Hideo Fukano

Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma

Many histopathologic parameters in head and neck squamous cell carcinoma have been identified as predictive factors for cervical metastasis. Several studies focused on tumor thickness, and the depth of invasion was suggested to have a relationship to the occurrence of cervical metastasis. Nonetheless, the criterium for elective neck therapy in terms of tumor depth is still inconclusive. Therefore, a retrospective study was undertaken to substantiate the differing results in the literature with our own findings concerning the interrelationship between tumor thickness and clinically suspicious neck, as well as occult neck disease. In addition, the study attempted to identify further predictive factors for cervical metastasis in squamous cell carcinoma of the tongue.

Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese

A population-based case-control study was designed for the investigation of any association between serum micronutrient levels and oral leukoplakia. Out of a total of 9536 subjects over the age of 40 years who participated in the oral mucosal screening programme in Tokoname city, 48 cases detected with oral leukoplakia (38 male:10 female) were recruited. For each case, four controls matched by age and sex were selected from the same cohort. We examined the fasting serum levels of retinol, alpha-tocopherol, zeaxanthin and lutein, cryptoxanthin, lycopene and carotenoids (alpha-carotene and beta-carotene) by high-performance liquid chromatography. Among males with leukoplakia mean serum lycopene and beta-carotene levels (0.175+/-0.202, 0.357+/-0.295 micromol/l) were significantly lower than those of controls (0.257+/-0.252, 0.555+/-0.408 micromol/l) (P<0.05, P<0.005). Logistic regression analysis with leukoplakia as the dependent variable showed that high serum levels of beta-carotene were related to low risk of oral leukoplakia (odds ratio 0.160, 95% C.I.: 0.029-0.866, P<0.05). There were no significant differences in any of the serum nutrients estimated in female subjects. Our results suggest for the first time that high serum levels of beta-carotene may provide protection against oral precancer for the Japanese male.

Outcome following a population screening programme for oral cancer and precancer in Japan

The purpose of this study was to evaluate the validity and outcome of an oral mucosal screening programme conducted in Japan. All adults over the age of 40 years resident in Tokoname city were invited by letter to attend a free general health screen and oral examinations annually. Twenty- to 39-year-old females were also encouraged to participate. During the years 1996-98, a total of 19056 subjects (5885 male, 13171 female: mean age 60.7+/-11.3 years) were examined by three types of screeners: postgraduate dental residents (n=17), hospital dentists (n=5) and general dental practitioners (n=15). In the cohorts examined screening dentists recorded oral mucosal lesions in 783 (4.1%) subjects. Of those detected with mucosal lesions, 200 (25.5%) were referred and 137 (68. 5%) attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Thirty-nine subjects were confirmed as having oral cancer or precancer (two squamous cell carcinomas, 37 leukoplakias) and 40 with lichen planus. Five false positives (3.6%) were found. Among the cases referred under other diagnostic labels no cancers were detected. Among those who attended for confirmation of oral cancer or precancer by a specialist, sensitivity, specificity and positive predictive value were 0.92, 0.64 and 0.78, respectively. In males with oral cancer/leukoplakia, the prevalence of smoking, drinking and combined habits was higher than those with lichen planus or among negative subjects. The sensitivity and specificity determined from this research suggests that the performance of the Japanese dentists employed in screening was satisfactory. An attendance of 68% for re-examination by specialists compares well with other reported studies measuring patient compliance.

Oral cancer screening as an integral part of general health screening in Tokoname City, Japan.

Objectives To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. Methods In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. Results A total of 19 305 subjects (5955 males, 13 350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. Conclusions The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74–76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit.

Diagnosis of oral mucous membrane pemphigoid by means of combined serologic testing

OBJECTIVE Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease caused by various autoantibodies. This study aimed to evaluate the diagnostic value of MMP-specific autoantibodies in patient sera. STUDY DESIGN We analyzed sera from 30 MMP-suspected patients with intractable oral mucosal lesions using a combination of indirect immunofluorescence with 1M NaCl-split skin, immunoblot analysis, and ELISAs. We also analyzed clinical features among different types of MMP. RESULTS Seventeen, 4, and 3 patients were diagnosed with anti-BP180-type MMP, anti-laminin-332-type MMP, and combined anti-BP180/anti-laminin-332-type MMP, respectively. CONCLUSIONS Our results indicated that a combination of immunologic testing for circulating autoantibodies is useful for the diagnosis of MMP.

Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: A randomized controlled trial

Management of oral leukoplakia—a potentially malignant disorder—is currently not evidence‐based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi‐centre, randomized, double‐blind controlled trial (RCT) was undertaken to evaluate the use of low‐dose beta‐carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day−1 of beta‐carotene and 500 mg day−1 of vitamin C) or placebo arm (50 mg day−1 of vitamin C). Current or ex‐smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1‐year and the likelihood of malignant transformation during a 5‐year follow‐up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60‐month follow‐up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention‐to‐treat principle, relative risk by supplementing with beta‐carotene and vitamin C was 0.77 (95%CI: 0.28–1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side‐effects were noted. Beta‐carotene (10 mg day−1) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.

Risk of surgical glove perforation in oral and maxillofacial surgery.

Oral and maxillofacial surgery, which involves several sharp instruments and fixation materials, is consistently at a high risk for cross-contamination due to perforated gloves, but it is unclear how often such perforations occur. This study aimed to address this issue. The frequency of the perforation of surgical gloves (n=1436) in 150 oral and maxillofacial surgeries including orthognathic surgery (n=45) was assessed by the hydroinsufflation technique. Orthognathic surgery had the highest perforation rate in at least 1 glove in 1 operation (91.1%), followed by cleft lip and palate surgery (55.0%), excision of oral soft tumour (54.5%) and dental implantation (50.0%). The perforation rate in scrub nurses was 63.4%, followed by 44.4% in surgeons and first assistants, and 16.3% in second assistants. The odds ratio for the perforation rate in orthognathic surgery versus other surgeries was 16.0 (95% confidence interval: 5.3-48.0). The protection rate offered by double gloving in orthognathic surgery was 95.2%. These results suggest that, regardless of the surgical duration and blood loss in all fields of surgery, orthognathic surgery must be categorized in the highest risk group for glove perforation, following gynaecological and open lung surgery, due to the involvement of sharp objects.

Clinical and immunological profiles of anti-BP230-type bullous pemphigoid: Restriction of epitopes to the C-terminal domain of BP230, shown by novel ELISAs of BP230-domain specific recombinant proteins

ObjectivesTo confirm that sera from some BP patients reactive exclusively to the BP230 and to study the clinical and immunological characteristics of this condition.Materials and methodsBP patients were divided into three groups: BP reactive only to BP230 (BP230- BP), BP reactive to both BP180 and BP230 (BP180-BP230-BP) and BP reactive only to BP180 (BP180-BP), based on the results of standard ELISAs for BP180 and BP230. Clinical features were statistically analyzed among the three groups. Then, targeted epitopes in each group were studied by immunoblotting and novel ELISAs using three domainspecific BP230 recombinant proteins.ResultsForty-one, 65 and 47 of 153 BP patients were categorized as BP230-BP, BP180-BP230-BP and BP180-BP, respectively. Clinically, BP230-BP patients showed significantly lower severity, less need of systemic steroids and better responses to various treatments, suggesting that BP230-BP is a milder condition. Immunoblotting and ELISAs of domain-specific BP230 recombinant proteins indicated that, while BP180-BP230-BP sera reacted with all three domains of BP230, BP230-BP sera reacted more frequently with epitopes in the BP230 C-terminal domain.ConclusionWe propose a new disease entity, named anti-BP230-type BP, in which anti-BP230 antibodies might be pathogenic and react specifically with the BP230 C-terminal domain. While anti-BP230 antibodies in BP180-BP230-BP seem to be produced via intermolecular epitope spreading, anti-BP230 antibodies in BP230-BP are considered to be produced by different mechanisms.

Massive immature teratoma in a neonate

Teratomas are embryonal tumours composed of diverse tissues from three germinal layers with variable levels of maturity. The authors report a female patient with a large immature epignathus. Prenatal diagnosis permitted a caesarean section and tracheotomy to be planned under ex utero intrapartum treatment for airway obstruction. The tumour was successfully controlled, even though it was impossible to distinguish from normal tissue because it lacked a pedicle and capsule, using multidisciplinary therapy, including a series of surgical treatments and adjuvant chemotherapy. This case suggested that the level of serum alpha fetoprotein might be a useful indicator after surgery. At present, after 4 years, no regrowth has been observed and the patient has no problems with respiration or swallowing.

p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia

BACKGROUND We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses. METHODS For this biomarker study, we included all subjects in the experimental group (n = 23) who were non-smokers. Among 16 who completed the trial for 1 year of supplementation, there were four responders and 12 non-responders at 1-year follow-up. Following immuno-staining for p53 and ki67, the percentage of positive cell nuclei were analyzed as labeling index (LI). RESULTS Expression of p53 was greater in basal layers than in para-basal layers. Mean para-basal LI of p53 was higher in non-responding (26.0) than in responding subjects (11.2) (P = 0.028). ki67 LIs were not significantly different in the two groups. CONCLUSIONS Expression of p53 was inversely related to clinical response to the supplements. Other biomarkers that may recognize subjects responsiveness to chemoprevention require further study.