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Biomedical subjects

M A Clark

Publications and source records attributed to M A Clark.

At least 19 recordsLinked to original sources
PubMed2006

Surgical management of soft tissue sarcoma in patients over 80 years.

AIMS: To report outcome on patients over 80years of age with soft tissue sarcoma (STS), with respect to surgical treatment, co-morbidity, complications and survival. METHODS: From a prospective database of 3400 patients with STS presenting over a 13-year period, all patients over 80years of age were identified and reviewed, with respect to tumour characteristics morbidity, mortality and outcome. RESULTS: 128 patients over 80years were treated for STS with 63 referred for treatment of primary disease, of whom 50 underwent resectional surgery. The remaining 65 patients were treated for recurrent or incompletely excised disease. Of the 50 patients treated primarily with surgery, 56% of tumours where high grade and 56% were greater than 10cm in diameter. The overall complication rate was 34%, with a 30-day mortality of 4%. Two- and 5-year survival rates were 56% and 46%, with a local recurrence rate of 22% at a mean follow-up of 22months. CONCLUSION: This patient group presented with poor prognosis tumours that were associated with poor outcomes in the medium to long term. Age need not be considered a contra-indication to radical surgery with curative intent.

Age Factors↗
PubMed2006

Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes.

IGF-binding protein (IGFBP)-3 is generally considered to have actions that counterbalance those of IGFs and is therefore being developed as a cancer treatment. In breast tumors, however, high levels are associated with aggressive tumors and poor prognosis. Consistent with this we have demonstrated that although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells cultured on collagen or laminin, it promoted their attachment and survival on fibronectin, which is abundant in the matrix of aggressive tumors. We have now examined the factors that determine whether IGFBP-3 has positive or negative actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T cells in the presence of an antibody to the beta1-integrin subunit or when cholesterol-stabilized complexes were disrupted. These actions were blocked by IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar actions on MCF-7 cells that were again reversed on fibronectin or with disruption of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody. In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells, but these effects were again reversed on fibronectin and blocked by the beta1 antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins, enhancing their aggregation, the recruitment of focal adhesion kinase, and the activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes.

Apoptosis↗
PubMed2006

The outcome of surgery in fulminant Clostridium difficile colitis.

BACKGROUND: The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases. METHODS: We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996-2003 in our Unit. RESULTS: The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra-operatively) survived after a prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.

Adult↗
PubMed2005

Delay in referral to a specialist soft-tissue sarcoma unit.

BACKGROUND: Soft-tissue sarcoma is a rare neoplasm which can occur almost anywhere in the body. There are no specific symptoms and signs and the disease can mimic more common benign and malignant conditions. It is not surprising, therefore, that diagnosis and referral to a specialist unit is often delayed. METHODS: A prospective audit was undertaken in 216 patients referred to a specialist unit with suspected or proven soft-tissue sarcoma over a 12 month period. All patients were interviewed to determine the chronology of symptoms and signs, and the referral and diagnostic pathway. Delay in referral was defined as three months or greater from first presentation to a doctor to review at our unit. RESULTS: There were 159 patients with previously untreated soft-tissue sarcomas. Thirty-one patients had delays in referral, and the overall median delay was 14 months (range 4-96 months). The delay was caused by the general practitioner in 13 patients, the patient (after general practitioner referral) on two occasions, by the hospital or referring specialist in seven patients, and was multifactorial in nine patients. CONCLUSIONS: A fifth of patients with soft-tissue sarcoma encountered important delays in referral to this specialist unit. This duration of delay is likely to have had a detrimental effect on treatment options and outcomes, including survival in some patients.

Adult↗
PubMed2005

Surgical management of primary and recurrent retroperitoneal liposarcoma.

BACKGROUND: Surgery plays a dominant role in the initial and subsequent treatment of retroperitoneal liposarcoma (RPLS). This study was a review of outcomes of patients treated at the Royal Marsden Hospital. METHODS: Records of all patients who had surgery for RPLS since 1990 were reviewed, with particular attention to local recurrence and disease-specific survival. Patients with primary RPLS and those with recurrent RPLS, who had palliative surgery after a variable number of operations performed elsewhere, were considered separately. RESULTS: Seventy-two patients had surgery for primary RPLS, over half of whom underwent resection of a contiguous organ to achieve clearance. Follow-up of at least 12 months was available for 58 patients. Thirty-four patients had no evidence of recurrence after median follow-up of 26 (range 12-151) months. Low-grade tumour and macroscopic clearance of tumour were significantly associated with a reduced risk of local recurrence and improved survival. Forty-seven patients had palliative surgery for recurrent RPLS. Median survival from time of last operation to death was 27 (range 0-79) months. Follow-up was to a median of 68 (range 14-261) months. CONCLUSION: Patients with low-grade RPLS that has been completely resected at the initial operation have the most favourable prognosis. Palliative resection is worthwhile to treat troublesome symptoms of recurrence.

Adult↗
PubMed2005

Jejunal Crohn's disease is associated with a higher postoperative recurrence rate than ileocaecal Crohn's disease.

OBJECTIVE: Crohn's disease is a chronic inflammatory, panintestinal disease of uncertain aetiology. The recurrence rate of Crohn's disease, often taken as the time when further surgical procedure is undertaken, has been reported to be as high as 76% in 10 years. The site of the disease has not yet been associated with the recurrence rate of Crohn's disease. The aim of the study was to compare the outcome of patients who were surgically treated for jejunal Crohn's disease to those whose diseases was confined to the ileocaecal region. METHOD: The information was tracked from our database of 724 surgically treated Crohn's disease patients between 1943 and 2002. Twenty-eight patients with jejunal Crohn's disease at their first operation (12 jejunum alone, 16 also involving other sites) were identified. For each of these patients, 3 patients with ileocaecal Crohn's, matched for age, sex, and smoking habits (n = 84) were identified as controls. RESULTS: The median age in both groups was 21 years (range 16-52 years) with a median follow-up period of 19 years. The 3, 5 and 10 years re-operation rate for the groups with jejunal disease were 43%, 50% and 61% compared to 22%, 30% and 51% with ileocaecal disease, respectively. CONCLUSIONS: The presence of jejunal Crohn's disease is associated with a higher rate of early disease recurrence compared to ileocaecal disease but long-term recurrences rate do not differ significantly.

Adolescent↗
PubMed2005

Pedicled flaps in the treatment of nonhealing perineal wounds.

INTRODUCTION: A persistent sinus is an annoying complication following proctectomy. We examined the experience of a single colorectal surgeon in treating this condition using pedicled flaps. METHODS: Case note review of all patients undergoing gracilis muscle transposition, Rectus abdominis muscle flap or omental flap for persistent perineal sinus. RESULTS: Seventeen patients were identified: seven had gracilis muscle transposition, eight had omental transposition and two had a rectus abdominis flap. 13/17 patients who underwent a flap had a persistent sinus following proctectomy for Inflammatory bowel disease. Four patients who had a gracilis muscle transposition achieved healing. Seven out of eight patients had good results with omental transposition. One patient did well after a rectus abdominis flap. CONCLUSIONS: A gracilis transposition is a relatively simple operation with minimal morbidity useful for superficial sinuses not requiring a muscle bulk. A rectus abdominis flap is a more complex specialized procedure with better results especially in dealing with larger cavities but it may compromise future stoma sites. Omentoplasty has excellent results, but is only available in some patients.

Adult↗
PubMed2004

Management of in-transit metastases from cutaneous malignant melanoma.

BACKGROUND: In-transit metastases from cutaneous malignant melanoma (cutaneous or subcutaneous deposits between the primary melanoma and regional lymph nodes) represent late-stage disease, and their treatment should be tailored accordingly. This article reviews the pathology, clinical significance and treatment options for in-transit disease from melanoma. METHODS: An initial Medline search was undertaken using the keywords 'melanoma and in-transit' and 'melanoma and non-nodal regional recurrence'. Additional original articles were obtained from citations in articles identified by the initial search. RESULTS AND CONCLUSION: In-transit metastases carry a poor prognosis. The method of treatment should be tailored to the extent of cutaneous disease. The first line of treatment remains complete excision with negative histopathological margins. There is no need for wide excision. Carbon dioxide laser therapy is valuable for multiple small cutaneous deposits. Isolated limb perfusion has a role for numerous or bulky advanced in-transit metastases in the limbs that are beyond the scope of simpler techniques. Systemic chemotherapy has response rates of about 25 per cent and is reserved for patients for whom surgery is no longer feasible.

Amputation, Surgical↗
PubMed2004

Duration of pneumoperitoneum on chest radiograph after open colorectal surgery.

BACKGROUND: Postoperative pneumoperitoneum on a plain chest radiograph is a potentially important medicolegal document of possible complication. However, pneumoperitoneum may be observed without significance after intra-abdominal procedures. METHODS: Between April 2001 and March 2002, 204 consecutive open laparotomies for colorectal surgery were studied. Sixty-three patients had 97 chest radiographs taken before the twenty-fifth postoperative day. RESULTS: Only one patient had subdiaphragmatic air (height >20 mm) on the tenth postoperative day associated with a visceral perforation. Normal subdiaphragmatic pneumoperitoneum was observed on 11 films in 8 patients (13%). Small amounts of air (<15 mm high) were observed in 7 (15%) of 47 radiographs on days 0-5, in 4 (18%) of 25 radiographs on days 6-10, but in no radiograph of 24 after day 10. CONCLUSIONS: Subdiaphragmatic pneumoperitoneum less than 20 mm high is often observed between the sixth and tenth postoperative days, without clinical importance.

Colectomy↗
PubMed2004

Elastofibroma: a rare soft tissue tumour with a pathognomonic anatomical location and clinical symptom.

BACKGROUND: Elastofibromas are rare benign soft tissue tumours that are almost always located at the inferior pole of the scapula, deep to the serratus anterior muscle. Their anatomical location and a distinctive clinical symptom distinguish them from malignant soft tissue tumours. PATIENTS AND METHODS: A prospective histo-pathological database of all soft tissue tumours referred for treatment to the Royal Marsden Hospital between 1995 and 2003 was searched. Seven patients treated in this institution with a histological diagnosis of elastofibroma were identified. RESULTS: The usual presenting symptoms were that of a mass at the angle of the scapula (7/7), and clunking of the scapula on shoulder abduction (5/7). Pain was an infrequent symptom (1/7). Imaging by CT or MR usually indicated an indeterminate soft tissue neoplasm deep to the peri-scapular muscles, but the histological diagnosis was confirmed pre-operatively by core biopsy in all patients. Subsequent surgical excision was only performed if symptoms were severe. CONCLUSIONS: The clinical presentation of these benign neoplasms is typical and the suspected clinical diagnosis can be confirmed easily by core biopsy. Surgery can be safely reserved for symptomatic patients.

Aged↗
PubMed2004

Selective lymphadenectomy in sentinel node-positive patients may increase the risk of local/in-transit recurrence in malignant melanoma.

AIM: To determine whether sentinel lymph node biopsy (SLNB) for cutaneous malignant melanoma, particularly when followed by selective lymphadenectomy (SL) if involved nodes are found, alters the incidence of local/in-transit recurrence. METHODS: A literature overview of SLNB with or without SL has been performed, concentrating on the reported site(s) of first recurrence, and with specific reference to the incidence of local/in-transit recurrence. This is compared to the incidence after wide local excision (WLE) alone. RESULTS: The incidence of local/in-transit recurrence after WLE alone is 2.5-6.3% over a given range of tumour thickness, and is 9.0% after SLNB (with or without SL). In the latter group, the local/in-transit recurrence rate is 5.7% following SLNB alone in SN-negative patients, and is 20.9% after SLNB plus SL in SN-positive patients. CONCLUSIONS: The incidence of local/in-transit recurrence following selective lymphadenectomy in sentinel node-positive patients may be greater than four times the incidence expected. This possible iatrogenic risk should be confirmed or refuted by randomised controlled trial. Until then the SLNB procedure should be regarded as experimental and not performed outside validation trials.

Humans↗
PubMed2004

Stewart-Treves syndrome--treatment and outcome in six patients from a single centre.

AIMS: Stewart-Treves syndrome is an angiosarcoma associated with long-standing lymphoedema, most commonly seen as a rare complication of breast cancer treatment, and is associated with a poor outcome. We present results from six patients supporting the use of early radical surgery to improve prognosis. METHODS: Six patients with Stewart-Treves syndrome were diagnosed and treated at our centre over an 11-year period. Five patients had forequarter amputation and the sixth had a through-hip amputation. RESULTS: Four of the six patients are alive and well following surgery (at 3, 16, 23, and 135 months after amputation); one patient died from metastatic disease at 15 months and the second died due to an unrelated malignancy. CONCLUSION: Early diagnosis and treatment by radical ablative surgery confers a reasonable prognosis with this rare but aggressive disease. A nihilistic approach is unjustified.

Aged↗
PubMed2004

Reliability of radiographic measurement of small intestinal length.

OBJECTIVE: The capacity for absorption of nutrients after small intestinal resection is related to the remaining length of intestine, and short bowel syndrome has major implications. Accurate pre-operative determination of bowel length may be useful in conditions where further resection of small bowel is contemplated. The aim of this study is to evaluate the accuracy of small bowel length measured by barium follow-through (BaFT) examination. PATIENTS AND METHODS: Twenty-two patients underwent both intra-operative measurement of small bowel length, and BaFT examination where length was measured using an opisometer. RESULTS: The difference between operative and radiological measurement (mean +/- standard deviation: 15.7 +/- 16 9%) was least in those with the shorter small intestine (overall variation: r = 0.703, P < 0.01, regression coefficient: -0.118, intercept: 15.1). There was no difference in whether BaFT was performed pre or postoperatively. CONCLUSION: Assessment of small bowel length by BaFT radiography is accurate, particularly in those with shorter small bowel lengths.

Adult↗
PubMed2004

Long strictureplasty is as safe and effective as short strictureplasty in small-bowel Crohn's disease.

BACKGROUND: For the past 20 years it has been shown that intestinal strictureplasty is safe and effective in the management of short strictureplasty. Long strictureplasty (> 20 cm) may be an alternative to resection in some patients, especially in diffuse disease or after previous extensive resections. We reviewed the outcome of long strictureplasty for Crohn's Disease, to examine safety and recurrence rates, compared with conventional short strictureplasty. METHODS: Sixty-two patients have undergone single strictureplasty for jejunoileal Crohn's disease since 1974. Median follow-up was 121 (range 7-253) months. Twenty-one operations involved a single long strictureplasty, and 41 operations had a single short strictureplasty. RESULTS: No significant differences were identified between the groups. The postoperative complications in long strictureplasty included 2 abscesses only and after short strictureplasty there was one anastomotic leak and one postoperative abscess. The median hospital stay was 10 days after long strictureplasty and 9 days after short strictureplasty. Three-, 5- and 10-year disease-free rates for long and short strictureplasty, respectively, were 3-year 80.4% and 62.1%; 5-year 55.2% and 49.8% and 10-year 49.1% and 33.5% (NS). CONCLUSIONS: These data indicate that long strictureplasty is safe and produces equivalent results to conventional (short) strictureplasty.

Adolescent↗
PubMed2003

Major amputation for soft-tissue sarcoma.

BACKGROUND: Advances in oncological practice have reduced the number of major amputations performed for soft-tissue sarcoma, but this remains a valuable, if infrequent, option for both curative and palliative indications. METHODS: A review of patients and case-notes was carried out from the prospective sarcoma database at the Royal Marsden Hospital. RESULTS: Over a 10-year interval, 40 major amputations (18 forequarter, 17 hindquarter and five through hip) were performed, predominantly for disease recurring after previous limb-conserving surgery (31 of 40). A wide variety of soft-tissue sarcoma subtypes was seen; they were often large (more than 10 cm; 18 of 40) or multifocal (six), usually high grade (25), and frequently proximal or involving neurovascular structures such that limb salvage was precluded. Median range age of the patients was 59 (17-87) years. The operative 30-day mortality rate was zero. Hospital stay was a median of 10.5 days for forequarter amputation, and 19 days for hindquarter and through-hip amputation. Local recurrence occurred in ten patients, six of whom had concurrent distant metastases. Twenty-seven patients were alive (20 disease free) at a median follow-up of 12 months, nine of whom were alive without evidence of disease beyond 2 years. Ten patients died after a median of 7.5 months; three survived more than 2 years. CONCLUSION: Major amputation is a useful procedure in carefully selected patients with soft-tissue sarcoma.

Adolescent↗
PubMed2002

Soft-tissue tumours of the perineum.

AIM: Primary perineal tumours in adults are rare entities that have been infrequently reported (one clinical series of nine patients with sarcoma and isolated case reports). We present our experience of perineal tumours better to characterize and define the natural history of this condition. METHODS: Perineal tumours occurring in adults (>18 years) from January 1990 were identified from the Royal Marsden Hospital's Sarcoma Unit prospective database. RESULTS: Nineteen perineal soft-tissue tumours (12 malignant and seven benign) were evaluated and treated at the Royal Marsden Hospital during this period. Liposarcoma (n=3) and aggressive angiomyxoma (n=4) were the most frequent histological subtypes. Three malignant and four benign tumours were larger than 10 cm. Most tumours were located deep to the deep fascia. Local recurrence in those with sarcoma occurred in one of five patients with negative microscopic margins and in one of two patients who had positive microscopic margins. One patient each with aggressive angiomyxoma and fibromatosis recurred locally. CONCLUSION: Aggressive treatment in the form of wide local excision is associated with fewer local recurrences in adults with primary perineal soft-tissue tumours. The aim of surgical treatment should be to obtain negative resection margins without causing disturbance to urinary or anorectal function.

Adolescent↗