Satoshi Yokoo

Premalignant melanocytic dysplasia and malignant melanoma of the oral mucosa

Although malignant melanoma of the oral cavity frequently arises in pre-existing melanosis of the oral mucosa, little is known about oral melanoma precursor lesions. We reviewed three patients with premalignant melanocytic dysplasia and 14 with malignant melanoma of the oral mucosa. Thirteen of the 14 malignant melanoma cases had radial growth phases similar to those of acral lentiginous melanoma (ALM) of the skin. The prognosis of oral melanoma was not poor in contrast to that of cutaneous melanoma. Premalignant melanocytic dysplasia of the oral mucosa showed lentiginous or pagetoid proliferation of atypical melanocytes in the lower epithelium in the central part of the lesion, and lentiginous proliferation of dendritic melanocytes or simple hyperpigmentation in the basal cell layer in the peripheral part. These findings were similar to those of the radial growth phase of ALM of the oral mucosa.

Do multiple venous anastomoses reduce risk of thrombosis in free-flap transfer? Efficacy of dual anastomoses of separate venous systems.

Whether or not multiple venous anastomoses reduce the risk of free-flap failure is a subject of controversy. We report here, for the first time, on the importance of selecting 2 separate venous systems of the flap for dual anastomoses. The efficacy of multiple anastomoses was verified through a retrospective review of 310 cases of the free radial forearm flap transfer. Dual anastomoses of separate venous systems (the superficial and the deep) showed a lower incidence of venous insufficiency than single anastomosis did (0.7% versus 7.5%; P < 0.05). On the other hand, dual anastomoses of a sole venous system showed no significant difference in the incidence of venous insufficiency compared with single anastomosis (11.5% versus 7.5%; P = 0.48). Our results suggest that dual venous anastomoses of separate venous systems is conducive to reduced risk of flap failure and affords protection against venous catastrophe through a self-compensating mechanism that obviates thrombosis of either anastomosis.

Tumor-doubling time and onset of pulmonary metastasis from adenoid cystic carcinoma of the salivary gland

Adenoid cystic carcinoma (ACC), an uncommon malignancy in the head and neck region, invades diffusely and often metastasizes to the lung, although the growth rate is very slow. A retrospective study was conducted in 30 patients with ACC to ascertain the frequency of pulmonary metastasis, the doubling time of metastatic tumor deposits, and the time of onset for pulmonary metastasis. The following results were obtained: (1) Of 30 patients with ACC, 21 had pulmonary metastases (4 initially and 17 during observation), 7 were free of metastases but have not been observed for 5 years, and 2 were free of metastases for more than 5 years but less than 10 years after the initial treatment. The cumulative metastasis rate at 5 and 10 years for this group of patients was 70% and 100%, respectively. (2) Patients with T1 or T2 tumors that have a tubular or cribriform histopathologic pattern showed pulmonary metastases about 20 months later than those with T3 or T4 tumors and a solid pattern. However, the final metastasis rate did not differ between the 2 groups after a long period. (3) The tumor doubling time of the metastatic deposits of ACC was 86 to 1064 days with an average of 393 days, which was much longer than that of most other malignant neoplasms reported previously. (4) The time of onset of pulmonary metastasis was calculated to be much earlier (average of 227 months) before the first visit. These findings suggest that the treatment method for ACC should be chosen with the consideration that many of the patients may have occult pulmonary metastases at the time of their initial evaluation.

Ror2 expression in squamous cell carcinoma and epithelial dysplasia of the oral cavity

In this study, the expressions of Ror2 in the normal mucosa, the epithelium dysplasia, and squamous cell carcinoma (SCC) of the oral cavity were investigated, and possible differences in the expression patterns of Ror2 and of p53, Ki67, or PCNA were examined. In Western blotting analyses, Ror2 expression in oral cancer was significantly higher than that in the normal oral mucosa. Immunohistochemically, Ror2 was localized on the plasmalemma and in the rough endoplasmic reticulum (rER). The tissue area with an Ror2-positive expression tended to differ from the area with a positive expression of p53, ki67, or PCNA, and the number of cells with an Ror2 expression tended to increase as the degree of malignancy rose in the epithelial tissues. These results suggest that Ror2 was not related to cell proliferation, but rather associated with cell polarity and cell motility, and that it was also closely associated with the degree of malignancy in oral epithelial tissue.

Function of the Membrane Water Channel Aquaporin-5 in the Salivary Gland

The process of saliva production in the salivary glands requires transepithelial water transfer from the interstitium to the acinar lumen. There are two transepithelial pathways: the transcellular and paracellular. In the transcellular pathway, the aquaporin water channels induce passive water diffusion across the membrane lipid bilayer. It is well known that aquaporin-5 (AQP5) is expressed in the salivary glands, in which it is mainly localized at the apical membrane of the acinar cells. This suggests the physiological importance of AQP5 in transcellular water transfer. Reduced saliva secretion under pilocarpine stimulation in AQP5-null mice compared with normal mice further indicates the importance of AQP5 in this process, at least in stimulated saliva secretion. Questions remain therefore regarding the role and importance of AQP5 in basal saliva secretion. It has been speculated that there would be some short-term regulation of AQP5 such as a trafficking mechanism to regulate saliva secretion. However, no histochemical evidence of AQP5-trafficking has been found, although some of biochemical analyses suggested that it may occur. There are no reports of human disease caused by AQP5 mutations, but some studies have revealed an abnormal subcellular distribution of AQP5 in patients or animals with xerostomia caused by Sjögren’s syndrome and X-irradiation. These findings suggest the possible pathophysiological importance of AQP5 in the salivary glands.

Simple reconstruction with titanium mesh and radial forearm flap after globe-sparing total maxillectomy: a 5-year follow-up study.

Background: Reconstruction of eye globe–sparing total maxillectomy defects is one of the major challenges to reconstructive surgeons. In 1994, the authors developed an uncomplicated and easy reconstructive method, where a titanium mesh is applied for the support of orbital contents, a radial forearm free flap for covering the mesh and the cheek lining, and an obturator prosthesis for palatal and dental rehabilitation. Methods: Five patients who underwent primary reconstruction with the authors’ method after globe-sparing maxillectomy with loss of the orbital floor from 1994 to 1999 and who were followed up for more than 5 years were retrospectively reviewed for (1) the presence of diplopia, (2) the shape of the reconstructed orbital floor assessed by coronal section magnetic resonance imaging, and (3) the presence of infection/exposure of the titanium mesh. Results: Only one of the five patients developed slight diplopia. Coronal magnetic resonance imaging showed that the orbital floor restored with titanium mesh had in all cases maintained a proper shape and position for more than 5 years. No infection or exposure of the titanium mesh had developed in any of the cases, despite exposure to irradiation of not less than 30 Gy. All the patients had well-retentive obturator prostheses. Conclusion: This long-term follow-up study demonstrated that the authors’ method attained a long-lasting successful outcome functionally and is the method of choice for reconstruction after globe-sparing total maxillectomy.

Constitutional mutation of keratin 13 gene in familial white sponge nevus

OBJECTIVE We sought to investigate a novel mutation in the keratin genes assumed to be responsible for a familial case of oral white sponge nevus. PATIENTS AND METHODS The affected family consisted of a 36-year-old woman, her 17-year-old daughter, and her 14-year-old son. Keratin 4 and 13 genes extracted from venous blood lymphocytes were amplified by using the polymerase chain reaction and directly sequenced. RESULTS Sequencing analysis of the 3 patients revealed the presence of a novel heterozygous T-to-C transition mutation in exon 1 of the keratin 13 gene, with no abnormalities detected in the keratin 4 gene. CONCLUSION We identified a novel heterozygous missense mutation at 332T>C in the keratin 13 gene believed to be related to the development of white sponge nevus.

Treatment and prognosis of malignant melanoma of the oral cavity: preoperative surgical procedure increases risk of distant metastasis

OBJECTIVE Many authors have reported that oral melanoma patients showed much worse prognosis than those with cutaneous melanoma. We investigated treatment method and prognosis of patients with oral malignant melanoma. STUDY DESIGN Twenty-one patients with oral melanoma treated at our hospital were investigated, with special reference to the influence of preoperative surgical procedures such as biopsy, incision, or tooth extraction on the prognosis. RESULTS All patients underwent surgery followed by immuno-chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), ninustine hydrochloride (ACNU), vincristine (VCR), and biologic response modifier OK-432. Local control was obtained in 20 of 21 patients. Lymph node metastasis appeared in 13 patients, but neck failure was not detected in any patients. Distant metastasis occurred in 9 patients in spite of loco-regional control. Five-year survival rate of 12 patients with no preoperative surgical procedure was 91.7%, while that of the 9 patients who had undergone surgical procedures before treatment was 25.9% (P < .05). CONCLUSIONS Oral melanoma patients can obtain a prognosis as good as that for cutaneous melanoma patients, when the above-mentioned therapy is used without any preoperative surgical procedures.

Evaluation of T-classifications of upper gingival and hard palate carcinomas—a proposition for new criterion of T4

Most carcinomas of upper gingiva and hard palate are classified as T4 stage on the basis of the UICC criteria, since they easily invade the underlying bone tissue. We classified 43 patients with squamous cell carcinoma of the upper gingiva in terms of three criteria: (1) the original T-classification by UICC, (2) the classification by the Japan Society for Head and Neck Cancer (JSHNC), and (3) a new classification in which the maxillary sinus or nasal floor is used as the defining borderline for T4 (MSF classification). Our study demonstrated that the new classification was superior with regard to distribution of patients by T stage, correlation with prognosis and choice of treatment method.

Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth

In squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM), it is important to predict lymph node metastasis, including occult metastasis, before operating. The purpose of this study was for us to determine practical histopathologic parameters as predictive factors for lymph node metastasis in preoperative SCC biopsy specimens.