Microvascular histopathology in head and neck oncology

Transcription

1 British Journal of Plastic Surgery (2003), 56, q 2003 The British Association of Plastic Surgeons. Published by Elsevier Science Ltd. All rights reserved. doi: /s (03) Microvascular histopathology in head and neck oncology S.D. Stavrianos, N.R. McLean, S. Fellows, P.D. Hodgkinson, A. Kostaki, C.G. Kelly and J.V. Soames The Northern Head and Neck Cancer Unit, The Freeman Hospital, Newcastle-upon-Tyne, UK SUMMARY. A histological study of both recipient and flap vessels was performed in 30 patients with head and neck cancer, and relevant preoperative risk factors were assessed. A total of 35 free flaps were transferred in 30 patients; 16 patients had preoperative radiotherapy, 13 were smokers, eight had hypertension and six had peripheral vascular. No significant venous pathology was found in either the flap or the neck veins. However, over two-thirds of the neck arteries and one-half of the flap arteries were found to have microscopic arterial pathology. The only pre-existing factor significantly influencing vessel pathology was hypertension (P ¼ 0:007). All flaps survived, although in two there was some loss of the skin paddle. This study reveals that the majority of patients undergoing microsurgery in the head and neck region have pre-existing arterial damage in both the flap and the recipient arteries, but this does not have a significant effect on the overall patency of the microvascular anastomoses. q 2003 The British Association of Plastic Surgeons. Published by Elsevier Science Ltd. All rights reserved. Keywords: head and neck neoplasms, microvascular anastomosis, risk factors, histopathology. Advances in reconstructive techniques, with the use of free microvascular flaps, allow for large en-bloc resections with complex one-stage reconstruction. Such techniques may also permit more effective adjuvant treatment in terms of postoperative brachytherapy. Despite the refinement of microvascular techniques over the last 30 years, some anastomoses still fail owing to technical errors or pre-existing vascular. However, the effect of pre-existing medical conditions and radiotherapy on small-vessel pathology has not yet been fully elucidated. 1 3 The purposes of this study were to investigate the microvascular histopathology of head-and-neck and flap vessels in a group of patients with malignant, and to clarify the importance of any pre-existing risk factors that could influence vessel patency in routine head and neck reconstructive procedures. Materials and methods We prospectively studied 30 patients undergoing resection of head and neck malignancies and immediate reconstruction. The tissues normally discarded during vessel trimming or fashioning the opening for an endto-side anastomosis provided the specimens for analysis. Arterial and venous samples from both the donor and Presented at the Summer Meeting of the British Association of Plastic Surgeons, July 1999, Belfast, UK. the recipient sites were histologically examined for vessel pathology, and preoperative risk factors, such as smoking, diabetes and hypertension, were recorded. All flaps were examined daily until the patient was discharged from hospital and thereafter at the combined head and neck clinic at 1 month. Tumours were staged according to the TNM classification of the American Joint Committee on Cancer (AJCC), and all radiotherapy treatments were given as teletherapy, using a photon beam. Statistical methods In order to evaluate the effect of the various pre-existing risk factors on the microvascular pathology, the data were analysed using bivariate analysis techniques applying the x 2 test. In order to analyse the effect of the various pre-existing medical conditions and the effect of radiotherapy on the appearance of postoperative complications in patients who had undergone extensive tumour resection, a bivariate analysis was used to test the significance of each single factor using the x 2 test. After this, a multivariate analysis was applied. A random model of logistic regression was then used to evaluate the simultaneous effects of the various risk factors. All of the analyses were carried out by the Department of Statistics at the University of Athens using the Statistical Package for Social Sciences (SPSS v. 10.1) for Windows software (SPSS Inc, USA). 140

2 Microvascular histopathology in head and neck oncology 141 Table 1 Anatomical site of malignancy Table 3 Extent of surgical resection oral cavity 12 parotid 5 orbit 3 mandible 2 scalp 2 petrous 1 neck 1 sphenoid 1 pharynx 1 Larynx 1 skull 1 Results Table 2 Results of x 2 tests between the appearance of headand-neck small-vessel pathology and the various risk factors P Number of patients with the risk factor Frequency of severe histology problems with the risk factor (%) free of the risk factor (%) preoperative radiotherapy age.60 years hypertension alcohol smoking chemotherapy a cardiac a cerebrovascular a renal a diabetes a peripheral vascular a a The results of these tests are only indicative, since the number of patients with the risk factor is very low. mandibulectomy 11 segmental 7 marginal 4 craniofacial 10 pharyngolaryngectomy 3 radical parotidectomy 2 glossectomy 2 petrosectomy 1 neck skin 1 Of the 30 patients studied, 22 were male and eight were female, and their mean age was 59 years (range: years); 19 patients presented with recurrent (63%). The locations of the tumours are shown in Table 1: 40% were intraoral malignancies and 17% were in the parotid gland. There were 22 (73%) advanced T4 tumours and four T2 and three T3 malignancies (one patient had reconstruction for osteoradionecrosis). Eleven patients presented with clinically positive nodes. Preoperative risk factors included alcohol use (57%), radiotherapy (53%), tobacco use (43%), hypertension (27%), cardiac (10%), chemotherapy (10%), cerebrovascular (7%), renal (7%), diabetes (3%) and peripheral vascular (3%) (Table 2). Surgical resection included mandibulectomy or craniofacial resection in the majority of cases (70%) (Table 3), and 23 patients underwent neck dissection. The histological diagnoses of the tumours are listed in Table 4, the commonest being squamous cell carcinoma (63%), followed by soft-tissue sarcomas (10%). Negative histological margins were achieved in 63% of cases, and a total of 35 free flaps were transferred (five patients required a double synchronous reconstruction). The commonest flap used was the radial forearm flap (RFF) (60%), followed by the deep circumflex iliac artery (DCIA) flap (17%) (Table 5). In five patients there was a complex full-thickness facial defect requiring double skin and bone reconstruction: a DCIA osseocutaneous flap and a RFF were used. The mean flap ischaemic time was 64 min (range: min) and there were no free flap failures. In all, 33 flaps survived completely and there were two partial skin losses: a DCIA flap with 50% loss of skin and an osseocutaneous RFF with 5% loss of the cutaneous paddle. In the first of these, only mild intimal thickening was seen in the flap and neck vessels, but the patient had undergone preoperative radiotherapy and was a heavy smoker. The second patient required an endarterectomy at the time of surgery, developed a haematoma postoperatively and also required a revision of the anastomosis. A total of 35 arterial and 55 venous anastomoses were performed, the commonest donor veins being the internal jugular (n ¼ 21) and the facial (n ¼ 17). The most frequent neck arteries used were the facial (n ¼ 15) and the external carotid (n ¼ 7). All of the arterial anastomoses were end-to-end, as were the venous anastomoses, except those to the internal jugular vein, which were fashioned in an end-to-side manner. From these 90 anastomoses, a total of 137 blood-vessel samples were suitable for microscopic examination (63 arteries and 74 veins). At the time of surgery, macroscopic arterial pathology (vessel-wall thickening or calcification) was noted in 13 patients (43%). One artery delaminated at the time of microvascular anastomosis, and an endarterectomy was required. On histology, no significant venous pathology was found in either the flap or the neck veins. However, just over two-thirds of the neck arteries (73%) and onehalf of the flap arteries (57.5%) were found to have Table 4 Tumour histology squamous cell carcinoma 19 sarcoma 3 basal cell carcinoma 2 malignant melanoma 1 sphenoid meningioma 1 anaplastic carcinoma 1 pleomorphic salivary adenoma 1 malignant peripheral nerve-sheath tumour 1 radiotherapy necrosis 1

3 142 British Journal of Plastic Surgery microscopic arterial pathology. Of the 30 head and neck arterial specimens suitable for microscopic examination, eight had some degree of diffuse or focal intimal thickening, one had atheromatous changes and 13 had a combination of intimal thickening and/or calcification and/or duplication or fragmentation of the internal elastic lamina (Fig. 1). Eight specimens had no specific abnormality. In this study the only risk factor having a significant influence on head and neck microvascular histopathology was hypertension (P ¼ 0:007) (Table 2). Of the 33 flap arterial specimens suitable for microscopic examination, 10 had some degree of diffuse or focal intimal thickening and nine had a combination of intimal thickening and/or calcification and/or duplication or fragmentation of the internal elastic lamina; 14 vessel specimens had no specific abnormality (Fig. 1). When the preoperative risk factors were analysed to assess their potential effect on postoperative complications, it was found that smoking and the presence of severe histological changes in the head and neck vasculature were statistically significant factors (Table 6). To evaluate the simultaneous effects of the various risk factors, a multivariate analysis was applied to estimate the probability of the appearance of postoperative complications in the group. This showed that pre-existing vascular pathology in the head and neck region was the most important factor influencing postoperative complications and that smoking as a risk factor was only highly significant when there were coexisting histological changes (Table 7). Discussion The chance of complications arising after microvascular surgery increases with age. 4 This is no longer considered to be only a sign of age, 3 since advanced chronological age does not compromise the technical success of microvascular free tissue transfer. 5 7 In this study, two-thirds of the head and neck arteries and one-half of the flap arteries were found to have significant vascular pathology. Although increasing age corresponds with increasing likelihood of histological change, it has no significant effect per se on flap success rate. Smoking has been reported to affect the vascularity of pedicled flaps because it causes fibrosis in the intima. 8 Complications in smokers undergoing free tissue transfer may occur not at the anastomosis but at the interface between the flap and its bed or an overlying graft. 9 In this series, smoking had no significant effect. Diseases such as diabetes, hypertension and arteriosclerosis are considered to be significant risk factors in microsurgery. 10 Hypercholesterolaemia without macroscopic changes, in combination with the trauma of surgery, will lead to the accelerated formation of atherosclerotic changes. Atheromata in small arteries present technical surgical difficulties, and success depends upon the skill and experience of the surgeon. 2 Several studies have shown that the significant irreversible damage caused by radiotherapy is not sufficient, in itself, to cause a microvascular transfer to fail. Previous radiotherapy and surgery can make Table 5 Type of free flap reconstruction radial forearm 21 deep circumflex iliac artery 6 rectus abdominis 4 latissimus dorsi 2 jejunum 2 neck and vessel dissection and subsequent microvascular anastomoses more technically demanding. However, meticulous planning and proper technique ensure that patients with head and neck cancer who receive radiotherapy are at no greater risk of postoperative wound-healing or flap complications when well-vascularised tissue is brought in by free tissue transfer Preoperative radiotherapy does not affect the success of the microvascular anastomosis or overall flap survival, but it does affect the vascular integrity of the recipient bed. 14 In this study, severe intimal thickening was observed in all hypertensive patients, in patients that received preoperative chemotherapy and in patients over 70 years of age, as well as in the only diabetic patient. In addition, the great majority of smokers and drinkers and those that had received preoperative radiotherapy showed intimal thickening. Calcification and/or fibrofatty plaques were seen in all patients over 70 years of age and in the majority of hypertensive patients. Our analyses suggest that hypertension is the only factor that significantly affects small-vessel pathology in the Table 6 Results of x 2 tests between the appearance of postoperative complications and the various risk factors P Number of patients with the risk factor Frequency of postoperative complications with the risk factor (%) without the risk factor (%) severe histological changes in headand-neck vessels preoperative radiotherapy age.60 years hypertension a alcohol a smoking chemotherapy b cardiac b cerebrovascular b renal b diabetes b peripheral vascular b a Though P. 0:05; the results are indicative that these factors exhibit a slight significance, given the limited sample size. b The results of these tests are only indicative, since the number of patients with the risk factor is very low.

4 Microvascular histopathology in head and neck oncology 143 Figure 1 (A) Normal radial artery (H and E; 45); (B) normal radial artery (elastic van Gieson; 45); (C) radial artery showing focal intimal thickening (elastic van Gieson; 9); (D) radial artery showing focal intimal thickening (elastic van Gieson; 45); (E) facial artery showing focal calcification on the internal elastic lamina, which shows irregular duplication (HandE; 45); (F) facial artery showing focal calcification (arrow) on the internal elastic lamina, shows irregular duplication (elastic van Gieson; 90); (G) facial artery showing extensive calcification along the internal elastic lamina (HandE; 18); and (H) facial artery showing extensive calcification along the internal elastic lamina (elastic van Gieson; 18).

5 144 British Journal of Plastic Surgery Table 7 Probability of the appearance of postoperative complications head and neck (P ¼ 0:007). Severely disturbed vascular histology in the head and neck, and smoking are risk factors for postoperative complications, such as partial loss, wound breakdown and postoperative haematoma. An interesting finding on multivariate analysis was that smoking is a risk factor that is highly significant only when serious vascular histological changes exist in the head and neck region. The combination of factors is important for the patient s overall risk. In conclusion, despite a significant number of flap and donor arteries in the present study having both microscopic and macroscopic pathology, there was no demonstrable effect of this on the overall patency or success rate of microvascular free tissue transfer. However, there are two distinct risk zones following microsurgical procedures, the microvascular anastomosis and the downstream microcirculation, both of which exhibit a distinct pathophysiology. Future research into preventing failure following microvascular surgery needs to investigate therapeutic agents targeting both zones that will, when combined with meticulous techniques, provide further protection for complex one-stage reconstructions. 15 References Estimated probability none smoker without histology problems histology problems and non-smoker smoking and histology problems Simpson KH, Murphy PG, Hopkins PM, Batchelor AG. Prediction of outcomes in 150 patients having microvascular free tissue transfer to the head and neck. Br J Plast Surg 1996;49: Van Gelder PA, Klopper PJ. Microvascular surgery and d recipient vessels. Surgery 1981;90: Shibahara T, Schmelzeisen H, Noma H. Histological changes in vessels used for microvascular reconstruction in the head and neck. J Craniomaxillofac Surg 1996;24: Chick LR, Walton RL, Reus W, Colen L, Sasmor M. Free flaps in the elderly. Plast Reconstr Surg 1992;90: Shestak KC, Jones NF. Microvascular free tissue transfer in the elderly patient. Plast Reconstr Surg 1991;88: Bridger AG, O Brien CJ, Lee K. Advanced patient age should not preclude the use of free flap reconstruction for head and neck cancer. Am J Surg 1994;168: Malata CM, Cooter RD, Batchelor AG, et al. Microvascular free tissue transfers in the elderly: the Leeds experience. Plast Reconstr Surg 1996;98: Reus WF, Colen LB, Straker DJ. Tobacco smoking and complications in elective microsurgery. Plast Reconstr Surg 1992;89: Lee MS. Effects of nicotine on blood flow and patency of experimental microvascular anastomosis. Plast Reconstr Surg 1987;80: Ohtsuka H, Kamiishi H, Saito H, Masatsugu J, Shoiya N. Successful free flap transfers with d recipient vessels. Br J Plast Surg 1976;29: Mulholland S, Boyd JB, McCabe S, et al. Recipient vessels in head and neck microsurgery: radiation effect and vessel access. Plast Reconstr Surg 1993;92: Bengston BP, Schusterman MA, Baldwin BJ, et al. Influence of prior radiotherapy on the development of post operative complications and success of free tissue transfer in head and neck reconstruction. Am J Surg 1993;166: Keiner JL, Hoffman WY, Mathers SJ. Influence of radiotherapy on microvascular reconstruction in the head and neck region. Am J Surg 1991;162: Singh B, Gordeiro PG, Santamaria E, et al. Factors associated with complications in microvascular reconstruction of the head and neck defects. Plast Reconstr Surg 1999;103: Johnson PC, Barker JH. Thrombosis and antithrombotic therapy in microvascular surgery. Clin Plast Surg 1992;19: The Authors S. D. Stavrianos MD, Consultant Head and Neck/Plastic and Reconstructive Surgeon Head and Neck Unit, Department of Plastic and Reconstructive Surgery, Greek National Anti-Cancer Institute, St Savvas Hospital, Athens, Greece N. R. McLean MD, FRCS, Consultant Head and Neck/Plastic and Reconstructive Surgeon P. D. Hodgkinson PhD, FRCS(Plast), Consultant Head and Neck/ Plastic and Reconstructive Surgeon Department of Plastic and Reconstructive Surgery, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK S. Fellows RGN, Dip HE, Head and Neck Research Sister C. G. Kelly MB, ChB, MRCP, FRCR, Consultant Clinical Oncologist Northern Centre for Cancer Treatment, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK Professor J. V. Soames PhD, FRCPath Department of Oral Pathology, Newcastle Dental Hospital, Newcastle upon Tyne NE2 4BW, UK A. Kostaki MSc, PhD, Assistant Professor Department of Statistics, Athens University of Economics and Business, Athens, Greece Correspondence to Mr N. R. McLean, Associate Professor of Surgery, University of Adelaide, South Australia Paper received 29 August Accepted 10 December 2002.