure for primary repair of the dura for high flow defects. STUDY DESIGN: Retrospective review. METHODS: We reviewed our 20 cases of primary button grafts and compared the results to the previous 20 high-flow open-cistern cerebrospinal fluid (CSF) cases. Subjects were excluded if they had no violation of the arachnoid space or potential for low-flow CSF leak. The button is constructed so that the inlay portion is at least 25% larger than the dural defect, and the onlay portion is just large enough to cover the dural defect. The two grafts are sutured together using two 4-0 Neurolon sutures and placed with the inlay portion intradurally and the onlay portion extradurally. RESULTS: The button graft repair of open-cisternal defects had a drop in CSF leak complications to 10% (2/20), and these two leaks were repaired with the button technique as the salvage surgery. This is a significant improvement over the 45% leak rate in the prebutton graft group (P \u3c .03). In our button graft group we used nasoseptal flaps on 16/20 repairs, and 1/2 repairs that leaked in the button group did not have a nasoseptal flap. Lumbar drains were used in approximately 38% in both groups (P = .83). CONCLUSIONS: The button graft can be used in conjunction with the nasal septal flap or as a stand-alone repair with good results reducing the postoperative leak rate to 10% for high-flow CSF repairs

Novel Irradiated Axial Rotational Flap Model in the Rodent

Abstract Objectives: To design an easily reproducible rodent rotational skin flap and to evaluate the effects of radiation on flap viability. Methods: Ten rats received 40 Gy irradiation to the abdominal wall. Following a recovery period of one month, a 3 X 8 cm fasciocutaneous flap based axially on the inferior epigastric vessel, was raised and rotated 60 degrees into a contralateral deficit. Five non-irradiated rats underwent the identical procedure as a control. Animals were sacrificed seven days postoperatively, areas of flap necrosis were documented, and histological specimens were taken to compare flap viability and vessel density. Results: 60% of the rats in the irradiated group had necrosis of the distal flap ranging from 1 to 6 cm from the distal edge, whereas none of the animals (0%) in the control group exhibited necrosis (p\u3c0.001). Histology revealed collagen and vascular changes in the irradiated skin. Vascular density analysis revealed a significant difference between radiated and non-radiated flaps; p = 0.004, 0.029 and 0.014 in the distal, middle and proximal segments of the flap respectively. Conclusion: This novel rat axial rotational flap model demonstrates increases flap necrosis and a decrease in vascular density due to the effects of radiation. Using a linear electron accelerator a dose of 40 gy can be delivered to the skin without resulting in devastating gastrointestinal side effects

A systematic review of treating recurrent head and neck cancer: a reintroduction of brachytherapy with or without surgery.

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions: Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts

Taking Free Flap Surgery Abroad: A Collaborative Approach to a Complex Surgical Problem.

Accessibility to health care, especially complex surgical care, represents one of the major health care disparities in developing countries. While surgical teams may be willing to travel to these areas to help address these needs, there are many logistical and ethical dilemmas inherent in this pursuit. We reviewed our approach to the establishment of the team-based surgical outreach program, wherein we perform head and neck free tissue transfer surgery in Haiti. We describe the challenges encountered in the delivery of surgical care as well as ethical dilemmas relevant to surgical outreach trips, highlighting an approach reliant on strong local cooperation. Despite the obstacles in place, our experience shows that free flap surgery can be successfully and ethically performed in these areas of great need

Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma

Transforming growth factor-beta (TGFβ) signaling in cancer is context dependent and acts either as a tumor suppressor or a tumor promoter. Loss of function mutation in TGFβ type II receptor (TβRII) is a frequent event in oral cavity squamous cell carcinoma (SCC). Recently, heterogeneity of TGFβ response has been described at the leading edge of SCC and this heterogeneity has been shown to influence stem cell renewal and drug resistance. Because exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways we investigated whether exosomes contain components of the TGFβ signaling pathway and whether exosome transfer between stromal fibroblasts and tumor cells can influence TGFβ signaling in SCC. We demonstrate that exosomes purified from stromal fibroblasts isolated from patients with oral SCC contains TβRII. We also demonstrate that transfer of fibroblast exosomes increases TGFβ signaling in SCC keratinocytes devoid of TβRII which remain non-responsive to TGFβ ligand in the absence of exosome transfer. Overall our data show that stromal communication with tumor cells can direct TGFβ signaling in SCC

Parallax and Luminosity Measurements of an L Subdwarf

We present the first parallax and luminosity measurements for an L subdwarf, the sdL7 2MASS J05325346+8246465. Observations conducted over three years by the USNO infrared astrometry program yield an astrometric distance of 26.7+/-1.2 pc and a proper motion of 2.6241+/-0.0018"/yr. Combined with broadband spectral and photometric measurements, we determine a luminosity of log(Lbol/Lsun) = -4.24+/-0.06 and Teff = 1730+/-90 K (the latter assuming an age of 5-10 Gyr), comparable to mid-type L field dwarfs. Comparison of the luminosity of 2MASS J05325346+8246465 to theoretical evolutionary models indicates that its mass is just below the sustained hydrogen burning limit, and is therefore a brown dwarf. Its kinematics indicate a ~110 Myr, retrograde Galactic orbit which is both eccentric (3 <~ R <~ 8.5 kpc) and extends well away from the plane (Delta_Z = +/-2 kpc), consistent with membership in the inner halo population. The relatively bright J-band magnitude of 2MASS J05325346+8246465 implies significantly reduced opacity in the 1.2 micron region, consistent with inhibited condensate formation as previously proposed. Its as yet unknown subsolar metallicity remains the primary limitation in constraining its mass; determination of both parameters would provide a powerful test of interior and evolutionary models for low-mass stars and brown dwarfs.Comment: Accepted to ApJ 10 September 2007; 13 pages, 5 figures, 3 tables, formatted in emulateapj styl

Stromal Monocarboxylate Transporter MCT4 is a Poor Prognostic Factor in Squamous Cell Carcinoma

ABSTRACT Introduction: Monocarboxylate transporter 4 (MCT4) is the main exporter of lactate out of cells. It is also a critical component in the glycolytic metabolism of cancer cells. In this study, stromal MCT4 in oral SCC was correlated with risk of recurrence (ROR), extent of primary tumor (pT) and nodal metastasis (pN), perineural invasion (PNI), lymphovascular invasion (LVI), HPV status, extracapsular extension (ECE) and positive margin. Methods: Clinical data were collected for 86 consecutive patients with oral HNSCC. Tissue microarrays (TMA) were constructed from paraffin blocks of resection specimens and stained for MCT4. Immunohistochemistry (IHC) staining was assessed and quantified by digital image analysis with Aperio software. Using a co-localization algorithm we assessed the intensity of staining and the percentage of positive cells in the tumoral stromal cells. Correlations of MCT4 expression with clinicopathological features and survival were studied. Results: Increased IHC staining for MCT4 was strongly associated with an increased risk of recurrence, OR 1.96 (95%CI: 1.17-3.40), presence of PNI, OR 2.25 (95%CI: 1.33-3.95), higher pT, OR 1.68 (95%CI: 0.99-2.89), higher pN, OR 2.07 (95%CI: 1.25-3.57) and presence of LVI, OR 2.21 (95%CI: 1.11-4.67). We didn’t find any significant association between stromal MCT4 expression and HPV status, presence of ECE or positive margin. Conclusions: This study demonstrates that MCT4, a marker of glycolysis in cancer-associated stroma, is highly expressed in oral SCC. The IHC staining pattern of stromal MCT4 suggests that high MCT4 expression appears to be a useful marker for tumor progression and prognosis. We propose MCT4 serves as a new prognostic factor in oral SCC and can act as a potential therapeutic target marker considering pharmacological development of MCT4 inhibitors

Cervical Spine Osteomyelitis after Esophageal Dilation in Patients with a History of Laryngectomy or Pharyngectomy and Pharyngeal Irradiation

Dysphagia is a common sequela of the treatment of head and neck cancer and is frequently managed with esophageal dilation in patients with dysphagia secondary to hypopharyngeal stenosis. Reported complications of esophageal dilation include bleeding, esophageal perforation, and mediastinitis. We examine four cases of cervical spine osteomyelitis presenting as a delayed complication of esophageal dilation for hypopharyngeal stenosis in patients with a history of laryngectomy or pharyngectomy and radiation with or without chemotherapy. The history of head and neck surgery and radiation in these patients further complicates the management of the cervical spine osteomyelitis