Limitations of peritoneal lavage with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding

PURPOSE: Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model. METHODS: Mtln3 adenocarcinoma cell viability was testedin vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine.In vivo, Fischer rats were inoculated with 10⁵ or 10⁶ cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, providone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times. RESULTS: Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10⁵ or 10⁶ tumor cellsin vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 10⁵ or 10⁶ cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weightor high molecular weight, three times for one and five minutes, after inoculation of 10⁶ cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10⁵ tumor cells were soiled, no toxicity was observed and the tumor take was reduced to 30 percent (P<0.05). CONCLUSIONS: Povidone-iodine toxicity proved to be a major issuein vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the inoculum size of exfoliated or soiled cancer cells is limited.     

Malignant pheochromocytoma: current status and initiatives for future progress

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multi-center studies.     

Release of cardiac troponin I after temporally graded acute coronary ischaemia with electrocardiographic ST depression

BACKGROUND: Elevation of cardiac biochemical markers and ST segment depression in the electrocardiogram have important roles in the risk stratification of unstable coronary syndromes. We assessed graded duration of acute coronary ischaemia with ST depression versus release of cardiac troponin I (cTnI) and conventional cardiac markers in 15 ischaemic pigs and 11 controls. METHODS: Coronary ischaemia was induced via percutaneous technique by semiinflating an angioplasty balloon in the left circumflex artery. Blood velocity monitored by Doppler was reduced until ST depression > or =0.1 mV was obtained. Among 26 pigs, six controls had jugular vein sheath introduced only, five controls jugular vein and bilateral femoral sheaths, and 15 pigs were divided into three equal groups (n=5) in which ischaemia was maintained for 10, 20 and 30 min, respectively. RESULTS: Mean blood flow velocity (cm/s) at baseline was 16.3+/-6.5 and was reduced to 4.1+/-3.2 (25% of normal, range 20-29%) during ischaemia. cTnI (microg/l) did not increase in controls but increased from 0.05 to 0.52 (P<0.05) and 0.76 (P<0.05) with 10 and 20 min of ischaemia, and to 30.77 (P<0.05) with 30 min of ischaemia. A rise of myoglobin and conventional cardiac enzymes did not distinguish controls with arterial cut-down from the ischaemia groups. CONCLUSION: Release of cTnI depends on the duration of ST depression ischaemia. The critical time for a major release seems to be between 20 and 30 min. Thus, very early intervention in patients with prolonged ST depression ischemia should be focused on in future clinical trials.     

Investigation of the Mechanical Properties of Mn-Alloyed Tin-Silver-Copper Solder Solidified with Different Cooling Rates

Manganese can be an optimal alloying addition in lead-free SAC (SnAgCu) solder alloys because of its low price and harmless nature. In this research, the mechanical properties of the novel SAC0307 (Sn/Ag0.3/Cu0.7) alloyed with 0.7 wt.% Mn (designated as SAC0307-Mn07) and those of the traditionally used SAC305 (Sn96.5/Ag3/Cu0.5) solder alloys were investigated by analyzing the shear force and Vickers hardness of reflowed solder balls. During the preparation of the reflowed solder balls, different cooling rates were used in the range from 2.7 K/s to 14.7 K/s. After measuring the shear force and the Vickers hardness, the structures of the fracture surfaces and the intermetallic layer were investigated by SEM (Scanning Electron Microscopy). The mechanical property measurements showed lower shear force for the SAC0307-Mn07 alloy (20–25 N) compared with the SAC305 alloy (27–35 N), independent of the cooling rate. However, the SAC0307-Mn07 alloy was softer; its Vickers hardness was between 12 and 13 HV, whereas the Vickers hardness of the SAC305 alloy was between 19 and 20 HV. In addition, structural analyses revealed rougher intermetallic compound layers in the case of the SAC0307-Mn07 alloy, which can inhibit the propagation of cracks at the solder–substrate interface. These two properties of SAC0307-Mn07 alloy, the softer nature and the rougher intermetallic layer, might result in better thermomechanical behavior of the solder joints during the lifetime of electronic devices.