Hyperthermic Isolated Limb Perfusion with TNF α and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management of osteosarcoma was studied in the canine model

H ypertherm ic isolated lim b perfusion with TNFa and cisplatin in the treatm ent of osteosarcom a of the extrem ities: a feasibility stu dy in healthy dogs

Abstract Pur pose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-a (TNFa ) and cisplatin for the m anagement of osteosarcoma was studied in the canine m odel. M ethods. During seven perfusions in six healthy mongrel dogs (weight 32±2 kg) technical aspects of HILP under mild hyperthermia (39± 40Ê C) were studied. In ® ve experim ents HILP was perform ed with TNFa alone (0.5 mg/l extremity volume), and in two experiments TNFa was combined with cisplatin (25 mg/l extrem ity volume). During the perfusions physiological parameters were m onitored and TNFa and total cisplatin concentrations were determined. Results. Perfusion conditions (pH, PCO 2 , PO 2 ,¯ow and pressure) rem ained within physiological ranges. Three dogs died within 24 h despite a sublethal systemic concentration of TN Fa that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb. Conclusions. This feasibility study in healthy dogs dem onstrated that HILP with TNFa and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFa and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma. Key words: Osteosa rcom a of the extrem ity, hyperther m ic isolation, lim b perfusion, chem otherapy, com bination therapy, dog

Differences in sentinel lymph node pathology protocols lead to differences in surgical strategy in breast cancer patients.

Contains fulltext : 50705tjan-heijnen.pdf (publisher's version ) (Closed access)BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN). At present, therefore, various hospitals use different SN pathology protocols of which the effect has not been fully elucidated. We hypothesized that differences between hospitals in SN pathology protocols affect subsequent surgical treatment strategies. METHODS: Patients from four hospitals (A-D) were prospectively registered when they underwent an SN biopsy. In hospitals A, B, and C, three levels of the SN were examined pathologically, whereas in hospital D, at least seven additional levels were examined. In the absence of apparent metastases with hematoxylin and eosin examination, immunohistochemical examination was performed in all four hospitals. RESULTS: In total, 541 eligible patients were included. In hospital D, more patients were diagnosed with a positive SN (P < .001) as compared with hospitals A, B, and C, mainly because of increased detection of isolated tumor cells. This led to more completion axillary lymph node dissections in hospital D (66.3% of patients (P < .0001), compared with 29.0% in hospitals A, B, and C combined). Positive non-SNs were detected in 13.9% of patients in hospital D, compared with 9.7% in hospitals A, B, and C (P = .70). That is, in 52.4% of patients in hospital D, a negative completion axillary lymph node dissection was performed, compared with 19.3% of patients in hospitals A, B, and C combined. CONCLUSIONS: Differences in SN pathology protocols between hospitals do have a substantial effect on SN findings and subsequent surgical treatment strategies. Whether ultrastaging and, thus, additional surgery can offer better survival remains to be determined

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)