Relationship between age, comorbidities and complications in head and neck cancer patients undergoing curative surgery.

BACKGROUND: Both age and comorbidity are accepted as significant prognostic factors for adverse perioperative outcomes in major surgery. Elderly patients may be overlooked for radical treatment for fear of poor perioperative outcome. We aim to assess the relationship between age, comorbidities and post-operative outcomes in a tertiary head and neck unit. METHODS: A retrospective analysis was undertaken on 651 patients who underwent surgery for head and neck cancer at a tertiary hospital between 2007 and 2014. RESULTS: A total of 253 (38.9%) patients were aged ≥70 years and 398 (61.1%) patients were ≤69 years. Age alone did not predict prolonged post-operative stay, perioperative complications nor perioperative mortality. Congestive cardiac failure and/or complicated diabetes were significantly associated with poor outcomes, as was male sex. CONCLUSION: Patients of any age with cardiac failure or complicated diabetes have a higher rate of post-operative complications in head and neck surgery.

Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.

The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia.

This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.

Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer.

Noninvasive localized measurement of extracellular pH in cancer tissues can have a significant impact on the management of cancer. Despite its significance, there are limited approaches for rapid and noninvasive measurement of local pH in a clinical environment. In this study, we demonstrate the potential of noninvasive topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated with Alexa Fluor(®) 647) to image changes in extracellular pH associated with head and neck squamous cell carcinoma using widefield and high resolution imaging. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact fresh human tissue specimens using widefield and high-resolution fluorescence imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered throughout the epithelium of intact tissues with a depth exceeding 700 µm. Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast increased four to eight fold higher in clinically abnormal tissues as compared to paired clinically normal biopsies. Furthermore, the imaging approach showed significant differences in fluorescence contrast between the cancer and the normal biopsies across diverse patients and different anatomical sites (unpaired comparison). The fluorescence contrast differences between clinically abnormal and normal tissues were in agreement with the pathologic evaluation. Topical application of fluorescently labeled pHLIP can detect and differentiate normal from cancerous tissues using both widefield and high resolution imaging. This technology will provide an effective tool to assess tumor margins during surgery and improve detection and prognosis of head and neck cancer.

Prospective comparison of routine and selective operative cholangiography.

BACKGROUND: In a rural centre with limited resources and no endoscopic retrograde cholangiopancreatography facilities, a prospective cohort study was established to compare policies of routine and selective intraoperative cholangiography (IOC) in order to develop a local protocol. METHODS: Patients undergoing laparoscopic cholecystectomy from 1 February 1995 to 30 November 2002 were allocated to undergo routine or selective IOC according to birth date. Those with known common bile duct (CBD) stones were excluded. Selective IOC was performed on the basis of abnormal liver function tests or a dilated CBD on ultrasound. Study end points after 12 months follow-up were retained CBD stones, CBD injury, operating times and the effect of IOC on the management of patients with persistent biliary symptoms postoperatively. RESULTS: Of the 148 patients in the routine group, 94 underwent IOC and CBD stones were shown in 12. Of the 155 in the selective group, IOC was performed in 34 of 45 eligible patients and stones were shown in five. Sixteen patients re-presented with recurrent biliary symptoms or jaundice postoperatively and eight had proven retained CBD stones, of whom only one had undergone (false-negative) IOC. There was no significant difference in mean operating time (56 vs 61 min; t-test P = 0.15). There was one CBD injury in each group, both incurred after successful IOC. CONCLUSIONS: There was no difference between policies of routine or selective IOC in relation to operating times, retained CBD stone rates or CBD injury. However, the authors found management of patients with recurrent biliary symptoms easier if an IOC had been performed, and IOC was easier to perform when the staff were expecting it. Thus a policy of routine IOC has been adopted.