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Biomedical subjects

D S Soutar

Publications and source records attributed to D S Soutar.

At least 19 recordsLinked to original sources
PubMed2006

The unexpected sites of melanoma regional recurrences.

UNLABELLED: Sentinel node biopsy is a means of identifying nodal involvement in melanoma and lymphoscintigraphy identifies unpredictable sites of melanoma sentinel nodes in up to 25% of cases. Whilst there is a dearth of recent publications in this area, it nevertheless remains an interesting observation that unpredictable sites of sentinel nodes are so common as to be accepted as normal. This study was performed to determine if this high rate of unpredictable lymphatic drainage was reflected in clinical practice, where therapeutic lymph node dissections were performed for pathologically confirmed regional disease. METHODS: Patients undergoing regional lymph node dissections for histologically proven malignant melanoma were identified from a computer database. Patient details were analysed from case records. RESULTS: Two hundred and forty-three case records were examined and 237 were suitable for analysis. The site of the primary was the head and neck in 50 (21%), trunk in 73 (31%), upper limb in 27 (11%) and lower limb in 87 (37%). In 15 cases (6%), the first site of regional disease was unpredictable. In these 15 cases, the site of the primary was the head and neck in two, trunk in 11, upper limb in one and lower limb in one. In 37 cases (16%), a subsequent site of nodal recurrence was unpredictable. Clinicians should be aware that patients with melanomas, particularly of the trunk, especially those in whom a therapeutic nodal dissection has been performed, may have nodal disease at unpredictable sites. However, unexpected sites of regional disease are not as common as sentinel node biopsy would suggest. Guidelines for lymph node examination in cutaneous melanoma are suggested based on these findings.

Female↗
PubMed2005

The nodal neck level of sentinel lymph nodes in mucosal head and neck cancer.

Sentinel node biopsy is emerging as a successful means of identifying subclinical lymph node disease in mucosal head and neck cancer. Sentinel node studies in melanoma and breast cancer have identified sentinel nodes at unusual sites and the technique is redefining our understanding of dynamic lymphatic flow. In this study, the sentinel nodes in mucosal head and neck malignancies were mapped according to their site within the neck and this was correlated with tumour site within the oral cavity. Fifty-two necks were explored for sentinel nodes from tumours located in the tongue (23 cases), floor of mouth (12 cases), palate (six cases), retromolar trigone (five cases), alveolus (three cases), buccal mucosa (two cases), tonsil (two cases) and lip (one case). In total, 124 sentinel nodes were found in levels I-V. Two hot spots were found in the tonsils and were not excised, two nodes were located in level IIB, four nodes were found in level IV, three in the contralateral neck and one in level V. The sentinel nodes located at unusual sites would not have been excised in a supraomohyoid neck dissection and the study has improved our understanding of dynamic lymph flow from tumours.

Head and Neck Neoplasms↗
PubMed2004

Histological changes in radial forearm skin flaps in the oral cavity.

We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The "changed" flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy.

Adult↗
PubMed2004

Improved staging of cervical metastases in clinically node-negative patients with head and neck squamous cell carcinoma.

BACKGROUND: The management of the N0 neck in oral and oropharyngeal cancer is often determined by the risk of metastases related to features of the primary tumor. Where the risk of metastases is >20%, elective neck dissection (END) has been advocated. This study reviewed clinical staging, surgical staging, pathologic staging, and histopathologic parameters to determine the prediction of nodal metastases and micrometastases in patients with head and neck squamous cell carcinoma. METHODS: A prospective series of 61 clinically neck node-negative patients undergoing surgical resection of a T1/2 intraoral or oropharyngeal invasive squamous cell carcinoma and surgical staging of the neck, with sentinel node biopsy (SNB) alone or SNB-assisted END, between June 1998 and March 2002 were included in this study. RESULTS: Pathologic upstaging of the clinically N0 neck occurred in 27 (44%) of 61 patients. Routine pathology with hematoxylin and eosin upstaged disease in 22 of 27 patients (sensitivity of 81%). Five patients with micrometastasis were staged pN1mi after stepped serial sectioning and immunohistochemistry. Tumor thickness, a noncohesive invasive front, and perineural and bone invasion were all histological predictors for cervical metastases. Five patients with micrometastases were staged pN1mi. CONCLUSIONS: Both clinical staging and routine pathologic staging underestimate the presence of nodal metastases. Staging with either SNB alone or SNB-assisted END shows promise in the management of the N0 neck by identifying patients with micrometastases (pN1mi).

Carcinoma, Squamous Cell↗
PubMed2003

The impact of immunohistochemistry on sentinel node biopsy for primary cutaneous malignant melanoma.

Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal disease in patients with malignant melanoma. Superselection of pathological nodes has allowed improved pathological staging of disease. The aim of this study was to look at the impact of immunohistochemistry on pathological staging of sentinel nodes. The first 100 patients undergoing SNB for primary cutaneous malignant melanoma were included in this study. Sentinel node harvesting was performed with the aid of preoperative lymphoscintigraphy and the intraoperative use of both a gamma probe and blue dye. If the sentinel nodes contained tumour on either routine pathology or immunohistochemistry, patients were offered a therapeutic lymph node dissection (TLND). Patients underwent no other treatment to the primary lymph node basin if the sentinel node was free of metastases. In all, 95 patients had at least one node identified, and 25 were staged SNB positive and offered subsequent TLND. We found that 76% (19/25) of SNB positive patients were staged positive on routine pathology, and 24% (6/25) were staged with immunohistochemistry. Immunohistochemistry upstaged disease in 8% of patients (6/76). In all, 21 of the patients staged positive with SNB underwent TLND; 50% (8/16) of the patients staged sentinel node positive with routine pathology showed no further disease in the TLND, compared with 100% (5/5) of the patients staged sentinel node positive with immunohistochemistry only (P<0.05). Three patients have developed recurrence within the nodal basin following a negative SNB. The sensitivity of the procedure is currently 89% (25/28), with a mean follow-up of 24 months. Immunohistochemistry is an essential part of identifying micrometastasis in sentinel nodes, upstaging 8% of patients in our series. Patients with micrometastatic disease may well have a different prognosis from those with occult disease, and careful delineation of these patients is required to determine the prognostic influence of micrometastasis.

Humans↗
PubMed2003

To thin or not to thin: the use of the anterolateral thigh flap in the reconstruction of intraoral defects.

The anterolateral thigh (ALT) flap has achieved popularity recently for free-flap reconstruction of intraoral defects following excision of squamous cell carcinoma. We have assessed the feasibility of the ALT flap as a free flap for oral lining and the potential use of the thinned ALT flap in a one-stage reconstruction. We used the ALT flap to reconstruct the oral cavity in 18 consecutive patients between December 2000 and December 2001 following intraoral resection of squamous cell carcinoma. Twelve patients underwent reconstruction using a standard ALT flap, four patients received a thinned ALT flap in a one-stage procedure, one patient received a standard ALT flap in combination with a fibula flap and one patient received a combination of a standard ALT flap and vascularised iliac bone. There were no complications in any of the 14 cases in which a standard ALT flap was used. Two of these flaps were thinned subsequently as secondary procedures. Of the four thinned ALT flaps, one flap failed completely and two flaps experienced partial necrosis. In all but one case the donor site was closed directly with minimal donor-site morbidity. The ALT flap is a versatile flap that can be used in combination with other flaps for more complex defects with minimal donor-site morbidity and is a useful alternative in the armamentarium of the head and neck surgeon. Thinning of the flap is best performed as a secondary procedure, should it be required.

Aged↗
PubMed2002

The First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer and adoption of a multicenter trial protocol.

BACKGROUND: Sentinel node biopsy (SNB) is a new technique in staging the clinically N0 neck. On June 25 and 26, 2001, the First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer took place in Glasgow, United Kingdom. METHODS: Twenty-two centers contributed results on the use of SNB as a staging tool in head and neck squamous cell carcinoma. The pathology of the sentinel node was compared with that of the pathologic neck specimen. RESULTS: Three hundred sixteen clinically N0 necks were included. Sentinel nodes were identified in 301 necks (95%). Of these 301 necks, 76 necks were staged positive with SNB, and 225 were staged negative. The overall sensitivity of the procedure was 90%. Centers who had performed < or = 10 cases had a lower sensitivity (57%), discovering only 4 of 7 metastatic nodes, in comparison with 72 of 77 metastatic nodes discovered for centers that had performed >10 cases (sensitivity, 94%). CONCLUSIONS: The cumulative results of all those who contributed to the first international conference confirm that there is a role for SNB for staging the clinically N0 neck, and it has a similar sensitivity to that of a staging neck dissection.

Carcinoma, Squamous Cell↗
PubMed2002

The learning curve for sentinel node biopsy in malignant melanoma.

Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal micrometastasis in cutaneous melanoma. In order to assess our learning curve, we compared our first 30 cases with our subsequent 30 cases. A total of 60 patients underwent SNB for cutaneous melanoma, using preoperative lymphoscintigraphy together with the intraoperative use of a Neoprobe and Patent Blue V dye. At least one sentinel node was identified in 93% of patients (90% in our first 30 cases; 97% in our subsequent 30 cases). Sentinel nodes contained tumour in 21% of cases. Of the sentinel nodes that contained tumour in the first 30 cases, 87% were identified by Neoprobe examination and 60% using blue dye. In the second 30 cases, the tumour-containing sentinel nodes were identified in all cases by both the Neoprobe and the blue dye. The sentinel node appeared to be the only involved node in 71% of patients. In the first 30 patients, one patient with a negative sentinel node developed nodal recurrence. These data confirm the feasibility of the sentinel-node technique in cutaneous melanoma. However, there is a learning curve, and the technique should be performed only by limited numbers of people with suitable training.

Clinical Competence↗
PubMed2002

The ability of lymphoscintigraphy to direct sentinel node biopsy in the clinically N0 neck for patients with head and neck squamous cell carcinoma.

This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct sentinel node biopsy (SNB) in the identification of occult metastases in the clinically N0 neck for patients with head and neck squamous cell carcinoma (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma probe and blue dye. SNB was performed after radiocolloid and blue dye injection. Pre-operative LSG and the intra-operative use of a gamma probe identified radioactive sentinel nodes, and visualization of blue stained lymphatics identified blue sentinel nodes. 104 sentinel nodes were harvested from 43 patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested, 17 of 62 (27%) nodes identified as both radioactive and blue were positive for occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39 (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05). LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC.

Carcinoma, Squamous Cell↗
PubMed2001

The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck.

BACKGROUND: Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck. METHODS: Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection. RESULTS: Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16. CONCLUSIONS: The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered.

Adult↗
PubMed2001

Treatment of oral cancer: the need for defined protocols and specialist centres. variations in the treatment of oral cancer.

The authors of this study aimed to identify treatment philosophies for oral cancer within the west of Scotland and to investigate any survival differences associated with the various treatment options by means of a retrospective review of case notes and cancer registry data. All patients with squamous cancer of the tongue or floor of the mouth were identified from the West of Scotland Cancer Registry for the period 1984-1990. A total of 206 patients were available for study. Five different treatment protocols were identified: 5% of patients underwent biopsy only, 16% biopsy plus radiotherapy, 11% excisional biopsy, 25% radical surgery, and 42% radical surgery plus radiotherapy. Tumour staging by the TNM classification was an important factor that determined outcome. When adjusting for T stage and nodal involvement, there was a significant effect of treatment protocol on both the disease-free period (P < 0.001) and on survival (P < 0.001). The treatment options were used differently by individual clinicians and were related to stage of the disease. One hundred and forty-four (70%) of the patients were treated by a single combined head and neck unit based within the plastic surgery unit at Canniesburn Hospital. The remaining 62 were treated in 13 different units throughout the west of Scotland. For those not treated in the combined head and neck unit, the increased hazard for recurrence was 1.43 (95% confidence interval (CI) 1.01-2.02), and the increased hazard ratio for death was 1.48 (95% CI 1.06-2.06) when adjusting for tumour stage, and nodal involvement. Treatment philosophies for oral cancer have a significant effect on outcome. There is a need to develop clearly defined protocols based on staging and site of disease. We believe that treatment should be carried out within a multidisciplinary setting in a combined head and neck cancer unit.

Adult↗
PubMed2001

Increasing dietary supervision can reduce weight loss in oral cancer patients.

Weight loss after treatment for intraoral malignancy is common and can impair patient recovery and wound healing. We report a reduction in weight loss in patients undergoing combined-modality treatment (surgery + radiotherapy) after an increase in dietary supervision and changes to the patient dietary protocol. Two groups of patients were compared: Group I received treatment before the protocol changes, and Group II received treatment after the changes took effect. After surgery the average weight loss for Group I was 3.67% compared with 2.42% for Group II (P < 0.05), after radiotherapy the average weight loss for Group I was 6.56% compared with 4.83% for Group II (P < 0.05), and after combined-modality treatment the average weight loss for Group I was 9.83% compared with 6.6% for Group II (P < 0.05). The successful protocol changes included increased supervision of patients by the dedicated head-and-neck team dietitian when patients were undergoing radiotherapy, including the period between completion of surgery and commencement of radiotherapy. The period of time spent without specialist dietary supervision was therefore reduced. Specific guidelines were devised to allow for increased dietary input when required, specifically, if patients lost weight for > or = 2 wk or if they were being fed enterally. These changes were made after an audit that demonstrated that severe weight loss in this group of patients was common. We have demonstrated that regular appraisal of weight loss in this group of patients is valuable and that this weight loss can be reduced if appropriate action is taken.

Adult↗
PubMed2000

Current role of gene therapy in head and neck cancer.

Our increasing knowledge of cancer molecular biology has led to the development of new genetic therapies for the treatment of cancer. Such therapies are advantageous in that they can selectively target tumour tissue leaving normal tissue relatively unaffected. In squamous cell cancer of the head and neck, such therapies may be beneficial in the treatment of loco-regional recurrence, minimal residual disease and in the treatment of distant metastatic disease. This article describes the principles of cancer gene therapy reviews some early clinical trials of gene therapy in head and neck cancer.

Adenoviridae↗
PubMed2000

p53 alterations in recurrent squamous cell cancer of the head and neck refractory to radiotherapy.

The aim of the study was to determine the incidence of p53 alterations by mutation, deletion or inactivation by mdm2 or human papillomavirus (HPV) infection in recurrent squamous cell cancer of the head and neck (SCCHN) refractory to radiotherapy. Twenty-two tumours were studied. The p53 status of each tumour was analysed by sequencing of exons 4-9 and by immunohistochemistry. Mdm2 expression was assessed by immunohistochemistry and HPV infection was assessed by polymerase chain reaction of tumour DNA for HPV 16, 18 and 33. Fifteen (68%) of the 22 tumours studied had p53 mutations, while seven had wild-type p53 sequence. p53 immunohistochemistry correlated with the type of mutation. HPV DNA was detected in 8 (36%) tumours and all were of serotype HPV 16. Of these, five were in tumours with mutant p53 and three were in tumours with wild-type p53. Mdm2 overexpression was detected in 11 (50%) tumours. Of these, seven were in tumours with mutant p53 and four were in tumours with wild-type p53. Overall, 21 of the 22 tumours had p53 alterations either by mutation, deletion or inactivation by mdm2 or HPV. In this study, the overall incidence of p53 inactivation in recurrent head and neck cancer was very high at 95%. The main mechanism of inactivation was gene mutation or deletion which occurred in 15 of the 22 tumours studied. In addition, six of the seven tumours with wild-type p53 sequence had either HPV 16 DNA, overexpression of mdm2 or both which suggested that these tumours had p53 inactivation by these mechanisms. This high incidence of p53 dysfunction is one factor which could account for the poor response of these tumours to radiotherapy and chemotherapy. Therefore, new therapies for recurrent SCCHN which either act in a p53 independent pathway, or which restore p53 function may be beneficial in this disease.

Adult↗
PubMed2000

Natural history and patterns of recurrence of tongue tumours.

This retrospective study comprises 226 patients with squamous cell carcinoma of the tongue treated at Canniesburn Hospital, Glasgow between 1980 and 1996. The male:female ratio was 1.2:1 and the average age was 64 years. The ratio of anterior 2/3 to posterior 1/3 tongue lesions was 1.8:1. A total of 23% of patients were clinically staged as T1, 50% were T2 and 27% were T3/T4. At presentation 156 patients (69%) had a clinically negative neck, while 110 patients (49%) had a neck dissection at the time of treatment of the primary. A comparison between the clinical and pathological T and N stages highlighted the difficulties of clinical TNM staging with upstaging of the primary T stage in 21% of patients and downstaging in 6% and upstaging of neck disease in 36% and downstaging in 7.7%. The incidence of clinically occult disease in the neck was 41% including six patients (4.5%) with occult disease in the contralateral neck.

Adult↗
PubMed2000

A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer.

An E1B 55 kDa gene-deleted adenovirus, Onyx-015, which reportedly selectively replicates in and lyses p53-deficient cells, was administered by a single intratumoral injection to a total of 22 patients with recurrent head and neck cancer. The objectives of this Phase I study were to determine the safety, feasibility, and efficacy of this therapy and determine any correlation to p53 status. Six cohorts were investigated with a dose escalation from 10(7)-10(11) plaque-forming units. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA and neutralizing antibody to adenovirus. Tumor biopsies were taken to detect adenovirus by in situ hybridization. Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached at the highest dose of 10(11) plaque-forming units. Twenty-one of the 22 patients treated showed an increase in neutralizing antibody to adenovirus. In situ hybridization showed viral replication in 4 of 22 patients treated, all of whom had mutant p53 tumors. Using conventional response criteria, no objective responses were observed. However, magnetic resonance imaging scans were suggestive of tumor necrosis at the site of viral injection in five patients, three of whom were classified using nonconventional criteria as partial responders, and two of whom were classified using nonconventional criteria as minor responders. Of these five cases, four had mutant p53 tumors. The response duration for the three partial responders was 4, 8, and 12 weeks. An additional eight patients had stable disease in the injected tumors lasting from 4-8 weeks. These preliminary results show that intratumoral administration of Onyx-015 is feasible, well tolerated, and associated with biological activity. Further investigation of Onyx-015, particularly with a more frequent injection protocol and in combination with systemic chemotherapy, is warranted.

Adenovirus E1B Proteins↗