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CYP2D6 poor metaboliser genotype and oral squamous cell carcinoma
268
British
Trigeminal .I P. M.
Journal
nerve Vriens,
of Oral
morbidity M. L. M
and Maxillofacial following J. Lurik*
Surgery
mandibular implant surgery. & M. V. Uil*. Department
Oral & Maxillofacial Surgery and Special Dental Care, Utrecht University, Utrecht, the Netherlands; Department Oral & Maxillofacial Surgery, Slingeland Hospital, Doetinchem, The Netherlands*. Implant surgery involves mucoperiosteal flap elevation, bone removal and implant placement, all of which could endanger the mental nerve. This prospective study was designed to assessthe function of the trigeminal nerve following mandibular implant surgery by means of psychophysical testing. We evaluated 38 patients (median age of 61 years; 10 males and 28 females) following the placement of implants (Branemark System, Nobelpharma) in the lower jaw anterior to the mental foramen. A total of 118 implants were inserted. The neurosensory evaluation included two-point discrimination (2pntD; MacKinnonDellon Disk-Criminator) and light touch sensation (LTS; SemmesWeinstein Monofilaments). Trigeminal nerve function was examined preoperatively and until 6 months after surgery. Data were analysed statistically using a t test (paired samples) and ANOVA (two-factor with replication). Abnormal sensation in the distribution of the mental nerve was reported by 22 patients in 34.2% of the sides tested 3 months after surgery. At 6 months’ time following surgery 12 patients reported altered sensation in 13.2% of the sides tested. By 3 and 6 months the test values for moving 2pntD and LTS were statistically significant different when compared with preoperative values. Patients with 4 implants were significantly more likely to develop abnormal function of the trigeminal nerve than patients with 2 implants. The factors gender and age showed no significant difference in the outcome of the different psychophysical tests. The discrepancy in outcome between subjective reports on asking and psychophysical tests was as to be expected but could also suggest a high satisfaction with the implant surgery performed. This study has shown that the prevalence of altered sensation following mandibular implant surgery may be higher than previously thought. Further prospective studies are required to more accurately document the complication of altered sensation following mandibular implant surgery. Does intraoperative nerve encounter and other parameters influence the inferior alveolar nerve function after sagittal split ramus osteotomy of the mandible? Anders Westermark, Hans Bystedt & Lars von Konow. Department of Maxillofacial Surgery, Karolinska
Hospital, Stockholm, Sweden. Direct trauma to the Inferior Alveolar Nerve (IAN) during Sagittal Split Ramus Osteotomy (SRO) of the mandible has been claimed to be responsible for postoperative neurosensory dysfunction of the lower lip and chin area. The relatively high frequency of such neurosensory dysfunction described in the literature makes it a disquieting drawback of the surgical procedure. Tearing of the nerve due to mandibular advancement and nerve compression due to various types of osteosynthesis also have been suggested to cause reduced IAN function after SRO. Influence of patient’s age and sex also has been mentioned. In an analysis of IAN function of 496 mandibular sides operated on with SRO the nerve function 2 years after surgery was correlated to a series of parameters including patient’s age and sex, degree of intraoperative nerve encounter/damage, degree of mandibular advancement, type of osteosyhthesis and experience of the surgeon. The sensibility of the lower-lip and chin area was determined by light touch perception and was divided into fully normal sensibility, almost normal and reduced sensibility. Of the operated sides 59.7% demonstrated fully normal sensibility; 20.8% almost normal and 19.5% reduced sensibility. The patient’s age was significantly correlated to the degree of neurosensory dysfunction and the surgeon’s experience also seemed to influence the neurosensory function after SRO. However, the degree of intraoperative nerve encounter/damage did not correlate to the degree of IAN dysfunction nor did parameters such as degree of mandibular advancement and type of osteosynthesis. Based on our findings which will be presented in detail we suggest that the soft tissue dissection on the medial aspect of the mandibu-
lar ramus might be co-responsible for the neurosensory dysfunction observed after SRO. The possible derangements:
role of the mandibular condyle in painful MRI findings. J. Widelec & J. Van Reck*.
internal
MRI and CT Unit Department of Medical Imaging, lnstitut Bordet, Brussels; *Department of Maxillo-facial Surgery, Hopital Universitaire Saint-Pierre Brussels.
Two-hundred MRI studies (400 TMJ) were analysed. Each patient underwent a standard MRI study including both joints with sagittal and coronal views. Whenever no explanation for the pain was found an additional sequence (T2 or T2*) were used to look within the bone marrow of the mandibular condyle. Twenty non symptomatic volunteers were also studied in the conditions. One patient was studied 6 months after orthognathic surgery (Dal Pont procedure). One patient had a follow-up study after splint therapy. This patient was no longer symptomatic. Joint effusion, internal derangement of the TMJ and pain are strongly linked. That is the reason why those patients were excluded. A pattern of bone marrow edema (BME) of the mandibular was observed in 20 patients. The condyle appears with a low signal intensity on the spin-echo Tl weighted images (SETlWl) and with a very high intensity on the T2 weighted images. BME is often associated with severe degeneration of the disk or disk displacements without reduction. In one patient BME was associated with a presumed chondromatosis synovialis and in another one with an osteochondritis dissecans of the condyle. Such pattern was also observed in other joints like the hip. Similarities with the hip are also observed: same evolution of the signal intensity, the reversibility of this signal abnormality under adequate treatment. The result of the follow-up study demonstrates a total recovery of the normal signal of the condyle. Repetitive microtrauma and change of the load of the condyle after orthognathic surgery are probably the cause of the signal abnormalities. In conclusion, several observations support the hypothesis that the condyle can play a role in the onset of the pain in internal derangements, However the problem of the pain is multifactorial and this study probably gives a part of the answer. CYPZD6 poor metaboliser genotype and oral squamous noma. Stephen F. Worrall. University of Keele
cell carci-
School Postgraduate Medicine North Staffordshire Hospital, UK.
of
The CYP2D6 gene is a member of the Cytochrome P450 multigene superfamily which like other P450 genes codes for the production of mono-oxygenase enzymes involved in the phase I activation of many substrates including putative oral carcinogens. CYP2D6, located on the long arm of chromosome 22 is polymorphic as a result of frameshift mutations to introns or intron/exon boundaries. Such polymorphisms are expressed phenotypically as either extensive metabolisers (EM, homozygous or heterozygous wild type), or poor metabolisers (PM, deletion of both functional alleles). The population frequency of the PM genotype amongst Caucasians is low, between 5 and 7%. Because of its central role in putative oral carcinogen activation and the potential for individual carcinogenesis susceptibility variation resulting from polymorphism. CYP2D6 polymorphism was studied in a population of patients with established oral carcinoma. Blood samples were taken from patients presenting to the Joint Oncology Clinic at the North Staffordshire Hospital and the DNA extracted using a standard Phenol/ Chloroform technique. CYP2D6 specific primers were used in a standard PCR technique followed by restriction enzyme digestion to isolate the CYP2D61 and CYP2D62 alleles. The resulting PCR/ digest product was then separated into its component parts by agarose gel electrophoresis. Compared to the population norm of 5-7%, the patient DNA had a PM rate of 25%. A highly significant increase. Because all patients were already entered onto the departmental computer oral cancer database it was possible to obtain their clinical history including stage, smoking and alcohol intake. Surprisingly, in one particular sample run, all patients found to be PM also had extensive oral mucosal dysplasia with multifocal malignant change! These results, if confirmed by future ongoing work are of great interest as they throw into doubt the currently held belief that the P450
Abstracts enzymes are necessary for toxin/carcinogen activation. Hopefully, by the September 1996 meeting I will be in a position to present CYP2D6 data from over 100 archival oral squamous cell carcinoma tissue blocks as well as more peripheral blood samples. I will either confirm or refute the current data on CYP2D6 PM genotype status and oral cancer susceptibility.
Lower third molar surgery morbidity - do senior house officers improve with experience in their resident year? A. Zachariah, T K. Ong & A. Fordvce. Maxillofacial Unit, Newcastle General Hospital, Newcastle Upon Tyne, UK. Senior house officers (SHOs) in oral and maxillofacial surgery remove lower third molars throughout their resident year. It has been shown that the morbidity rate of this common procedure is influenced by the surgeon’s experience (Journal of Oral und MaxiNofacid Surgery 1986; 44: 8.55). Therefore, the morbidity rate should improve as the SHOs become more experienced. We studied the morbidity rate of all lower third molar surgery (under local anesthesia + /- sedation and general anesthesia) carried out by 5 SHOs in the first and last quarter of their resident year. There were a total of 591 patients (1110 lower third molars). There was no permanent nerve dysaesthesia. The Table below summarises the morbidity rates. Table 1st quarter (No. of patients) Transient Lingual Inferior nerve Infection
Dysaesthesia nerve 81302 (2.6%) alveolar 61302 ( 1.9’:/;1) 68:302
(22.5%)
2nd quarter (No. of patients)
1 I,‘289 (3.8%) 4/289 ( I .3’%) JJ./289
In conclusion, there was no significant between the two periods studied.
(26.6%)
difference
Total (No. of patients)
191591 (3.2%) IO.!591 ( 1.6%) 1451591 in morbidity
(24.5%) rates
Traumatic optic nerve injury - an animal model and its implications for clinical research. M. Zerfotvski, N.-C. Gellrich, M.-M. Gellrich, E. Machtens & U. T. Easel. Department of Oral and Maxillofacial Surgery and Department of Neurophysiology of the RuhrUniversity Bochum, Germany. Apart from the complete severance of the optic nerve, the pathogenesis of blindness due to skull base fractures is poorly understood. Likewise therapeutic options remain to be elucidated.
269
We developed an animal model of traumatic optic nerve injury that is easy to handle, reproducible and quantifiable. This is a prerequisite for studies on the pathogenesis and therapy of visual impairment due to skull base trauma. Rat optic nerves were microsurgically exposed and traumatized by a special compression device (5 to 20 cN/mm’ for 1 to 30 min) (n= 150). In a second model an inflatable microballoon catheter was inserted behind the ocular bulb. saline instilled (0.220.5 ml). and left in place for 60 or 90 min. imitating retrobulbar hematoma. Rats were sacrificed after 30 days. Retinae were whole-mounted and optic nerves cross-sectioned for histologic and morphometric work-up. Optic nerve compression resulted in a loss of retinal ganglion cells and in changes of cell size. Optic nerves showed a corresponding reduction of axons, There was approx. an inverse linear relationship of retinal ganglion cell numbers and time or pressure. The second (balloon) model gave considerably less predictable results.
Soft palate reconstruction using a superiorly based pharyngeal flap. A. Zuy&m & J. S. Brown. Regional Maxillofacial Unit, Walton Hospital. Liverpool, UK. Speech and swallowing problems due to velopharyngeal incompetence may follow soft palate resection and reconstruction. Over the past 3 years we have developed the use of a superiorly based pharyngeal flap in conjunction with a radial forearm flap for soft palate reconstruction. We present our early results from a longitudinal comparative study involving 17 consecutive patients with malignant disease of the oral cavity in which a partial or total soft palate resection was required. Speech and swallowing function were assessed by patient questionnaire and videoflouroscopy using our rating scale of velopharyngeal function. The combination of the superiorly based pharyngeal and radial forearm flap results in improved speech and swallowing following three quarter and total soft palate resection. Our early results suggest that the introduction of functional tissue to the nonfunctioning flap results in a clinical improvement for the patient.
British
Trigeminal .I P. M.
Journal
nerve Vriens,
of Oral
morbidity M. L. M
and Maxillofacial following J. Lurik*
Surgery
mandibular implant surgery. & M. V. Uil*. Department
Oral & Maxillofacial Surgery and Special Dental Care, Utrecht University, Utrecht, the Netherlands; Department Oral & Maxillofacial Surgery, Slingeland Hospital, Doetinchem, The Netherlands*. Implant surgery involves mucoperiosteal flap elevation, bone removal and implant placement, all of which could endanger the mental nerve. This prospective study was designed to assessthe function of the trigeminal nerve following mandibular implant surgery by means of psychophysical testing. We evaluated 38 patients (median age of 61 years; 10 males and 28 females) following the placement of implants (Branemark System, Nobelpharma) in the lower jaw anterior to the mental foramen. A total of 118 implants were inserted. The neurosensory evaluation included two-point discrimination (2pntD; MacKinnonDellon Disk-Criminator) and light touch sensation (LTS; SemmesWeinstein Monofilaments). Trigeminal nerve function was examined preoperatively and until 6 months after surgery. Data were analysed statistically using a t test (paired samples) and ANOVA (two-factor with replication). Abnormal sensation in the distribution of the mental nerve was reported by 22 patients in 34.2% of the sides tested 3 months after surgery. At 6 months’ time following surgery 12 patients reported altered sensation in 13.2% of the sides tested. By 3 and 6 months the test values for moving 2pntD and LTS were statistically significant different when compared with preoperative values. Patients with 4 implants were significantly more likely to develop abnormal function of the trigeminal nerve than patients with 2 implants. The factors gender and age showed no significant difference in the outcome of the different psychophysical tests. The discrepancy in outcome between subjective reports on asking and psychophysical tests was as to be expected but could also suggest a high satisfaction with the implant surgery performed. This study has shown that the prevalence of altered sensation following mandibular implant surgery may be higher than previously thought. Further prospective studies are required to more accurately document the complication of altered sensation following mandibular implant surgery. Does intraoperative nerve encounter and other parameters influence the inferior alveolar nerve function after sagittal split ramus osteotomy of the mandible? Anders Westermark, Hans Bystedt & Lars von Konow. Department of Maxillofacial Surgery, Karolinska
Hospital, Stockholm, Sweden. Direct trauma to the Inferior Alveolar Nerve (IAN) during Sagittal Split Ramus Osteotomy (SRO) of the mandible has been claimed to be responsible for postoperative neurosensory dysfunction of the lower lip and chin area. The relatively high frequency of such neurosensory dysfunction described in the literature makes it a disquieting drawback of the surgical procedure. Tearing of the nerve due to mandibular advancement and nerve compression due to various types of osteosynthesis also have been suggested to cause reduced IAN function after SRO. Influence of patient’s age and sex also has been mentioned. In an analysis of IAN function of 496 mandibular sides operated on with SRO the nerve function 2 years after surgery was correlated to a series of parameters including patient’s age and sex, degree of intraoperative nerve encounter/damage, degree of mandibular advancement, type of osteosyhthesis and experience of the surgeon. The sensibility of the lower-lip and chin area was determined by light touch perception and was divided into fully normal sensibility, almost normal and reduced sensibility. Of the operated sides 59.7% demonstrated fully normal sensibility; 20.8% almost normal and 19.5% reduced sensibility. The patient’s age was significantly correlated to the degree of neurosensory dysfunction and the surgeon’s experience also seemed to influence the neurosensory function after SRO. However, the degree of intraoperative nerve encounter/damage did not correlate to the degree of IAN dysfunction nor did parameters such as degree of mandibular advancement and type of osteosynthesis. Based on our findings which will be presented in detail we suggest that the soft tissue dissection on the medial aspect of the mandibu-
lar ramus might be co-responsible for the neurosensory dysfunction observed after SRO. The possible derangements:
role of the mandibular condyle in painful MRI findings. J. Widelec & J. Van Reck*.
internal
MRI and CT Unit Department of Medical Imaging, lnstitut Bordet, Brussels; *Department of Maxillo-facial Surgery, Hopital Universitaire Saint-Pierre Brussels.
Two-hundred MRI studies (400 TMJ) were analysed. Each patient underwent a standard MRI study including both joints with sagittal and coronal views. Whenever no explanation for the pain was found an additional sequence (T2 or T2*) were used to look within the bone marrow of the mandibular condyle. Twenty non symptomatic volunteers were also studied in the conditions. One patient was studied 6 months after orthognathic surgery (Dal Pont procedure). One patient had a follow-up study after splint therapy. This patient was no longer symptomatic. Joint effusion, internal derangement of the TMJ and pain are strongly linked. That is the reason why those patients were excluded. A pattern of bone marrow edema (BME) of the mandibular was observed in 20 patients. The condyle appears with a low signal intensity on the spin-echo Tl weighted images (SETlWl) and with a very high intensity on the T2 weighted images. BME is often associated with severe degeneration of the disk or disk displacements without reduction. In one patient BME was associated with a presumed chondromatosis synovialis and in another one with an osteochondritis dissecans of the condyle. Such pattern was also observed in other joints like the hip. Similarities with the hip are also observed: same evolution of the signal intensity, the reversibility of this signal abnormality under adequate treatment. The result of the follow-up study demonstrates a total recovery of the normal signal of the condyle. Repetitive microtrauma and change of the load of the condyle after orthognathic surgery are probably the cause of the signal abnormalities. In conclusion, several observations support the hypothesis that the condyle can play a role in the onset of the pain in internal derangements, However the problem of the pain is multifactorial and this study probably gives a part of the answer. CYPZD6 poor metaboliser genotype and oral squamous noma. Stephen F. Worrall. University of Keele
cell carci-
School Postgraduate Medicine North Staffordshire Hospital, UK.
of
The CYP2D6 gene is a member of the Cytochrome P450 multigene superfamily which like other P450 genes codes for the production of mono-oxygenase enzymes involved in the phase I activation of many substrates including putative oral carcinogens. CYP2D6, located on the long arm of chromosome 22 is polymorphic as a result of frameshift mutations to introns or intron/exon boundaries. Such polymorphisms are expressed phenotypically as either extensive metabolisers (EM, homozygous or heterozygous wild type), or poor metabolisers (PM, deletion of both functional alleles). The population frequency of the PM genotype amongst Caucasians is low, between 5 and 7%. Because of its central role in putative oral carcinogen activation and the potential for individual carcinogenesis susceptibility variation resulting from polymorphism. CYP2D6 polymorphism was studied in a population of patients with established oral carcinoma. Blood samples were taken from patients presenting to the Joint Oncology Clinic at the North Staffordshire Hospital and the DNA extracted using a standard Phenol/ Chloroform technique. CYP2D6 specific primers were used in a standard PCR technique followed by restriction enzyme digestion to isolate the CYP2D61 and CYP2D62 alleles. The resulting PCR/ digest product was then separated into its component parts by agarose gel electrophoresis. Compared to the population norm of 5-7%, the patient DNA had a PM rate of 25%. A highly significant increase. Because all patients were already entered onto the departmental computer oral cancer database it was possible to obtain their clinical history including stage, smoking and alcohol intake. Surprisingly, in one particular sample run, all patients found to be PM also had extensive oral mucosal dysplasia with multifocal malignant change! These results, if confirmed by future ongoing work are of great interest as they throw into doubt the currently held belief that the P450
Abstracts enzymes are necessary for toxin/carcinogen activation. Hopefully, by the September 1996 meeting I will be in a position to present CYP2D6 data from over 100 archival oral squamous cell carcinoma tissue blocks as well as more peripheral blood samples. I will either confirm or refute the current data on CYP2D6 PM genotype status and oral cancer susceptibility.
Lower third molar surgery morbidity - do senior house officers improve with experience in their resident year? A. Zachariah, T K. Ong & A. Fordvce. Maxillofacial Unit, Newcastle General Hospital, Newcastle Upon Tyne, UK. Senior house officers (SHOs) in oral and maxillofacial surgery remove lower third molars throughout their resident year. It has been shown that the morbidity rate of this common procedure is influenced by the surgeon’s experience (Journal of Oral und MaxiNofacid Surgery 1986; 44: 8.55). Therefore, the morbidity rate should improve as the SHOs become more experienced. We studied the morbidity rate of all lower third molar surgery (under local anesthesia + /- sedation and general anesthesia) carried out by 5 SHOs in the first and last quarter of their resident year. There were a total of 591 patients (1110 lower third molars). There was no permanent nerve dysaesthesia. The Table below summarises the morbidity rates. Table 1st quarter (No. of patients) Transient Lingual Inferior nerve Infection
Dysaesthesia nerve 81302 (2.6%) alveolar 61302 ( 1.9’:/;1) 68:302
(22.5%)
2nd quarter (No. of patients)
1 I,‘289 (3.8%) 4/289 ( I .3’%) JJ./289
In conclusion, there was no significant between the two periods studied.
(26.6%)
difference
Total (No. of patients)
191591 (3.2%) IO.!591 ( 1.6%) 1451591 in morbidity
(24.5%) rates
Traumatic optic nerve injury - an animal model and its implications for clinical research. M. Zerfotvski, N.-C. Gellrich, M.-M. Gellrich, E. Machtens & U. T. Easel. Department of Oral and Maxillofacial Surgery and Department of Neurophysiology of the RuhrUniversity Bochum, Germany. Apart from the complete severance of the optic nerve, the pathogenesis of blindness due to skull base fractures is poorly understood. Likewise therapeutic options remain to be elucidated.
269
We developed an animal model of traumatic optic nerve injury that is easy to handle, reproducible and quantifiable. This is a prerequisite for studies on the pathogenesis and therapy of visual impairment due to skull base trauma. Rat optic nerves were microsurgically exposed and traumatized by a special compression device (5 to 20 cN/mm’ for 1 to 30 min) (n= 150). In a second model an inflatable microballoon catheter was inserted behind the ocular bulb. saline instilled (0.220.5 ml). and left in place for 60 or 90 min. imitating retrobulbar hematoma. Rats were sacrificed after 30 days. Retinae were whole-mounted and optic nerves cross-sectioned for histologic and morphometric work-up. Optic nerve compression resulted in a loss of retinal ganglion cells and in changes of cell size. Optic nerves showed a corresponding reduction of axons, There was approx. an inverse linear relationship of retinal ganglion cell numbers and time or pressure. The second (balloon) model gave considerably less predictable results.
Soft palate reconstruction using a superiorly based pharyngeal flap. A. Zuy&m & J. S. Brown. Regional Maxillofacial Unit, Walton Hospital. Liverpool, UK. Speech and swallowing problems due to velopharyngeal incompetence may follow soft palate resection and reconstruction. Over the past 3 years we have developed the use of a superiorly based pharyngeal flap in conjunction with a radial forearm flap for soft palate reconstruction. We present our early results from a longitudinal comparative study involving 17 consecutive patients with malignant disease of the oral cavity in which a partial or total soft palate resection was required. Speech and swallowing function were assessed by patient questionnaire and videoflouroscopy using our rating scale of velopharyngeal function. The combination of the superiorly based pharyngeal and radial forearm flap results in improved speech and swallowing following three quarter and total soft palate resection. Our early results suggest that the introduction of functional tissue to the nonfunctioning flap results in a clinical improvement for the patient.