Design and development of ferrocene-containing chitosan-cografted-branched polyethylenimine redox conjugates for monitoring free flap failure after reconstructive surgery.

We reported a proof-of-concept study of developing an electrochemical biosensor for prolonged continuous monitoring free flap failure caused by vascular occlusion after reconstructive surgery. Ferrocene (Fc)-containing Chitosan-cografted-Branched Polyethylenimine redox conjugates (CHIT-Fc-co-BPEI-Fc) were used as pH-tuneable matrix to attach the target enzymes (glucose oxidase ≡ GOD and lactate oxidase ≡ LOD, respectively) to build up the corresponding GOD-sensor and LOD-sensor. The sensitivity of GOD-/LOD-sensor was found to be 2.89(±0.06)µA/mM and 2.95(±0.19)µA/mM with a limit of detection (LOD) of 0.047 mM and 0.172 mM, respectively. The sensor performance was further pre-clinically validated via rabbit study, which confirmed that the designed biosensors could electrochemically detect the changes of metabolite levels caused by flap failure within minutes. This sensor protocol is able to be fabricated as embedded biosensor for prolong continuous detection for clinical application/research.

Factors associated with returning to work in head and neck cancer survivors in Singapore: A preliminary exploratory mixed-methods approach study.

BACKGROUND: Little is known about return-to-work (RTW) among Asian head and neck cancer (HNC) survivors. We investigated the prevalence and factors associated with RTW among HNC patients with in Singapore. METHODS: In this cross-sectional mixed-methods study, 80 HNC patients, who had been working prior to diagnosis, completed questionnaires and 15 participated in qualitative interviews to explore perceived barriers and facilitators of RTW. Multivariate logistic regression was used to evaluate factors associated with not-returning-to-work (NRTW) within 6 months of treatment completion. RESULTS: Thirty-five participants reported NRTW 43.8%. Multivariable analysis showed that patients with advanced stage (III-IV) cancer (odds ratios [OR] = 4.51, 95% confidence intervals [CI]: 1.15-13.28, p = 0.006), multi-modality treatment (OR = 4.62, 95% CI: 1.38-15.52, p = 0.013), and pink-collar jobs (OR = 9.30, 95% CI: 1.70-50.83, p = 0.010) had higher odds of NRTW. CONCLUSION: The factors associated with employment after HNC treatment are complex. Identification of key modifiable factors may lead to improved RTW outcomes.

A Head-to-Head Comparison of the Medial Sural Artery Perforator versus Radial Forearm Flap for Tongue Reconstruction.

BACKGROUND: For tongue reconstruction, the radial forearm flap (RFF) is commonly used. In the last decade, the medial sural artery perforator (MSAP) flap has been successfully used with reportedly superior donor-site outcomes. Our study is the first to compare the RFF and MSAP for reconstruction of partial glossectomy defects (<50% of tongue). METHODS: We conducted a retrospective review of 20 patients with partial glossectomy defects reconstructed at a tertiary referral center. Patient demographics, perioperative data, and postoperative complications were analyzed. Objective measures of speech, swallowing, and subjective patient satisfaction with their donor site were recorded. RESULTS: Ten RFF and MSAP were each used, with a mean partial glossectomy defect size of 40.5 and 43.5%, respectively. The MSAP was significantly thicker (7.8 vs. 4.3 mm, p < 0.05) with a longer harvest time (122.5 vs. 75.0 minutes, p < 0.05). There were no cases of free flap failure. Donor-site healing times were comparable, but the MSAP group experienced significantly less donor-site complications (n = 1 vs. n = 7, p < 0.05). Functional outcomes were comparable with 13 patients achieving normal speech and diet after 3 months (MSAP = 6 vs. RFF = 7, p = 1.00). All patients were satisfied with their donor-site outcome with the MSAP group having a marginally higher score. CONCLUSION: Both flaps are good options for partial glossectomy reconstruction. Though more challenging to harvest, the MSAP gives comparable functional results and has become our first reconstructive option given its superior donor-site outcomes.

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma.

Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.

Pairing a prognostic target with potential therapeutic strategy for head and neck cancer.

OBJECTIVES: We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC. MATERIALS AND METHODS: Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3. Validation was performed using immunohistochemistry (IHC) on tissue microarrays (TMAs) of head and neck cancers (n = 333), staining for ATP13A3 and phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA was used to knockdown ATP13A3 expression in patient derived HNSCC cell lines. Protein expression of ATP13A3 and Aurora kinase A was then assessed by immunoblotting. RESULTS: GSEA identified Aurora kinase pathway to be associated with high expression of ATP13A3 (p = 0.026). The Aurora kinase pathway was also associated with a trend towards poor prognosis and tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, the immunohistochemical staining results revealed a significant association between Aurora kinase activity and high ATP13A3 expression (p < 0.001). Knockdown of ATP13A3 in human head and neck cell lines showed decrease in Aurora kinase A levels. CONCLUSION: Tumors with high ATP13A3 are associated with high Aurora kinase activity. This suggests a potential therapeutic role of Aurora kinase inhibitors in a subset of poor prognosis HNSCC patients with overexpression of ATP13A3.

Implementing the Biodesign Process for Medical Device Innovation in Head and Neck Surgery.

Introduction. The Stanford Biodesign process is a needs-driven approach to innovation which begins in the clinical setting and environment and is championed by practicing clinicians and surgeons. Here, our team applied the Stanford Biodesign process through clinical immersion to identify potential unmet clinical needs in the field of head and neck surgery, brainstormed and prototyped solutions to solve the top unmet need, and developed a commercialized medical device. Methods. The team underwent the 3 phases of the Biodesign process: identify, invent, and implement. The team underwent clinical immersion and followed head and neck surgeons from the Department of Head and Neck Surgery for a duration of 1 month. The needs identified were then filtered through a structured process using predefined filters, and a top need was chosen. After multiple rounds of brainstorming and prototyping, a final concept was developed. Results. The team collected 111 unmet needs and designed the in vivo surgical lighting concept that eventually led to the development of the KLARO™ in vivo surgical lighting device with a commercial partner. KLARO™ is a fully flexible 4.6-mm diameter light-emitting diode light strip that is freely bendable to be safely placed into deep cavities during open surgeries. Conclusion. The Biodesign process provides a standardized way to turn these needs into solution to advance the field of head and neck surgery and improve the outcome of patients.

Validity and reliability of the MD Anderson dysphagia inventory in English and Chinese in head and neck cancer patients.

AIMS: Patient-reported outcome measures are important in assessing the impact of dysphagia on quality of life. Our aim was to adapt and examine the cultural validity and reliability of a swallowing-related quality of life measure, the MD Anderson Dysphagia Inventory (MDADI), in English and Chinese, with head and neck cancer patients. METHODS: We adapted the MDADI to Chinese through formal forward-backward translation. Sixty-six head and neck cancer survivors completed the MDADI, Swallowing Quality of Life (SWAL-QOL) questionnaire and Hospital Anxiety and Depression Scale (HADS) in English or Chinese. Swallowing status was scored on the Functional Oral Intake Scale (FOIS). Seventy-four percent (n = 49) of participants completed a repeat administration of the MDADI for test-retest reliability analysis. RESULTS: The MDADI showed high internal consistency reliability (Cronbach's α , 0.82 ≤ α ≤ 0.94), and test-retest reliability in both English (intraclass correlation coefficient, ICC = 0.81) and Chinese (ICC = 0.72). Criterion validity was established through moderate to strong correlations with relevant SWAL-QOL domains. Convergent validity was determined by significant correlations to the HADS and FOIS. Divergent validity was determined by nonsignificant association to the SWAL-QOL Sleep domain. The MDADI also presented as hypothesised to most known-group theoretical constructs. CONCLUSIONS: The MDADI showed good psychometric properties in English and Chinese. This avails a reliable and psychometrically valid MDADI for Chinese speakers.

Impact of Radiotherapy on Neck Dissection Nodal Count in Patients With Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: Our study aimed to review the impact of preoperative radiotherapy (RT) and other factors on the lymph node count of neck dissection (ND) specimens from patients with head and neck cancer (HNC). A retrospective study was conducted on all patients with head and neck cancers who had undergone NDs in Singapore General Hospital between 1992 and 2013. STUDY DESIGN: Retrospective study. METHODS: Patients were categorized into two groups: patients treated with RT with or without chemotherapy before ND and patients who had undergone ND surgery without previous history of RT. The primary endpoint for this study would be the lymph node count from ND. RESULTS: The study cohort consists of 1,024 NDs on 829 patients. There were 597 (58.3%) radical/modified radical NDs involving levels I-V. Within this group, 75 (12.6%) NDs had preoperative RT. Preoperative RT and age were found to significantly reduce nodal yield in both univariate and multivariate analysis in the radical/modified radical ND subgroup. In our multivariate analysis, preoperative RT was shown to decrease the nodal yield by 7.464 (P = .0002, 95% confidence interval [CI]: -11.35 to -3.58). Advanced age independently decreases nodal yield, even after accounting for the effect of RT (P = .0002, 95% CI: -0.27 to -0.08). In addition, preoperative RT has a more pronounced effect in reducing lymph node count in the older age group. CONCLUSIONS: Preoperative RT and advanced age are independent and synergistic factors that reduce nodal count from NDs in patients with head and neck cancers. LEVEL OF EVIDENCE: 4 Laryngoscope, 130: 1947-1953, 2020.

Adherence of head and neck squamous cell carcinoma patients to tumor board recommendations.

BACKGROUND: Multidisciplinary team (MDT) meetings or tumor boards (TBs) are fundamental components of cancer treatment. Although their primary function is improved outcomes, this aspect is often underreported. The main objective of this study was to analyze the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) discussed at TBs, and to compare the effect of adherence and nonadherence to recommended treatment plans on outcomes. METHODS: Retrospective data analysis was conducted of HNSCC patients those who were adherent and nonadherent to TB therapy recommendations during 2008-2009 at a comprehensive cancer center. Fisher's exact test and t test were used for group-wise comparison, and Kaplan-Meier and logistic regression models, for survival analysis and determination of the contributing factors to nonadherence. RESULTS: Comprehensive Treatment plans were recommended by TBs in 293 HNSCC patients with curative intent. Seventy-two patients were excluded based on the selection criteria. Among the remaining 221 patients, 172 (77.9%) were adherent to TB recommendations, while 49 (22.1%) failed to comply. Patient (n = 36; 73.5%), clinician (n = 2; 4.1%), and disease-related (n = 11; 22.4%) factors were significant contributors to nonadherence. Mean (±standard deviation (SD)) survival time was 55.6 ± 2.32 and 29.1 ± 4 months in the adherent and nonadherent groups, (P < .0001, respectively). Multivariate analyses showed that gender, ethnicity, higher T-stage, and multimodal treatment were associated with nonadherence. CONCLUSION: Adherence to TB recommendations improved overall survival, reflecting the importance of interdisciplinary expertise in contemporary cancer treatment. Early identification and intervention is crucial in "at risk" patients to prevent subsequent drop-out from optimal cancer care.

Electronic tumor board presentations as the basis for the development of a head and neck cancer database.

BACKGROUND: Multidisciplinary team meetings or tumor boards (TBs) form a pivotal component of oncology practice. The crux of a TB revolves around making treatment decisions based on succinct head and neck cancer (HNC) patient data presentations, which can be challenging and complex. Apart from meticulous TB presentations, discussions and treatment plan documentation is equally important. The aim of this study was to structure an electronic synoptic TB data presentation to address all these areas. The overarching benefits of systematic TB data collection include facilitating audits and research. METHODS: We utilized a secure web-based tool that was used for common scientific research purposes but customized to store HNC patient data. The data points were tabulated across eight TB pages: (a) TB scheduling, (b) patient biodata, (c) diagnosis details, (d) index presentation, (e) images, (f) management and histopathology, (g) TB presentation, and (h) TB discussion and decisions. Each data point leads to additional fields by branching logic to permit further relevant data entry. This was integrated within the patient electronic medical records allowing for a direct internal trajectory to recall TB data. RESULTS: From October 2015 to October 2018, we recorded over 2000 presentations for 1279 individual patients. This is a quality improvement initiative, and hence, the results are more of a broad analysis of our TB presentation process. The most common cancers were squamous cell (523, 41%), thyroid (207, 16%), and nasopharyngeal (139, 11%) carcinomas. Importantly, this system has formed the basis for a number of clinical and translational research projects and audit outcomes. CONCLUSION: Despite TBs being vital to oncologic practice, little attempt has been made to report TB data management. In this study, we present an efficient system that permits the integration of dual functions: TB data presentation and oncologic data collection for research, recall, and audit purposes.

Comparing the Utility and Surgical Outcomes of Harmonic Focus Ultrasonic Scalpel with Ligasure Small Jaw Bipolar Device in Thyroidectomies: A Prospective Randomized Controlled Trial.

BACKGROUND: Ultrasonic or bipolar radiofrequency energy devices are routinely used for dissection and hemostasis during thyroidectomy. We report a single-center, prospective, randomized controlled trial comparing the utility and outcomes of Harmonic Focus, an ultrasonic coagulating shear device (UCSD), versus Ligasure Small Jaw, an electrothermal bipolar vessel sealer (EBVS) in thyroidectomy (NCT01765686). METHODS: Between December 2012 to January 2016, eligible patients were randomized to undergo hemithyroidectomy using either a UCSD or an EBVS. The primary outcome was duration of surgery. Secondary outcomes included blood loss, postoperative complications, ease of device use, ease of device set-up, vocal cord function, postoperative wound drainage, pain score, and adverse events. RESULTS: Of 110 patients assessed for eligibility, 100 were randomly allocated (UCSD: 49 patients; EBVS: 51 patients) and analyzed by intention-to-treat. There were no differences in specimen delivery time, total duration of surgery, wound drainage, and adverse events between the two groups. The UCSD group had a greater proportion of patients with higher postoperative pain scores in the first 72 h (8.1% vs. 2.0%, p = 0.043). Surgeons reported greater ease of use for the UCSD (49% vs. 27%; p = 0.005), while operating room staff favored the EBVS (60% vs. 33%, p = 0.005). CONCLUSIONS: Energy devices are equally effective in reducing thyroidectomy operative times, with no differences in the duration of surgery, drainage, or adverse events. Use of the UCSD was associated with higher postoperative pain scores, but was favored by the surgeons, likely due to the ability to perform fine dissection with the device itself.

The effect of parathyroidectomy on patients' symptoms in tertiary hyperparathyroidism.

BACKGROUND: The efficacy of parathyroidectomy for primary and secondary hyperparathyroidism is well-established but evidence in tertiary hyperparathyroidism is lacking. We examined parathyroidectomy's effect in tertiary hyperparathyroidism. METHODS: Patients with tertiary hyperparathyroidism who underwent parathyroidectomy were followed up for 12 months. A modification of the 13-item parathyroid symptoms list developed by Pasieka was administered at 0, 1, 3, 6, and 12 months post-surgery. We also examined if preoperative factors would predict symptom improvement post-surgery. RESULTS: Ninety-one patients were included. Survey response rates at 1, 3, 6, and 12 months post-surgery were 97.8%, 90.1%, 82.4%, and 80.2%, respectively. Mean preoperative Pasieka parathyroid score (PSS) was 6.3 ± 2.7. At first month, PSS decreased to 2.9 ± 2.0 (P < .001) and was sustained at 3, 6, and 12 months (2.7 ± 2.1, P < .001, 2.3 ± 1.6, P < .001 and 3.4 ± 2.5, P < .001). The degree of PSS reduction at 1-month post-parathyroidectomy correlated strongly with preoperative symptom severity (Pearson's coefficient: 0.690, P < .001). CONCLUSIONS: Parathyroid symptoms unequivocally improve post-parathyroidectomy. The greatest degree of improvement was observed in early postoperative period up to 6 months.

Correction: Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome.

[This corrects the article DOI: 10.18632/oncotarget.15720.].

Comparison of Outcomes of Fasciocutaneous Free Flaps and Jejunal Free Flaps in Pharyngolaryngoesophageal Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: The literature reports a wide variety of reconstructive methods for pharyngolaryngoesophageal (PLO) defects, the most widely used being anterolateral thigh (ALT), radial forearm (RFF), and jejunal free flaps (JFF). However, there is a lack of uniform agreement among head and neck surgeons as to which technique offers the best results. With an increasing number of salvage PLO extirpations, determining the role of radiotherapy in influencing postoperative complication rates is becoming ever more important. Hence, this study aims to provide an up-to-date comparison of surgical and functional outcomes of the fasciocutaneous ALT and RFF versus the intestinal JFF for circumferential and partial PLO defects and determine whether radiotherapy, both preoperative and postoperative, influences the postoperative fistula and stricture rates in circumferential defects. METHODS: A systematic review and meta-analysis were performed using PubMed for reports published in the most recent 10 years between 2007 and 2017. RESULTS: A total of 33 articles comprising 1213 patients were reviewed. For circumferential defects, fistula and stricture rates were significantly lower in JFF than ALT and RFF. Of note, there was no statistical difference in tracheoesophageal speech and oral alimentation rates between JFF and the FC flaps. For near-circumferential and partial defects, ALT has a significantly lower fistula rate than RFF. There was no statistical difference in stricture and oral alimentation rates between ALT and RFF [corrected]. Fistula rates were significantly higher in patients who had preoperative radiotherapy than those without. However, there was no significant difference in fistula and stricture rates for postoperative radiotherapy. CONCLUSIONS: Jejunal free flaps still remain an excellent first choice for PLO reconstruction of circumferential defects. For near-circumferential and partial defects, ALT seems to have a better performance than RFF. Preoperative radiotherapy was associated with an increased risk of fistula formation in circumferential PLO defects but not postoperative radiotherapy.

Elderly Patients with Advanced Head and Neck Carcinoma: Does Aggressive Treatment Result in Better Outcomes?

OBJECTIVE: There are no well-defined treatment recommendations for elderly patients with advanced head and neck squamous cell carcinoma. This study aimed to investigate whether aggressive treatment among the elderly translated into better survival outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary institution. SUBJECTS AND METHODS: Elderly patients (≥60 years) with advanced-stage head and neck squamous cell carcinoma (stage III and IV) treated between January 1991 and May 2014 were reviewed. According to current National Comprehensive Cancer Network guidelines, they were classified to have received standard or substandard treatment. Overall survival (OS), locoregional recurrence-free survival, and distant recurrence-free survival were evaluated. RESULTS: A total of 355 patients were treated curatively: 194 with up-front surgery and 161 with radiotherapy or concurrent chemotherapy and radiotherapy. Median OS was higher among patients who received standard treatment (42.0 vs 16.0 months, P < .001). On multivariate analysis, standard treatment showed superior OS ( P < .001). Use of substandard treatment showed a hazard ratio of 2.09 (95% CI, 1.59-2.74) for poorer OS. CONCLUSION: Aggressive standard treatment protocols should be advocated for elderly patients, where comorbidities permit, as they confer better outcomes.

A three gene immunohistochemical panel serves as an adjunct to clinical staging of patients with head and neck cancer.

BACKGROUND: Current management of head and neck squamous cell carcinoma (HNSCC) depends on tumor staging. Despite refinements in clinical staging algorithms, outcomes remain unchanged for the last two decades. In this study, we set out to identify a small, clinically applicable molecular panel to aid prognostication of patients with HNSCC. MATERIALS AND METHODS: Data from The Cancer Genome Atlas (TCGA) was used to derive copy number aberrations and expression changes to identify putative prognostic genes. To account for cross entity relevance of the biomarkers, HNSCC (n = 276), breast (n = 808) and lung cancer (n = 282) datasets were used to identify robust and reproducible markers with prognostic potential. Validation was performed using immunohistochemistry (IHC) on tissue microarrays of an independent cohort of HNSCC (n = 333). FINDINGS: Using GISTIC algorithm together with gene expression analysis, we identified six putative prognostic genes in at least two out of three cancers analyzed, of which four were successfully optimized for automated IHC. Of these, three were successfully validated; each molecular target being significantly prognostic on univariate analysis. Patients were differentially segregated into four prognostic groups based on the number of genes dysregulated (p < 0.001). The IHC panel remained an independent predictor of survival after adjusting for known survival covariates including clinical staging criteria in a multivariate Cox regression model (p < 0.001). . INTERPRETATION: We have identified and validated a clinically applicable IHC biomarker panel that is independently associated with overall survival. This panel is readily applicable, serving as a useful adjunct to current staging systems and provides novel targets for future therapeutic strategies.

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma.

Thyroid carcinoma usually presents as a neck lump. Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma (WDTC) is rare and little is known about these patients. The aim of this study is to characterize patients who present with distant metastasis as the sole initial manifestation of WDTC. Retrospective review of case records of WDTC seen at the National Cancer Centre Singapore from 2002 to 2015 was performed. Patients with no prior complaint of neck swelling and whose first presentation was distant metastatic WDTC were included. Patient demographics, disease characteristics, radiological imaging, histopathology, types of treatment administered, and survival outcomes were examined. Nineteen out of seven hundred and thirty-two cases fulfilled inclusion criteria. Mean age was 65.4 years. All patients presented with osseous (36.8%), pulmonary (31.6%), cerebral metastases (5.3%), or a combination of two out of three aforementioned sites (26.3%). Follicular thyroid carcinoma was most common (47.4%), followed by papillary (36.8%) and medullary (15.8%). More than two-thirds of patients had multiple metastatic foci. Thirteen out of nineteen patients (68.4%) underwent total thyroidectomy with or without neck dissection and adjuvant RAI, while the rest declined surgery. The mean length of follow-up was 40.1 ± 5.1 months and 5-year disease-specific survival was 48.0 ± 17.2%. Distant metastasis without a history of neck swelling as the initial presentation of WDTC is extremely rare. Osseous metastasis and follicular thyroid carcinoma are the most common metastatic site and etiology, respectively. Disease-specific survival at 5-year post-diagnosis is lower compared to patients with thyroid carcinoma diagnosed with distant metastasis on further work-up.

Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome.

Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that can be light-activated to eradicate tumors via direct cytotoxicity, damage to tumor vasculature and stimulating the body's immune system. Treatment outcome may vary between individuals even under the same regime; therefore a non-invasive tumor response monitoring system will be useful for personalization of the treatment protocol. We present the combined use of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of tumor response. The relative tissue oxygen saturation (rStO2) and relative blood flow (rBF) in tumors were measured using DOS and DCS respectively before and after PDT with reference to baseline values in a mouse model. In complete responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3 h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these parameters to baseline values was observed around 2 weeks after PDT. In partial responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast, the rStO2 and rBF readings in control tumors showed fluctuations above the baseline values within the first 48 h. Therefore tumor response can be predicted at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post-PDT corresponded to long-term tumor control. Diffuse optical measurements can thus facilitate early assessment of tumor response. This approach can enable physicians to personalize PDT treatment regimens for best outcomes.

Salivary fistula: Blue dye testing as part of an algorithm for early diagnosis.

Objective: Orocutaneous and pharyngocutaneous fistula (OPCF) is a debilitating complication of head and neck surgery for squamous cell carcinoma (SCC), resulting in delayed adjuvant treatment and prolonged hospitalization. As yet, there is no established test that can help in prompt and accurate diagnosis of OPCF. This study aims to determine the accuracy of bedside blue dye testing and its role as part of an algorithm for early diagnosis. We also analyze the risk factors predisposing to OPCF. Study Design: Retrospective cohort study from 2012 to 2014. Methods: Patients with head and neck SCC who underwent major resection and reconstruction, at risk of OPCF, were included. Results of blue-dye and video-fluoroscopic swallow-studies (VFSS) testing for OPCF were recorded. For the patients that were noted to develop OPCF, the length of time to diagnosis of fistula and subsequent mode of management were examined. Results: Of the 93 patients in this study, 25 (26.9%) developed OPCF. Advanced T-classification (T3/T4) was the only significant predisposing risk factor (p = 0.013). The sensitivity and specificity of the bedside blue dye testing was found to be 36.4% and 100%, respectively. The test positive patients were diagnosed with OPCF at a median of postoperative day (POD) 9.5 as compared to POD 13 for the test negative patients (p = 0.001). Early diagnosis was associated with faster fistula resolution with treatment. Conclusion: Blue dye testing is a simple bedside test that can assist in the early diagnosis of OPCF in patients, allowing treatment to be instituted earlier with improved outcomes. Level of Evidence: 3.