Michael P. Hier

Advances and applications of oral cancer basic research.

Cancer of the oral cavity accounts for almost 3% of cancer cases in the world. The incidence varies widely reflecting geographic differences in exposure to risk factors. The recent rise in younger age groups and females seen in many countries is of particular concern. Treatment and management of complications, locoregional recurrence and further primary tumors result in high morbidity and mortality especially when the disease is advanced stage at initial diagnosis. Progress in cancer research has provided abundant new knowledge about cellular processes and molecular biology underlying oral carcinogenesis and tumor progression. The present review attempts to summarize the current most widely-used research approaches and their application in the prevention, diagnosis, effective treatment, and improved outcome of oral cancer.

Same-day discharge after total thyroidectomy: the value of 6-hour serum parathyroid hormone and calcium levels.

The purpose of this study was to determine whether patients who undergo total thyroidectomy will have postoperative hypocalcemia develop when they reach the critical 6‐hour serum levels defined as parathyroid hormone (PTH) ≥28 ng/L and simultaneous corrected calcium ≥2.14 mmol/L.

Predicting Calcium Status Post Thyroidectomy with Early Calcium Levels

OBJECTIVE: The study goals were to predict postoperative normocalcemia and hypocalcemia after total thyroidectomy using calcium levels and to assess the value of a standardized protocol in managing the total thyroidectomy patient. STUDY DESIGN: We conducted a prospective study encompassing 68 patients undergoing a total thyroidectomy using a standardized protocol. Blood to measure postoperative calcium levels was drawn at 6, 12, and 20 hours and then twice daily thereafter. Calcium slope was calculated from the 6- and 12-hour serum corrected calcium levels. RESULTS: Logistic regression analysis allowed the comparison of the 6- and 12-hour calcium slope versus proportion of normocalcemic patients postoperatively. A slope of +0.02 had a 97% chance of remaining normocalcemic (p = 0.0007). CONCLUSION: Successful prediction of calcium status post total thyroidectomy can be achieved using the slope of the 6- and 12-hour calcium levels. The risk of developing severe hypocalcemia can also be predicted with these slope values. Implementation of the protocol resulted in a significant reduction in the duration of hospital stay for patients who remain normocalcemic.

Systemic inflammatory markers as independent prognosticators of head and neck squamous cell carcinoma.

The purpose of this study was to investigate the prognostic value of the pretreatment inflammatory markers platelet‐to‐lymphocyte ratio (PLR) and the neutrophil‐to‐lymphocyte ratio (NLR) in patients with head and neck squamous cell carcinoma (HNSCC).

Phase III randomized study: Oral pilocarpine versus submandibular salivary gland transfer protocol for the management of radiation-induced xerostomia

Xerostomia is a serious morbidity of radiation treatment in head and neck cancer.

Postoperative parathyroid hormone level as a predictor of post-thyroidectomy hypocalcemia.

OBJECTIVES To evaluate levels of parathyroid hormone following total thyroidectomy in order to ascertain its ability to predict postoperative hypocalcemia. To establish standardized criteria permitting the safe discharge of total thyroidectomy patients within 13 hours of surgery. METHODS This is a prospective study in which parathyroid hormone levels were tested in 54 consecutive patients who underwent total thyroidectomy. Levels were measured postoperatively at 6, 12, and 20 hours. Corrected calcium levels were also measured at 6, 12, and 20 hours in accordance with the preexisting protocol. RESULTS Statistical analysis demonstrates that patients with corrected calcium levels greater than or equal to 2.14 mmol/L and parathyroid hormone levels greater than or equal to 28 ng/L at 12 hours post-thyroidectomy can be discharged without further need for calcium monitoring. The analysis also demonstrates that patients with 12-hour parathyroid hormone levels less than or equal to 20 ng/L are at significant risk of developing hypocalcemia. CONCLUSION Parathyroid hormone levels in conjunction with corrected calcium values are accurate predictors of the calcium trends of post-thyroidectomy patients. Implementation of this protocol can result in shorter hospital stays for the majority of post-thyroidectomy patients, which can translate into substantial cost savings for the health care system.

Benefits Resulting from 1-and 6-Hour Parathyroid Hormone and Calcium Levels After Thyroidectomy

OBJECTIVE: Previous studies have established the efficacy of post-thyroidectomy hypocalcemia monitoring using parathyroid hormone (PTH) and corrected calcium levels at 1 and 6 hours. The goal of this study was to measure the impact of managing patients based on the above findings with respect to: duration of hospital stays, rates of transient hypocalcemia, number of blood tests, cost savings, and discharge from the hospital as early as 8 hours post-thyroidectomy without compromising safety. STUDY DESIGN AND SETTING: This is a prospective study involving 95 total thyroidectomy patients using historical data as controls. The previous protocol was modified in that all blood tests ceased for patients meeting the 6-hour critical level of PTH ≥ 28 ng/L and simultaneous corrected calcium ≥ 2.14 mmol/L (8.56 mg/dL). Furthermore, patients with 1-hour PTH levels ≤ 8 ng/L were prophylactically treated with calcium and vitamin D supplementation. RESULTS: This study demonstrates lower rates of transient hypocalcemia from 28% to 9% (OR = 4.13, P = 0.016), a 10-hour reduction in mean hospital stay, and fewer blood tests (23 vs 15) for patients undergoing total thyroidectomy since the implementation of the new protocol. Furthermore, the experimental protocol resulted in an average cost savings of

High prevalence of obstructive sleep apnea among patients with head and neck cancer.

766 per patient. CONCLUSIONS: The new algorithm resulting from PTH and corrected calcium monitoring at 1 and 6 hours post-thyroidectomy has led to significant cost savings for our institution. It has also translated into greater patient satisfaction as a result of fewer blood tests, a lower incidence of transient hypocalcemia, and significantly shorter hospital stays.

Recurrent Oral Cancer: Current and Emerging Therapeutic Approaches

OBJECTIVES To determine the prevalence of obstructive sleep apnea (OSA) in patients with cancer of the oral cavity and oropharynx scheduled for primary surgical resection. To correlate the presence of OSA and the occurrence of postoperative morbidities in this patient population. METHODS This was a prospective study involving 17 patients with malignancies of the oral cavity and oropharynx scheduled for primary surgical resection. Consecutive patients were approached to undergo overnight polysomnography to determine the apnea-hypopnea index (AHI). OSA was defined by an AHI value > or = 20 events per hour. Postoperative morbidities were evaluated in a blinded fashion for the patients completing surgery. RESULTS OSA was present in 13 of 17 patients, yielding a striking prevalence of 76% in this patient group. The mean AHI for patients with OSA was 44.7 +/- 3.5 (standard error) events per hour, with a mean nadir oxygen saturation of 88.2 +/- 1.8%, consistent with moderate to severe sleep-disordered breathing. The OSA and non-OSA patients were similar with respect to age and body mass index. The mean size of the primary tumour was 3.3 cm in patients with an AHI < 20 and 3.5 cm in those with an AHI > or = 20 (p = not significant). Overall, postoperative complications, defined as prolonged intensive care unit stay (> 24 hours), need for mechanical ventilation, and cardiopulmonary morbidities, were observed in 67% of OSA and 25% of non-OSA patients. CONCLUSIONS These findings point to a strong association between OSA and malignancies of the oral cavity and oropharynx. This relationship was independent of the size of the primary malignancy in this patient population with tumours ranging from 1 to 7 cm (p = not significant). When comparing the two groups (AHI < 20 and AHI > or = 20), there was a tendency for the group with OSA to have an increase in postoperative morbidities. Further research is warranted to further evaluate the postoperative morbidities and mortalities associated with OSA in this patient population and to determine the potential roles for preoperative treatment with continuous positive airway pressure and tracheotomy.

Incidence and histopathological behavior of papillary microcarcinomas: Study of 429 cases

Oral cavity cancer (OCC) is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.