Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

Background Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma. Methods Following complete cytoreduction, HIPEC was performed using 460 mg/m² oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival. Results From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year. Conclusion Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.     

Tissue factor as the main activator of the coagulation system during cardiopulmonary bypass

OBJECTIVE: This study investigates the influence of foreign material and blood aspirated from nonvascular structures on activation of coagulation, hemolysis, and blood loss. METHODS: The series comprises 3 randomized groups (groups C, S, and S+P) of 10 patients undergoing routine coronary artery bypass grafting with cardiopulmonary bypass. In group C, the control group, all aspirated blood was returned into the circulation. In group S suction blood was discarded, whereas group S+P was identical to group S, with surfaces coated with phosphorylcholine. Plasma concentrations of beta-thromboglobulin, thrombin generation, haptoglobin, and free hemoglobin, as well as blood loss, were measured. RESULTS: A steady increase in free plasma hemoglobin, as well as an increased generation of thrombin, was noticed in group C. Moreover, a close correlation (r = 0.916) between the generation of thrombin and its inhibition (thrombin-antithrombin complexes) was observed. Platelets were clearly activated in group C and, to a lesser extent, in group S. In contrast, platelet activation in group S+P was negligible, resulting in a 30% decrease in blood loss (P =.05). CONCLUSIONS: Aspirated blood contaminated by tissue contact is the most important activator of the coagulation system and the principal cause of hemolysis during cardiopulmonary bypass. Contact with a foreign surface is not a main variable in the procoagulant effect of bypass. Mimicking the outer cell membrane structure resulted in decreased platelet activation and decreased blood loss.     

Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility

The fetal valproate syndrome (FVS) is characterized by distinctive facial appearance, major and minor malformations, and developmental delay. Generally, only a small proportion of prenatally exposed children are affected. The authors describe three families in whom the occurrence of FVS in all the siblings strongly suggests hereditary susceptibility to valproic acid-induced adverse outcome. The risk for recurrence in a subsequent pregnancy may be high and should be taken into account in the counseling of parents and in considering drug treatment.     

Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running

In the present study the release of proteins degrading extracellular matrix compounds to circulation was measured after damaging exercise in humans. Muscle damage was induced by downhill running; furthermore, the exercise was performed at both cold temperature (5 degrees C) and room temperature (22 degrees C) to study also the possible effect of environmental temperature on serum concentrations of matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2, and MMP-2/TIMP-2 complex, and muscle damage monitored by serum creatine kinase measurements. Results were compared with those obtained from patients having rhabdomyolysis, myositis and Becker muscular dystrophy. The present study demonstrates an acute increase in serum concentrations of MMP-9, TIMP-1, and MMP-2/TIMP-2 complex, but no changes in serum MMP-2 concentrations in response to eccentric exercise. Serum creatine kinase activity data suggest greater muscle damage after downhill running in a cold environment than at room temperature. The present observations about at most slight changes in serum MMP and TIMP concentrations and lack of their correlation to increased serum creatine kinase after exercise indicate that serum measurements of MMPs and TIMPs do not sensitively respond to exercise induced skeletal muscle damage and extracellular matrix regeneration. On the other hand, severe skeletal muscle damage, such as rhabdomyolysis, myositis and Becker muscular dystrophy, seemed to have an effect on serum MMP and TIMP concentrations.     

Substance use in pregnancy: do we care?

Two cohorts of substance-using women were compared retrospectively. From 1969 to 1979 a very high perinatal mortality rate (PMR 9.8%) was found among 92 polydrug-using women (1 twin excluded). Preterm delivery occurred in 25% of all pregnancies and in 30% of the children birth weight was below the 10th percentile. Nineteen women using heroin only had a worse fetal outcome (PMR 32%, preterm delivery in 47%, birth weight < 10th percentile in 42%). These results led to a strict surveillance system. In the period 1980–1989, 240 women (4 twins excluded) delivered after 16 weeks. Total fetal loss decreased to 2.1% and PMR to 0.4%, which was similar to results in controls. However, 22% of the women still delivered before 37 weeks and 27% delivered a child < 10th percentile. Methadone-using women were able to halve their dosage during pregnancy and 16 were detoxified. Multivariate analysis within the substance users of the second cohort showed that the neonatal abstinence syndrome, but not the (registered) amount of opiates used, was related to a lower birth weight. Not coping with prenatal care was related to a shorter pregnancy length. Multivariate analysis, including the controls, showed a significant relation of birth weight (345 g lower) with substance use. Also, head circumference was 0.8 cm smaller. Length of pregnancy however was related to smoking. This study shows that it is difficult to make substance users attend prenatal care, but also that women coping with prenatal care reduce substance intake. Opiate use might be responsible for lower birth weight, although not in a clear dose–response relationship, whereas lifestyle, as represented by not coping with prenatal care and the quantity of cigarette smoking, shortens the length of pregnancy.     

Can autologous thrombin with a rest fraction of ethanol be used safely for activation of concentrated autologous platelets applied on nerves?

The use of concentrated platelet-rich plasma (cPRP) as a source of growth factors is reported to be beneficial for an enhanced osteogenesis in spine surgery. Today both bovine and autologous thrombin is used for activating the platelets and thus releasing the growth factors. In order to prevent transmission of organisms and the development of antibodies, autologous thrombin seems to be the logical choice. However, the preparation of autologous thrombin is cumbersome and consumes a part of the cPRP. In order to overcome this problem, a commercial autologous thrombin kit (activAT, Dideco, a Sorin Group company, Italy) has been developed which produces autologous thrombin out of platelet-poor plasma. A possible disadvantage of this kit could be the rest fraction of 1.18% of ethanol in the platelet gel. In a pig model, the influence of different ethanol concentrations on the ischiadic nerve was studied. The study consisted out of four groups; a control group (n=6), a group with platelet gel 0% ethanol (n=6), a group with platelet gel 1.18% ethanol (n=6) and a group with platelet gel 3.8% ethanol (n=7). In all the groups, the ischiadic nerve was dissected and the myelin sheet opened after which the wound was closed (control group) or one of the three therapies was applied. After 12 h, the animal was sacrificed and the ischiadic nerve was submitted for histological examination. Myelin sheaths appeared normal in all cases. No axonal swelling was observed. No statistically significant differences were observed for neutrophilic and eosinophilic infiltration nor for collagen necrosis between groups. Platelet gel prepared by the use of a commercial autologous thrombin kit and containing 1.18% of ethanol can be safely used on nerves.     

Comparison of evoked electromyography and mechanical activity during vecuronium-induced neuromuscular blockade

The relationship of compound electromyography to mechanical myography was investigated in 20 patients given vecuronium in a dose of 0.1 mg kg-1. Mechanical response was affected less quickly and recovered faster than the electrical response. Although there was a good correlation between the two throughout the study, a shift towards mechanical responses was observed in all cases for the onset of blockade and recovery from blockade. Moreover, during recovery the mechanical responses became greater than the control value in all patients. This was also reflected in the statistically significant difference (P less than 0.05) of the regression lines relating tension and electromyography (TI as well as train-of-four ratio) between onset of, and recovery from, neuromuscular block.     

Response to temozolomide in second-line treatment of recurrent nonsmall cell lung carcinoma: case report

Almost all patients with stage IV nonsmall cell lung cancer (NSCLC) who show an initial response to chemotherapy will eventually relapse. For patients with a good performance status at relapse, second-line chemotherapy is a standard treatment option. A case of recurrent NSCLC described herein profiles a patient previously treated with cisplatin, irinotecan, and radical thoracic radiation for stage IIIb NSCLC. The patient showed a complete response to first-line therapy that lasted for approximately 17 months. When new adenopathy was discovered, therapy with the oral chemotherapeutic agent temozolomide was initiated. After 2 treatment cycles,a near complete response was obtained and she remained free from disease progression during all subsequent treatment cycles with temozolomide. The patient remained free from disease progression for a total of 15 months when she was treated for dehydration and a computed tomography (CT) scan showed new small bilateral pleural effusions and enlarging subcarinal, right hilar, and left infrahilar lymph nodes. The patient died 21 months after her first treatment cycle with temozolomide, most likely because of progressive disease.     

Influence of interferon on virus particle formation in different oncornavirus carrier cell lines

Three types of oncornavirus-carrying mouse cell lines were studied. Replication of endogenous sarcoma or leukemia viruses in cell lines producing the infectious viruses was as sensitive to inter feron as that of exogenous vesicular stomatitis virus (VSV). Replication of non-infectious C-type virus in S⁺L^? cells which carry a rescuable Moloney sarcoma virus (MSV) genome did not respond to interferon. However, this cell line was also found to be 70 times less responsive to interferon when tested by an exogenous VSV challenge. Finally, after exposure to interferon, M04 cells, which carry a rescuable MSV genome and produce non-infectious A-type particles, developed normal resistance to VSV. Yet, high doses of interferon could not prevent the induction of surplus A-type particles by bromodeoxyuridine (BDU) and dimethylsulfoxide (DMSO). The results are interpreted as indicating that non-infectious A-type particles are synthetized by a mechanism different from that by which infectious C-type particles are generated.