Thomas Shpitzer

Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile.

Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which induce oxidative and nitrative stress, are main contributors to oral carcinogenesis. The RNS (nitrosamines: nitrates, NO3, and nitrites, NO2) are also produced by the reaction of ROS and other free radicals with nitric oxide (NO) and are therefore in equilibrium with it.

Concomitant Analysis of Salivary Tumor Markers—A New Diagnostic Tool for Oral Cancer

Purpose: Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients. Experimental Design: We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients. Results: Significant increases (of 400%) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively. Conclusions: The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.

The free iliac crest and fibula flaps in vascularized oromandibular reconstruction: comparison and long-term evaluation.

A variety of free flaps have been successfully used for mandible reconstruction. This study compared the short‐ and long‐term results of using the free iliac crest and fibula flaps.

Free fibula long bone reconstruction in orthopedic oncology: a surgical algorithm for reconstructive options.

The fibula free flap became popular in orthopedic oncology for limb-sparing long bone tumor resection. It is particularly suitable for intercalary or resection arthrodesis options. In the present series, a surgical reconstruction algorithm was used, enabling each patient to receive a personalized technique. During the years 1998 to 2002, 30 patients underwent limb-sparing surgery for long bone sarcoma. There were 18 males and 12 females. Their mean age was 23 years (range, 9 to 70 years). The diagnoses were Ewings sarcoma (11 patients), osteogenic sarcoma (eight patients), chondrosarcoma (five patients), giant cell tumor of bone (three patients), high-grade soft-tissue sarcoma (two patients), and leiomyosarcoma of bone (one patient). The majority of tumors where located in the lower extremity (23 patients), mostly in the femur (15 patients with four tumors in the proximal femoral shaft, five tumors in the distal femoral shaft, five tumors in the whole femoral shaft, and one tumor in the proximal femoral head). In seven patients, the upper extremity was involved; in six patients, the radius was involved; and in one patient, the humerus was involved. The free fibula flap was used in three types of approaches: vascularized fibula as an osseous flap only (18 patients), a combination of a vascularized fibula flap in conjunction with an allo-graft (Capannas technique; 10 patients), and a free double-barreled fibula (two patients). All flaps survived. Postoperatively, all patients were monitored clinically, radiologically, and by radioisotope bone scan studies. Callus formation and union were shown 2.6 to 8 months postoperatively. Patients who underwent lower extremity reconstruction were nonweightbearing for 3 to 9 months, with a transition period in which they used a brace and gradually increased weightbearing until full weightbearing was achieved. Eight patients had 11 recipient-site complications. Two patients (6.7 percent) had hematomas, and three patients (10 percent) had infection and dehiscence of the surgical wound with bone exposure in one patient; all complications resolved with conservative treatment only. Failure of the hardware fixation system occurred in two patients, mandating surgical correction. No fibula donor-site complications were recorded. In intercalary resections, the use of the vascularized fibula flap as an isolated osseous flap might be insufficient. Different body sites have different stress loads to carry, depending on the age of the patient and on his individual physical status. To achieve initial strength in the early period, the authors combined the free fibula flap with an allograft (Capannas method) or augmented it as a double-barreled fibula. They propose a surgical algorithm to assist the surgeon with the preferred method for reconstruction of various long bone defects in different body locations at childhood or adulthood. Long bone reconstruction using a vascularized fibula flap, alone or in combination with an allograft, autogenous bone graft, or double-barreled fibula for limb-sparing surgery, is a safe and reliable method with a predictable bony union, good functional outcome, and a low complication rate.

Leg morbidity and function following fibular free flap harvest

Over a period of 3 years, 50 consecutive free fibular flaps for mandibular reconstruction were performed on 47 patients. In 38 patients (81%) a skin paddle was included with the flap to provide either mucosal lining or skin cover; in 9 patients (19%) bone alone was used. Thirty-one patients (66%) required a skin graft to close the donor defect in the leg. Donor leg morbidity and function were determined by patient questionnaire and by physical examination. Forty-one donor sites in 40 patients were available for long-term follow-up. The follow-up ranged from 4 to 39 months with an average of 17 months. Immediate postoperative infection occurred in the donor site of 1 patient (2%) and required additional surgery. There was no other immediate donor site complications when closure required skin grafting. Eleven patients (27%) had late donor site morbidity, consisting of motor weakness of the great toe in 5 patients, ankle instability and/or stiffness in 3 patients, donor site pain in 1 patient, and edema in 2 patients. All complications were graded as mild in severity by the patient and by the examiner. In this series, although most donor site defects required skin grafting, short- and long-term morbidity was minimal. After a short rehabilitation period, all patients were fully able to engage in all daily and recreational activities.

Salivary analysis of oral cancer biomarkers

Background:Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing.Methods:We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death.Results:Five markers increased in cancer patients by 39–246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (P⩽0.01). Three markers decreased by 16–29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (P⩽0.01). Increase in salivary carbonyls was profound (by 246%, P=0.012); alterations in CycD1 (87% increase, P=0.000006) and Maspin (29% decrease, P=0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively.Conclusion:The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

Squamous cell carcinoma of the oral tongue in young patients.

Objectives/Hypothesis: Cancer of the tongue is reported with increasing frequency in young people. The objective of this work was to study the biologic and clinical course of the disease in this group. The clinical course of the disease in this patient group remains controversial.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.Methods:The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.Results:The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.Conclusion:This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Laryngeal and hypopharyngeal obstruction in sleep disordered breathing patients, evaluated by sleep endoscopy

The objectives of our study were to demonstrate the patterns and sites of the upper airway (UA) collapse in obstructive sleep apnea/hypopnea syndrome (OSAHS) patients, utilizing the sleep endoscopy technique, and to describe the technique and summarize our experience in a large series of patients. UA findings during sleep endoscopy with midazolam were examined prospectively in 55 surgical candidates with OSAHS. The uvulopalantine was the most common site of obstruction (89%), followed by the tongue base, hypopharynx and larynx (33% each), and nose (21%); 72% of the patients had multiple obstructions. There was a significant correlation between the number of obstructions and the respiratory distress index (RDI). Laryngeal obstruction was typically supraglottic. Hypopharyngeal obstruction involved concentric UA narrowing. Our findings emphasize the considerable rate of laryngeal and hypopharyngeal obstructions in patients with OSAHS and suggest that their misdiagnosis may explain at least part of the high surgical failure rate of UPPP for OSAHS patients. The number of obstruction sites correlates with respiratory distress index. Sleep endoscopy is safe and simple to perform.

Preoperative evaluation of patients with parathyroid adenoma: Role of high-resolution ultrasonography†

Unilateral parathyroid exploration with adenoma removal and identification of a normal parathyroid gland is a controversial surgical approach to the treatment of primary hyperparathyroidism. The aim of this study was to evaluate the ability of high‐resolution ultrasonography to localize adenomas preoperatively and to assess the effect of such localization on operative time.