Management of oral leukoplakia by laser surgery: relation between recurrence and malignant transformation and clinicopathological features

OBJECTIVE: The aim of the present study was to assess the clinical usefulness of laser surgery for oral leukoplakia. BACKGROUND: Recurrence and/or malignanT transformation of oral leukoplakia have occasionally been observed following laser surgery. It is reported that the rate of recurrence was 7.7-38.1%, while malignant transformation was 2.6-9%. MATERIALS AND METHODS: A total of 154 oral leukoplakias from 116 patients were treated in our department. Comparisons with the rate of recurrence, malignant transformation and clinical futures, epithelial dysplasia, location, and treatment procedure were examined. To evaluate recurrence and malignant transformation, the cases were restricted to those with a minimum follow-up of 6 months. RESULTS: A total of 97 lesions fulfilled this criterion. The rate of recurrence had no association with the location or the epithelial dysplasia, although it differed with the treatment procedure. The rate of recurrence in laser surgery was approximately 29%. Malignant transformation was observed in four of 97 lesions. They were observed in 13.6% of tongue cases and 1.8% of gingival cases. Three of four lesions were treated with excision surgery, and the remaining one treated with laser vaporization. Only 1.2% malignant transformation in laser surgery was revealed. CONCLUSION: Laser excision is suitable for leukoplakia cases on non-keratinized epithelia (i.e., the tongue and buccal mucosa), while laser vaporization is suitable for the gingival cases. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction. We believe that laser surgery is an excellent procedure.     

Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats

Hepatocyte growth factor (HGF), an organotropic factor for regeneration and protection in various organs, has the ability to attenuate cerebral ischemia-induced cell death. The effect of HGF on learning and memory function after cerebral ischemia, however, remains unknown. We have demonstrated that administration of human recombinant HGF (hrHGF) into the ventricle reduced prolongation of the escape latency in acquisition and retention tests of the water maze task on Days 12-28 after microsphere embolism-induced cerebral ischemia. Treatment with hrHGF also attenuated the decrease in viable area and the density and number of perfused cerebral vessels, particularly those with a diameter smaller than 10 microm, of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We observed that treatment with hrHGF reduced the number of TUNEL-positive cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF prevents learning and memory dysfunction seen after sustained cerebral ischemia by protecting against injury to the endothelial cells. HGF treatment may be a potent therapeutic strategy for cerebrovascular diseases, including cerebral infarct and vascular dementia.     

Gene therapy with secretory leukoprotease inhibitor promoter-controlled replication-competent adenovirus for non-small cell lung cancer

Secretory leukoprotease inhibitor (SLPI) is highly expressed in almost all non-small cell lung cancers (NSCLCs), but not in the majority of other tumor types. In an attempt to create a specific gene therapy for NSCLC, we constructed AdSLPI.E1AdB, an adenovirus vector with a double expression cassette consisting of E1A driven by the SLPI promoter gene followed by E1B-19K under the control of the cytomegalovirus (CMV) promoter that can selectively replicate only in NSCLC cells. Infection with AdSLPI.E1AdB yielded E1A protein expression and adenovirus replication resulting in a >100-fold increase of the virus titers only in SLPI-producing NSCLC cells (A549, H358, and HS24 cells). In contrast, neither E1A protein nor replication was detected in non-SLPI-producing HepG2 cells. Treatment with AdSLPI.E1AdB significantly inhibited the proliferation of NSCLC cells in vitro in a dose-dependent manner, whereas the cell growth of HepG2 or normal human bronchial epithelial cells was not affected by AdSLPI.E1AdB infection. Direct injection of AdSLPI.E1AdB into A549 and H358 tumors in nude mice resulted in a marked reduction in tumor growth compared with controls (A549, 57%, P < 0.02; H358, 67%, P < 0.03). Histological examination revealed the replication of AdSLPI.E1AdB and strong induction of necrosis and apoptosis. In addition, we evaluated the combination of AdSLPI.E1AdB and AdCMV.NK4 encoding NK4 protein, which has strong antiangiogenic activity. E1A expressed by AdSLPI.E1AdB trans-acts on the replication of AdCMV.NK4 and thus increases the expression of NK4. Injection of these two vectors into H358 tumors resulted in a more striking reduction of tumor growth compared with single injection of each vector. These results suggest that AdSLPI.E1AdB could provide a selective therapeutic modality for NSCLC and that the combination of AdSLPI.E1AdB and AdCMV.NK4 may be a more effective gene therapy for NSCLC.     

A new screening method to diagnose coronary artery disease using multichannel magnetocardiogram and simple exercise

Background: Magnetocardiography (MCG) is a non-contact mapping technique to record cardiac action currents. The Master's two-step electrocardiogram (ECG) test is a simple exercise method for screening coronary artery disease (CAD), but it is inadequate concerning the sensitivity. Our aim was to develop a new screening method using multichannel MCG instead of ECG. Methods: Thirty subjects (aged 54 ± 16 years, 27 males), 17 of whom had CAD confirmed by coronary angiography, underwent the Master's exercise ECG test. After the exercise, MCG signals were acquired every minute during recovery with a 64-channel MCG system (MC-6400, Hitachi Ltd). We integrated tangential components of the MCG signals within QRS (during 20, 40, 80, and 120 ms centering on R-wave peak) immediately after exercise (Iex) and 5 minutes after exercise (Irec). The exercise-induced change of currents [(Iex-Irec)/Irec] was determined and normalized for each channel, and the maximal change among 64 channels, maximal QRS integral change, was used as a diagnostic index for myocardial ischemia. Results: The maximal QRS integral change during 40 ms was significantly higher in the CAD group than in the control group (0.81 ± 0.51 vs. 0.36 ± 0.19, p < 0.01). A sensitivity and specificity for predicting CAD by the change > 0.44 were 82 % and 85 %, respectively, yielding a diagnostic accuracy of 83 %. The conventional Master's ECG test identified the CAD patients with a diagnostic accuracy of 63 % (sensitivity 47 %, specificity 85 %). Conclusion: The Master's two-step exercise test with a 64-channel MCG system showed the high diagnostic accuracy, despite of non-contact recording and simple exercise. The magnetic field in the depolarization process has the potential to detect the subtle myocardial ischemia induced by exercise. Received: 20 June 2002, Returned for 1. revision: 11 July 2002, 1. Revision received: 3 September 2002, Returned for 2. revision: 25 September 2002, 2. Revision received: 10 October 2002, Accepted: 14 October 2002 Correspondence to: S. Nakatani, MD, PhD     

Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells

We have shown previously that KIAA0223, a gene encoding a minor histocompatibility antigen, HA-1, whose expression was believed to be restricted to the hematopoietic cells, is aberrantly expressed in some solid tumor cell lines. However, its significance in tumor immunity needs to be determined. Cytotoxic activity of HA-1(H)-specific cytotoxic T lymphocytes (CTLs) was assessed against solid tumor cell lines expressing KIAA0223 using (51)Cr release assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately expressed. One of the two CTL-resistant cell lines became susceptible after treatment with IFN-gamma and TNF-alpha, while the other was lysed only after pulsing with HA-1(H) peptide. In most cell lines tested, HA-1(H) peptide was properly generated and presented for recognition by the CTL. However, impaired antigen processing and presentation observed in this study may result in escape from CTL recognition in vivo, as well as in vitro, as observed in this study.     

Review of 26 patients operated on for primary hyperparathyroidism

The traditional surgical approach for primary hyperparathyroidism (PHP) is routine bilateral neck exploration. At Saiseikai Utsunomiya Hospital, however, unilateral exploration, and the direct resection of one gland is performed if single gland enlargement is suspected, based on the findings of several preoperative localization procedures. Here, we reviewed 26 patients who underwent single gland operations for PHP at our institution between 1993 and 2001. The 26 patients (21 women and 5 men) ranged in age from 20 to 79 years (mean, 54.8 years). None of the patients had multiple endocrine neoplasia (MEN), familial hypercalcemia, or malignant tumors. At least three preoperative localization procedures, such as ultrasonography, computed tomography, thallium technetium scanning, 99mTc sestamibi scintigraphy, or magnetic resonance imaging, were performed in each patient. A parathyroidectomy was then performed under general anesthesia. Contralateral exploration was not routinely performed. In addition, an intraoperative biopsy of the other glands was not performed. The following data were retrospectively collected in all patients: serum calcium, and the HS-PTH at one month and 6 months after the parathyroidectomy. All patients were normocalcemic, and the serum HS-PTH concentration significantly decreased in all patients after this operation. Patients were divided into two groups (adenoma group, n = 16; hyperplasia group, n = 6) and the data was analyzed according to the histological and pathological diagnosis. In both pathological groups, all patients were normocalcemic and the serum HS-PTH concentration was significantly lower after surgery. The serum HS-PTH concentration showed no significant difference between the adenoma group and the hyperplasia group at 6 months after surgery. No complications, including recurrent laryngeal nerve palsy or permanent hypocalcemia, were observed after surgery. In conclusion, if a single gland disease is suspected based on the findings of multiple preoperative localization procedures, resection of the enlarged gland alone appears to provide good results for the treatment of either adenoma or hyperplasia resulting in PHP. In addition, this procedure also reduces the occurrence of postoperative hypocalcemia, because the normal glands are not injured by the biopsy procedures.     

Nocturnal pulse oximetry diagnosis for screening pediatric obstructive sleep apnea syndrome

We evaluated the diagnostic value of pulse oximetry during sleep in pediatric obstructive sleep apnea syndrome (OSAS) caused by adenoid-tonsil hypertrophy. Subjects were 22 healthy children free of symptoms such as snoring, sleep apnea and oral breathing and 163 children suspected of OSAS with snoring or sleep apnea. Subjects were measured for percutaneous oxygen saturation (SpO2) during sleep. Of those with suspected OSAS, 69 underwent adenotonsillectomy and were measured for SpO2, both pre- and postoperatively, then pre- and postoperative measurements were compared. After measurement, we analyzed three parameters: lowest saturation (LSpO2), the desaturation index, and total desaturation duration under 95% (TDD95). Few abnormal findings were seen in healthy children. We calculated the mean and standard deviation (SD) of each parameter and set borderlines of mean-2SD for LSpO2 and mean + 2SD for ODI and TDD95. With these borderlines, 105 children for LSpO2, 75 for ODI and 76 for TDD 95 were judged to be normal among the 163 with suspected OSAS. Histograms showed that the mode of each parameter was situated near the borderline. Comparison between pre- and postoperative measurements showed that the effect of the surgery strongly correlated with preoperative measurement in patients undergoing surgery. Assuming that a patient with postoperative improvement is positive, we calculated sensitivity and specificity for each borderline measurement. We found that if success is 100%, the borderline should be 87% for LSpO2, 3.5 for ODI, and 30.0 for TDD95. If success exceeds 90%, the borderline should be 90% for LSpO2, 2.0 for ODI, and 7.0 for TDD95. We therefore conclude that measurement of SpO2 during sleep is useful in screening for pediatric OSAS.