- Email: [email protected]
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma; a prospective study
ABSTRACTS
1161
Results: The results for 20 colonoscopists were reviewed. ‘Clinical Performance’ was compared by plotting individual ‘Caecal Intubation Rates’ (CIR) against Number of Points/List. In total, 7578 procedures were performed with a mean of 8.2 Points/List, and included 3873 colonoscopies. The mean CIR was 90.1% which is above the JAG standard of 90%. The results are summarised below. The list running costs are equivalent to 4 colonoscopies, or 8 points. Number of colonoscopists (n ¼ 20)
Above JAG standard (CIR) Below JAG standard (CIR)
8 Points/List
Income generated to meet costs
Below
Above
Below
Above
3 7
7 3
0 3
10 7
Interestingly, the colonoscopists who performed the most procedures/ list were also those offering the most training opportunities (r2 0.41 cf. 0.04; linear regression analysis). Conclusions: Clinical effectiveness is a function of both clinical standards and efficient use of resources. The most clinically effective colonoscopists are the most likely to offer training opportunities. 20. The avß6 integrin - a novel target for antibody conjugated magnetic fluid hyperthermia for therapy in squamous cell carcinoma Daniel Marsha, H. Kogelbergb, K. Vigorb, Q. Pankhurstc, J. Chanaa, K. Chesterb a Royal Free Hospital, Pond Street, London, NW3 2QG b Cancer Institute, UCL London c London Centre of Nanotechnology Introduction: Magnetic fluid hyperthermia (MFH) is a novel technique whereby superparamagnetic iron oxide nanoparticles (SPIONs) are placed within and excited by an alternating magnetic field to generate heat.1 This approach for cancer therapy has previously been demonstrated in patients using direct intratumoural injection of SPIONs.2,3 We propose MFH can be delivered more effectively using antibody-targeted SPIONs. To test this hypothesis we have developed a recombinant single chain antibody fragment (scFv) to deliver SPIONs to the epithelial restricted avß6 integrin, an exciting new target in head and neck cancers.4 Methods/Results: Using a rational structural based approach we engineered MFE-23, a well characterized scFv reactive with carcinoembryonic antigen (CEA), to create a new humanized avß6-reactive scFv. The new scFv was cloned with a free c-terminal cysteine for site specific attachment to SPIONs and produced in the yeast P.pastoris. The novel scFv specifically binds avß6 ligand on ELISA and is a potent inhibitor of avß6-mediated cell adhesion. In parallel experiments, we have developed a method of delivering MFH sufficient to heat several commercially available SPIONs and established methods for SPION-scFv chemical attachments. Optimisation of experimental protocols to assess hyperthermic potential of the scFv-SPION complexes will be discussed along with the feasibility and limits of MFH for therapy in head and neck squamous cell carcinoma. Conclusions: A new recombinant scFv reactive with avß6 has been designed and manufactured. The scFv is biologically active and is currently being investigated for delivery of SPION targeted MFH specifically to squamous cell carcinoma. References 1. Alexiou C, et al. J Nanosci Nanotechnol 2006 SepeOct;6(9e10): 2762e8. 2. Maier Hauff K, et al. J Neuro Oncol 2007 Jan;81(1):53e60. 3. Johannsen M, et al. Int J Hyperthermia 2007 May;23(3):315e23. 4. Ramos DM, et al. Matrix Biol 2002;21:297e307. 21. Profit or loss in endocrine surgery? Olumuyiwa Olubowale, J. Weaver, B. Harrison Royal Hallamshire Hospital, Glossop Road, Sheffield, S2 10JF
Introduction: National tariffs for endocrine surgical procedures: KO1 (thyroid)-£2125.00, KO2 (parathyroid)-£1997.00 and KO3 (adrenal)£3225.00 do not account for case complexity, time for teaching and other variables. This study analysed the financial shortfall of payment by tariff over a 12-month period in an endocrine surgical service at a University Teaching Hospital. Methods: Detailed cost analysis of endocrine surgical operations over a 12-month period including operating department time, length of hospital stay, and theatre consumables was done. Results: 157 thyroid, 64 parathyroid and 26 adrenal procedures were performed as below: 1. Thyroid lobectomy (47%), total thyroidectomy for benign disease (40%), total thyroidectomy and major neck node dissection for malignancy (13%). 2. Parathyroidectomy for primary HPT (49%), renal HPT (43%) and re-operative parathyroidectomy for (8%). 3. Laparascopic adrenalectomy for phaechromocytoma (28%), Cushing’s (48%), Conns (16%) and other conditions (8%). Actual costs per case were as follows: KO1
KO2 KO3
Lobectomy
Total thyroidectomy
£2,329 PHPT £1,997 Conns £3,676
£4,323 Re-operative £5137 Cushings £7,283
Total thyroidectomy and major node dissection £6,809 Renal HPT £8,034 Phaeo £9,589
The actual costs minus tariff payment resulted in an annual deficit of £521,803. Conclusion: Payment by tariff for endocrine surgical procedures was substantially lower than costs incurred. Tariff payment does not adequately reimburse for complex cases. Operating department time (£1038 per hour) and length of stay (£240 per night) account for most of the deficit. 22. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma; a prospective study Faheez Mohamed, H. Yano, T. Cecil, B. Moran NSCAG Pseudomyxoma Centre, North Hampshire Hospital, Aldermaston Road, Basingstoke, Hampshire, RG24 9NA Introduction: Peritoneal mesothelioma is rare, but increasing in frequency. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. We report the early outcomes of the first 17 patients who underwent surgery for peritoneal mesothelioma at our institution using this loco-regional approach. Methods: Seventeen patients with peritoneal mesothelioma who were treated between 1998 and 2007 at our institution were identified from a prospective database. Patients underwent either complete cytoreduction or tumour debulking for palliation. HIPEC at 42 C and Early Postoperative Intraperitoneal Chemotherapy (EPIC) were performed with doxorubicin and cisplatinum in selected patients. Results: All patients but 3 (multicystic) had malignant disease of the following pathologic types: 5 well differentiated papillary, 5 epithelial, and 4 biphasic. After surgical resection, eight patients were considered to have a complete cytoreduction, eight underwent debulking and in one patient biopsies only were performed. 16 patients received HIPEC and 8 patients received EPIC. One postoperative death occurred and six major postoperative complications were recorded. Of 12 patients presenting with ascites resolution occurred in 10. At a median follow up of 13 months (range 1 to 83 months) 4 patients have no evidence of disease and 3 patients are alive with disease. Conclusions: A therapeutic strategy combining cytoreductive surgery with HIPEC appears to provide a survival benefit with improved palliation of symptoms in selected patients. It is associated with acceptable morbidity when performed by an experienced surgical team.
1161
Results: The results for 20 colonoscopists were reviewed. ‘Clinical Performance’ was compared by plotting individual ‘Caecal Intubation Rates’ (CIR) against Number of Points/List. In total, 7578 procedures were performed with a mean of 8.2 Points/List, and included 3873 colonoscopies. The mean CIR was 90.1% which is above the JAG standard of 90%. The results are summarised below. The list running costs are equivalent to 4 colonoscopies, or 8 points. Number of colonoscopists (n ¼ 20)
Above JAG standard (CIR) Below JAG standard (CIR)
8 Points/List
Income generated to meet costs
Below
Above
Below
Above
3 7
7 3
0 3
10 7
Interestingly, the colonoscopists who performed the most procedures/ list were also those offering the most training opportunities (r2 0.41 cf. 0.04; linear regression analysis). Conclusions: Clinical effectiveness is a function of both clinical standards and efficient use of resources. The most clinically effective colonoscopists are the most likely to offer training opportunities. 20. The avß6 integrin - a novel target for antibody conjugated magnetic fluid hyperthermia for therapy in squamous cell carcinoma Daniel Marsha, H. Kogelbergb, K. Vigorb, Q. Pankhurstc, J. Chanaa, K. Chesterb a Royal Free Hospital, Pond Street, London, NW3 2QG b Cancer Institute, UCL London c London Centre of Nanotechnology Introduction: Magnetic fluid hyperthermia (MFH) is a novel technique whereby superparamagnetic iron oxide nanoparticles (SPIONs) are placed within and excited by an alternating magnetic field to generate heat.1 This approach for cancer therapy has previously been demonstrated in patients using direct intratumoural injection of SPIONs.2,3 We propose MFH can be delivered more effectively using antibody-targeted SPIONs. To test this hypothesis we have developed a recombinant single chain antibody fragment (scFv) to deliver SPIONs to the epithelial restricted avß6 integrin, an exciting new target in head and neck cancers.4 Methods/Results: Using a rational structural based approach we engineered MFE-23, a well characterized scFv reactive with carcinoembryonic antigen (CEA), to create a new humanized avß6-reactive scFv. The new scFv was cloned with a free c-terminal cysteine for site specific attachment to SPIONs and produced in the yeast P.pastoris. The novel scFv specifically binds avß6 ligand on ELISA and is a potent inhibitor of avß6-mediated cell adhesion. In parallel experiments, we have developed a method of delivering MFH sufficient to heat several commercially available SPIONs and established methods for SPION-scFv chemical attachments. Optimisation of experimental protocols to assess hyperthermic potential of the scFv-SPION complexes will be discussed along with the feasibility and limits of MFH for therapy in head and neck squamous cell carcinoma. Conclusions: A new recombinant scFv reactive with avß6 has been designed and manufactured. The scFv is biologically active and is currently being investigated for delivery of SPION targeted MFH specifically to squamous cell carcinoma. References 1. Alexiou C, et al. J Nanosci Nanotechnol 2006 SepeOct;6(9e10): 2762e8. 2. Maier Hauff K, et al. J Neuro Oncol 2007 Jan;81(1):53e60. 3. Johannsen M, et al. Int J Hyperthermia 2007 May;23(3):315e23. 4. Ramos DM, et al. Matrix Biol 2002;21:297e307. 21. Profit or loss in endocrine surgery? Olumuyiwa Olubowale, J. Weaver, B. Harrison Royal Hallamshire Hospital, Glossop Road, Sheffield, S2 10JF
Introduction: National tariffs for endocrine surgical procedures: KO1 (thyroid)-£2125.00, KO2 (parathyroid)-£1997.00 and KO3 (adrenal)£3225.00 do not account for case complexity, time for teaching and other variables. This study analysed the financial shortfall of payment by tariff over a 12-month period in an endocrine surgical service at a University Teaching Hospital. Methods: Detailed cost analysis of endocrine surgical operations over a 12-month period including operating department time, length of hospital stay, and theatre consumables was done. Results: 157 thyroid, 64 parathyroid and 26 adrenal procedures were performed as below: 1. Thyroid lobectomy (47%), total thyroidectomy for benign disease (40%), total thyroidectomy and major neck node dissection for malignancy (13%). 2. Parathyroidectomy for primary HPT (49%), renal HPT (43%) and re-operative parathyroidectomy for (8%). 3. Laparascopic adrenalectomy for phaechromocytoma (28%), Cushing’s (48%), Conns (16%) and other conditions (8%). Actual costs per case were as follows: KO1
KO2 KO3
Lobectomy
Total thyroidectomy
£2,329 PHPT £1,997 Conns £3,676
£4,323 Re-operative £5137 Cushings £7,283
Total thyroidectomy and major node dissection £6,809 Renal HPT £8,034 Phaeo £9,589
The actual costs minus tariff payment resulted in an annual deficit of £521,803. Conclusion: Payment by tariff for endocrine surgical procedures was substantially lower than costs incurred. Tariff payment does not adequately reimburse for complex cases. Operating department time (£1038 per hour) and length of stay (£240 per night) account for most of the deficit. 22. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma; a prospective study Faheez Mohamed, H. Yano, T. Cecil, B. Moran NSCAG Pseudomyxoma Centre, North Hampshire Hospital, Aldermaston Road, Basingstoke, Hampshire, RG24 9NA Introduction: Peritoneal mesothelioma is rare, but increasing in frequency. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. We report the early outcomes of the first 17 patients who underwent surgery for peritoneal mesothelioma at our institution using this loco-regional approach. Methods: Seventeen patients with peritoneal mesothelioma who were treated between 1998 and 2007 at our institution were identified from a prospective database. Patients underwent either complete cytoreduction or tumour debulking for palliation. HIPEC at 42 C and Early Postoperative Intraperitoneal Chemotherapy (EPIC) were performed with doxorubicin and cisplatinum in selected patients. Results: All patients but 3 (multicystic) had malignant disease of the following pathologic types: 5 well differentiated papillary, 5 epithelial, and 4 biphasic. After surgical resection, eight patients were considered to have a complete cytoreduction, eight underwent debulking and in one patient biopsies only were performed. 16 patients received HIPEC and 8 patients received EPIC. One postoperative death occurred and six major postoperative complications were recorded. Of 12 patients presenting with ascites resolution occurred in 10. At a median follow up of 13 months (range 1 to 83 months) 4 patients have no evidence of disease and 3 patients are alive with disease. Conclusions: A therapeutic strategy combining cytoreductive surgery with HIPEC appears to provide a survival benefit with improved palliation of symptoms in selected patients. It is associated with acceptable morbidity when performed by an experienced surgical team.