The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review.

Objective: Studies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known. Design: A retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases. Results: Increased alveolar bone loss, OR = 4.302 (2.510 - 7.376), fewer missing teeth, OR = 0.897 (0.835-0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146- 4.174) was significantly associated with hospitalization. Conclusions: Alveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.

[On-pump total arterial revascularization in coronary artery disease patients with left ventricular dysfunction: a multi-center retrospective study].

Objective: To evaluate the clinical outcomes of on-pump total arterial revascularization with bilateral radial artery (BRA) and left internal mammary artery (LIMA) as conduits in coronary artery bypass grafting (CABG) patients with left ventricular dysfunction (LVD). Methods: All the perioperative medical records and follow-up results of coronary artery disease patients with left ventricular ejection fraction (LVEF) ≤ 40% undergoing CABG from 24 heart centers of 15 provinces and autonomous regions in China between July 2015 and December 2019 were retrospectively analyzed. Results: A total of 87 consecutive patients (55 males and 32 females) underwent on-pump CABG with BRA and LIMA, with a mean age of (57.5±9.1) years old. There were 22 patients complicated with primary hypertension, 12 with diabetes mellitus, 8 with peripheral vascular disease, 7 with chronic obstructive lung disease, 12 with mild renal injury and 3 with partial aortic calcification. There were 43 cases with in-stent stenosis, and 21 had left main disease. The mean LVEF and left ventricular end-diastolic diameter (LVEDD) was (35.5±7.3)% and (65.5±2.6) mm, respectively. The mean graft number, aortic cross-clamp time and cardiopulmonary bypass duration was 3.2±0.9, (90.5±22.7) min and (113.4±19.2) min, respectively. There were 32 mitral and 9 aortic valve replacements, and 5 tricuspid annuloplasties. Prophylactic intra-aortic balloon pumps were implanted in 27 patients. There were 2 operative deaths from acute heart failure. After surgery, there were 15 cases of atrial fibrillation, 1 case of acute kidney injury, 1 case of acute myocardial infarction, and 1 cases of stroke. All the patients fulfilled the follow-up, with a mean time of (39.5±7.7) months. At 3 months after surgery, LVEDD was decreased and LVEF was improved significantly compared with pre-operative indicators [(53.0±1.5) mm vs (65.5±2.6) mm, t=9.51 P=0.02; (45.2±3.3)% vs (35.5±7.3)%, t=13.79, P=0.001]. No major cardiac events were reported during the follow-up. At (30.5±7.4) months after surgery, 62.4% of patients (53/85) underwent coronary CT angiography examination, and the results indicated that the graft patency was 98.8%, with only one case of RA occlusion occurred. Conclusion: In selected patients of LVD, on-pump total arterial revascularization with BRA and LIMA conduits was proved to be safe and effective.

[Mid-term multi-center outcomes of bilateral radial artery as conduits in coronary artery bypass grafting].

Objective: To evaluate the mid-term outcomes of bilateral radial artery (BRA) grafts in coronary artery bypass grafting (CABG). Methods: All perioperative medical records and follow-up results of CABG with BRA grafts in multi-centers of China were analyzed retrospectively. Results: A total of 211 patients (170 males and 41 females) underwent CABG grafting with BRA conduits between August 2013 and September 2018, with a mean age of (56.5±9.7) years old (rang 41 to 73 years). There were 161 cases of triple-vessel disease and 50 cases of two-vessel disease. Ninety patients had diabetes mellitus (DM), 35 patients with peripheral vascular disease, 4 patients with chronic obstructive pulmonary disease and 11 with heart valve disease. Two patients underwent off-pump CABG and 209 patients accepted on-pump CABG with commitment valve surgery. There were 210 cases of total arterial revascularization and 161 cases using left thoracic artery conduits, with a graft number of 2-4 (2.7±0.9). No operation-related death occurred, atrial fibrillation happened in 12 patients, hemothorax in 7 cases, and forearm hematoma in one case, hypoxemia in 13 cases and pneumonia in one case. The duration of mechanical ventilation was (8.3±4.7) hours and the mean hospital length of stay was (7.1±2.9) days. Follow-up was completed in 191 patients (90.52%) with a duration of 3-59 (35.5±9.3) months. The mean left ventricular ejection fraction at 3 months after operation was significantly improved, compared to that of the pre-operation (61.0%±7.2% vs 47.1%±5.3%, P=0.017). All patients survived, except that one died from brain injury. No major cardiac events occurred, with a cumulative survival rate of 100% at 1 year and 99.53% at 3 year after operation, respectively. It was showed in coronary CT angiography (CTA) examination that all grafts in 132 patients were patent at the mean follow-up duration of (21.5±6.4) months. Conclusions: BRA grafts as arterial conduit in CABG are proved to be safe, easy for total arterial revascularization and have good mid-term clinical results.

[An analysis of electrocochleography in patients with OSAHS].

Objective:To investigate the values of electrocochleograph（ECochG）in patients with OSAHS. Method:ECochG was performed in 31 (62 ears) OSAHS patients (moderately 5 cases, severely 26 cases) and 28 healthy adults (56 ears). AP latency ，AP amplitude and SP/AP were measured and analyzed. Result:There was no difference between the two groups in SP/AP amplitude ratio（P>0.05） while both AP latency（P<0.05） and AP amplitude（P<0.05） were significantly different. Conclusion:ECochG can confirm the damage of cochlear and auditory nerve near the cochlear segment in patients with moderate to severe OSAHS.

The relationship between number and function of EPCs and concentration of VEGF165 and SDF-1 in coronary artery spasm.

OBJECTIVE: We aimed at investigating the functions of endothelial progenitor cells (EPCs) in the pathophysiology of coronary artery spasm (CAS) and coronary artery disease (CAD), as well as to evaluate the correlation of these diseases with the number and function of EPCs, the plasma concentration of vascular endothelial growth factor 165 (VEGF165) and stromal cell-derived factor 1 (SDF-1). PATIENTS AND METHODS: Participants were recruited into three groups, CAS, CAD and the control. The number and functions of early EPCs and outgrowth endothelial cells (OECs) were determined in peripheral blood samples, and the endothelial function was evaluated by measuring endothelium-dependent flow-mediated vasodilation (FMD). RESULTS: No differences of baseline characteristics were found among CAS, CAD, and the control groups. The OECs isolated from CAS and CAD exhibited significant decrease in the percentage of CD34+/CD45- population, OEC colony formation, OEC proliferation and OEC tubulogenesis, nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) activity, and the phosphorylation level at Ser1177 of eNOS, compared with OECs isolated from control participants. Meanwhile, FMD was significantly reduced in CAS and CAD (CAS, 4.1% ± 1.9%; CAD, 4.3% ± 1.8%; control, 11.2% ± 3.5%). FMD was positively correlated to OEC functions including NO production, eNOS phosphorylation, colony formation, and proliferation. No differences of plasma VEGF165 and SDF-1 concentrations were recorded among these three groups. Similarly, there was no correlation between plasma VEGF165 (and SDF-1) concentration and EPC number and function. CONCLUSIONS: EPCs show the potential of repairing damaged endothelium in CAS and CAD.

Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation.

BACKGROUND: To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro. METHODS: Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K+, Na+, Cl-, blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods. Renal cortex were harvested at 6 hours for the following measurement: lactic acid (LD), adenosine triphosphate (ATP), malondialdehyde (MDA), neutrophil accumulation (MPO), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß). Ischemia-induced apoptosis and the protein expression levels of total Akt, phospho-Akt, total Erk, and phospho-Erk were analyzed by Western blotting. RESULTS: Almost all of the tested metabolites in preservation solutions were reduced with time in the HMP group. Levels of Na+, Cl-, BUN, Cr, K+, and LDH were lower in the HMP group compared with the SCS group, with differences in the first 4 reaching statistical significance. HMP alleviated ATP degradation and LD accumulation, diminished the MDA (P < .05) and MPO (P = .227) levels, and greatly raised IL-10 and TGF-ß (P < .05) expression. A marked decrease of proapoptotic and a large increase of antiapoptotic markers (P < .05) along with greatly raised Akt (P < .05) and Erk (P < .01) phosphorylation was observed in the kidney of the HMP group compared with the SCS group. CONCLUSION: HMP's kidney graft protection involves inhibition of accumulation of toxic metabolites, oxidative damage, and apoptosis along with upregulation of the Akt and Erk signaling pathway.

Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERß) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERß signaling in mediating DOL effects in male mice to further decipher sex differences. METHODS: Male 21 day-old WT and ERßKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. RESULTS: ERßKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. CONCLUSIONS: The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.

[Necessity of repeated roll test in horizontal semicircular canalithasis positioned diagnosis].

OBJECTIVE: To investigate the influence of repeated roll test in horizontal semicircular canalithasis(HSC-Can) positioned diagnosis, so as to investigate the cecessity of repeated roll test. METHODS: The patients with a chief complaint of positional vertigo accepted two consecutive cycles roll test, the evoked nystagmus characteristics of each cycle recorded by video-nystagmuograph(VNG), whose direction, intensity, time and other parameters characteristics were analyzed in 51 HSC-Can. RESULTS: Horizontal nystagmus in the same direction with turning were induced in HSC-Can roll test. In 51 HSC-Can, roll test cycle 1 and cycle 2 induced nystagmus same strength side in 26 cases(51.0%), of which 19 cases with stronger nystagmus intensity in cycle 2, another 7 cases were weaker; the opposite strength side of the two loops induced nystagmus, and cycle 1 evoked nystagmus intensity were weaker than cycle 2, based on cycle 2 results determined HSC-Can affected side in 25 cases (49.0%). Lesion and normal side in cycle 1 induced nystagmus duration (x±s, the same below) were (13.4±11.5)s and (14.1±9.9)s, respectively intensity (18.1±22.4)°/s and (13.0±12.0)°/s; as in cycle 2 induced nystagmus duration was (20.7±10.2)s and (18.0±12.0)s, strength respectively(40.4±28.0)°/s and (15.6 ±11.2)°/s. Cycle 2 ipsilateral rotor position evoked nystagmus showed longer duration and stronger intensity than cycle 1. Between two cycle induced ipsilateral nystagmus duration, intensity differences were statistically significant (t values were -4.233 and -5.154, P=0.000). 51 HSC-Can patients, 44 patients selected repositioning maneuver, after 1-2 times of maneuver, 41 cases (93.2%) showed complete resolution of symptoms, all cases's symptoms were improved; other 7 patients selected medication only. CONCLUSION: The proposed suspicious HSC-Can patients should receive at least two cycles roll test, and mainly in the second cycle could determine the location of the responsible semicircular canals.

Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells.

The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis.

[The evaluation of hearing aid effect in presbycusis].

Objective:To evaluate the effect of hearing aid in presbycusis. Method:Using the method of international outcome inventory for hearing aids(IOI-HA)and medium acoustic intensity(65 dBSPL) word recognition score(WRS), to evaluate the effect of hearing aid in moderate and severe presbycusis. Result:After the hearing aid of moderate presbycusis, The improved value of monosyllabic words and recognition rate in quite and noise statement(SNR=5) were 31.15%, 23.21%, 44.11%.However, improved values in severe presbycusis were 37.51%, 48.47%，50.17%, before and after hearing aid, the difference of the improved average value was statistically significant(P <0.05); Both the moderate and severe presbycusis were satisfacted with hearing aid.The IO-HA scores of moderate and severe presbycusis ranged from 15 to 34.The difference of IOIHA score of moderate and severe presbycusis had no statistical significance(P >0.05); moderate and severe presbycusis with high satisfaction with HA of quiet statement,and low satisfaction of monosyllabic words listening, and the degree of satisfaction was higher in patients with moderate to severe hearing loss in noise statement.Conclusion:Speech audiometry is an important method to assess the effect of hearing aid; IOI-HA is a timeconsuming short, subjective method.The combine of multiple evaluations have guiding significance to debugging of hearing aid expected effect and hearing aid device.

Living status in patients over 85 years of age after TUVRP.

INTRODUCTION: To evaluate surgical risk and post-operative quality of living status in patients over 85 years of age after transurethral vaporization resection of the prostate (TUVRP). METHODS: Sixty patients over 85 years of age underwent TUVRP were compared with 228 patients less than the age of 80 years. Group A was 60 patients greater than 85 years of age, Group B was 137 patients from 71 to 79 years of age, and Group C was 91 patients from 60 to 70 years of age. RESULTS: In Group A, pre-operative ASA grade was higher than the other two groups, compared with Group C, p < 0.01. Operating time was 40.03 ± 18.90 min, compared in the three groups, p > 0.05. Follow-up was obtained in 49 (81.67%) patients; of them 10 patients were deaths with a survival time of 22.90 ± 11.14 months. In the 39 survivors, post-operative IPSS score was 11.17 ± 6.9, compared with Group B, p > 0.05 and Group C, p < 0.01. Quality of Life (QOL) index was 1.11 ± 0.80, compared with Group B, p < 0.001 and Group C, p < 0.01. Barthel Index score in 16 patients was >60 and the score was 82.81 ± 8.56 pre-operatively. The patients with >60 were increased to 19 cases and the score was improved to 90.93 ± 7.58 (p < 0.001) in follow-up. CONCLUSION: Surgical risk in patients over 85 years of age was higher than patients less than the age of 80 years. A safety TUVRP could improve their voiding function and activities of daily living.

Effects of microwave radiation and conductive heating on Tribolium castaneum microstructure.

Microwave radiation and conductive heating were used to completely kill adult Tribolium castaneum (Coleoptera: Tenebrionidae) in wheat flour to protect the flour during storage without significantly effecting its quality. The microstructure of T. castaneum was analyzed to reveal the mechanisms leading to death under microwave and heat treatments. Microwave radiation and conductive heating had different effects on the microstructure of the cuticle of adult T. castaneum and on the ultrastructure of the cells of the epidermis, fat body, and midgut. Both treatments caused a large cavity to appear in the nucleus and the disappearance of mitochondria and the Golgi apparatus. After microwave treatment, there was little change in the surface microstructure but the epidermis was of uneven thickness and the four outer layers of the cuticle were thinner. Nuclear size was essentially unchanged, but fat body cells were fewer and coalesced together. In contrast, conductive heating led to a disordered arrangement of cells on the surface of T. castaneum and indistinct boundaries between layers of the cuticle. The nuclei were enlarged and the fat body cells noticeably fewer and indistinct with a scattered distribution. Thus, microwave treatment produced less severe effects on the surface microstructure and cellular ultrastructure of T. castaneum than did conductive heating. It is concluded that these cellular and surface changes were responsible for the death of T. castaneum.

Activation of adenosine A2A receptor attenuates inflammatory response in a rat model of small-for-size liver transplantation.

OBJECTIVE: To investigate the effects of adenosine A2A receptor (A2AR) activation on inflammatory responses in small-for-size liver transplantation. MATERIALS AND METHODS: A rat orthotopic liver transplantation model was established using 35% grafts. Expression of A2AR in liver grafts was assessed using Western blot analysis. Recipients were given either saline solution (control group) or CGS21680 (A2AR agonist) or ZM241385 (A2AR antagonist) immediately after and 12 hours after reperfusion. Proinflammatory factors (tumor necrosis factor-alpha [TNF-alpha], macrophage inflammatory protein-2 [MIP-2], and intercellular adhesion molecule-1 [ICAM-1]) were analyzed using an enzyme-linked immunosorbent assay; neutrophil infiltration was assessed using a myeloperoxidase activity assay and hematoxylin-eosin staining; and nuclear factor-kappaB (NF-kappaB) was assessed using Western blot analysis and an electrophoretic mobility shift assay. RESULTS: Expression of A2AR was increased after reperfusion, peaking at 6 to 12 hours after transplantation. Compared with controls, A2AR activation decreased TNF-alpha, MIP-2, and ICAM-1 expression, reduced MIP-2 activity, inhibited IkappaB phosphorylation, and suppressed NF-kappaB activation. CONCLUSION: Expression of A2AR is increased after transplantation, and suppresses inflammatory responses by blocking NF-kappaB activation in small-for-size grafts.

Deep brain stimulation therapy for Parkinson's disease using frameless stereotaxy: comparison with frame-based surgery.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) surgery has been performed using frame-based stereotaxy traditionally; however, in recent years, it has also been performed using frameless stereotaxy. The purpose of this study was to compare the experience at our centre in performing DBS surgery using frameless surgery for patients with Parkinson's disease with that of using frame-based surgery. METHODS: Twenty-four patients with advanced Parkinson's disease underwent DBS surgery, 12 with frameless and 12 with frame-based stereotaxy. After identifying the subthalamus by microelectrode recording (MER), the DBS electrodes were implanted and connected to an implanted programmable generator in all patients. Programming was started 1 month after the operation and the outcome of the patients was followed up regularly for at least 12 months. RESULTS: After 1 year of follow-up, the patients who received frameless surgery showed no difference in the degree of improvement in clinical motor function compared with the patients who received frame-based surgery (P = 0.819); the average improvement was 60.9% and 56.9%, respectively, in the stimulation alone/medication-off state, as evaluated by the Unified Parkinson's Disease Rating Scale-III motor subscore. However, the frameless group had significantly shorter total MER time (P = 0.0127) and a smaller number of trajectories (P = 0.0096) than the frame-based group. CONCLUSIONS: Our data indicate that frameless DBS surgery has a similar outcome when compared with frame-based surgery; however, frameless surgery can decrease the operation time, MER time, and MER trajectory number.

Areca-treated fibroblasts enhance tumorigenesis of oral epithelial cells.

Several hundred million Asians chew areca nut, which is strongly associated with oral carcinogenesis in people of this region. The impacts of areca nut extract on oral target cells are largely unclear. This study hypothesized an inductive role for areca-nut-exposed stromal cells in the progression of oral carcinomas in an at-risk population. Oral fibroblasts with chronic subtoxic areca nut extract treatment exhibited growth arrest and MMP-2 activation. The supernatant of arrested oral fibroblasts activated the AKT signaling pathway in oral carcinoma cells. The enhancement of proliferation, migration, and anchorage-independent growth of oral carcinoma cells elicited by such supernatant could be abrogated by blockers against MMP-2 or AKT. Subcutaneous co-injection of arrested oral fibroblasts into nude mice significantly enhanced the tumorigenicity of xenographic oral carcinoma cells. This study concludes that areca nut extract may impair oral fibroblasts and then modulate the progression of oral epithelial oncogenesis via their secreted molecules.

Interaction between zonal populations of articular chondrocytes suppresses chondrocyte mineralization and this process is mediated by PTHrP.

OBJECTIVE: Articular cartilage is separated from subchondral bone by the tidemark and a calcified cartilage zone. Advancement of the calcified region and tidemark duplication are both hallmarks of osteoarthritis (OA). Currently the mechanisms controlling post-natal articular cartilage mineralization are poorly understood. The objective of this study is to test the hypothesis that cellular communication between different cartilage layers regulates articular chondrocyte mineralization. DESIGN: Co-culture models were established to evaluate the interaction of chondrocytes derived from the surface, middle and deep zones of articular cartilage. The cultures were stimulated with triiodothyronine (T3) to promote chondrocyte hypertrophy. The effects of zonal chondrocyte interactions on chondrocyte mineralization were examined over time. RESULTS: Co-culture of deep zone chondrocytes (DZCs) with surface zone chondrocytes (SZCs) suppressed the T3-induced increase in alkaline phosphatase (ALP) activity and related mineralization. Moreover, SZC-DZC co-culture was associated with a significantly higher parathyroid hormone-related peptide (PTHrP) expression when compared to controls. When PTHrP(1-40) was added to the DZC-only culture, it suppressed DZC ALP activity similar to the inhibition observed in co-culture with SZC. In addition, treatment with PTHrP reversed the effect of T3 stimulation on the expression of hypertrophic markers (Indian hedgehog, ALP, matrix metalloproteinases-13, Type X collagen) in the DZC cultures. Moreover, blocking the action of PTHrP significantly increased ALP activity in SZC+DZC co-culture. CONCLUSION: Our findings demonstrate the role of zonal chondrocyte interactions in regulating cell mineralization and provide a plausible mechanism for the post-natal regulation of articular cartilage matrix organization. These findings also have significant implications in understanding the pathology of articular cartilage as well as devising strategies for functional cartilage repair.

Important prognostic factors in patients with skull base erosion from nasopharyngeal carcinoma after radiotherapy.

PURPOSE: To evaluate the long-term outcome and prognostic factors in patients with skull base erosion from nasopharyngeal carcinoma after initial radiotherapy (RT). METHODS AND MATERIALS: From January 1985 to December 1986, 100 patients (71 males, 29 females) with a diagnosis of nasopharyngeal carcinoma were found on computed tomography (CT) to have skull base erosion. The mean age was 41 years (range 16-66). Ninety-six patients had World Health Organization type III undifferentiated carcinoma, and 4 had type I. The metastatic workup, including chest radiography, liver ultrasound scanning, and liver function test was negative. All patients underwent external beam RT (EBRT) alone to 66-80 Gy during 6-8 weeks. A daily fraction size of 2 Gy was delivered using 60Co or a linear accelerator. No patient received chemotherapy. All patients were followed at regular intervals after irradiation. The median follow-up was 22.3 months (range 2-174). Survival of the cohort was computed by the Kaplan-Meier method. The potential prognostic factors of survival were examined. Multivariate analyses were performed using the Cox regression model. RESULTS: The 1, 2, 5, and 10-year overall survival rate for the cohort was 79%, 41%, 27%, and 13%, respectively. However, the subgroup of patients with both anterior cranial nerve (I-VIII) and posterior cranial nerve (IX-XII) involvement had a 5-year survival of only 7.7%. A difference in the time course of local recurrence and distant metastasis was observed. Both local recurrence and distant metastasis often occurred within the first 2 years after RT. However, local relapse continued to occur after 5 years. In contrast, no additional distant metastases were found after 5 years. The causes of death included local recurrence (n = 59), distant metastasis (n = 21), both local recurrence and distant metastasis (n = 1), and unrelated causes (n = 5). After multivariate analysis, complete recovery of cranial nerve involvement, cranial nerve palsy, and headache after irradiation were found to be independent prognostic factors in this cohort. CONCLUSIONS: We present one of the longest follow-ups of patients with nasopharyngeal carcinoma invading the skull base. Our results demonstrate the importance of cranial nerve involvement, recovery of headache, and cranial nerve palsy. These factors should be carefully evaluated from the history, physical examination, and imaging studies. A subgroup of patients with skull base involvement had long-term survival after RT alone. The findings of this study are important as a yardstick against which more aggressive strategies, such as combined radiochemotherapy and altered fractionation RT can be compared.

Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--a preliminary report.

PURPOSE: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. METHODS AND MATERIALS: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score >or=7, pretreatment PSA >or=10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. RESULTS: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients (27%) with Grade 1, and 9 patients (30%) with no toxicity. No patient dropped out from the trial or had to withhold treatment because of severe toxicity. CONCLUSIONS: This is the first trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of radiotherapy by combining in situ gene therapy. Initial experience has demonstrated the safety of this approach. There is no added toxicity to each therapy used alone. Long-term follow-up and larger cohort studies are warranted to evaluate long-term toxicity and efficacy.