Improved survival using multi-modality therapy in patients with lung metastases from colorectal cancer: a preliminary study

This retrospective study was conducted to assess the safety, efficacy, and long-term results of multi-modality therapy including radio-frequency thermal ablation (RFA) and radiotherapy as an additional cytoreductive method for eliciting the marked effects of chemotherapy in treating unresectable lung metastases from colorectal cancer. Total of 21 patients with lung metastasis from colorectal cancer were included. They were treated with modified pharmacokinetic modulating chemotherapy (PMC). Eleven were also treated with RFA and/or radiotherapy (multi-modality group), and 10 were treated with chemotherapy alone (chemotherapy group). Characteristics and survival of patients in the multi-modality group were compared with those of the chemotherapy group. The median survival of all patients was 38.6 months after the initial PMC. The cumulative 3-year survival rate of patients in the multi-modality group was 87.5% compared with 33.3% in the chemotherapy group (p=0.0041). The course of multi-modality therapy was uneventful except for pneumothorax in those who received RFA. Although pneumothorax developed in 4 of 11 patients (36.4%) treated with RFA, all were able to receive chemotherapy within 2 weeks after RFA. In conclusion, multi-modality therapy combined with modified PMC, radiation and RFA is a feasible choice of treatment associated with reasonable morbidity and mortality in patients with inoperable lung metastases from colorectal cancer.     

Species differences in the tissue distribution of catechol and methylsulphonyl metabolites of 2,4,5,2',5'-penta- and 2,3,4,2',3',6'-hexachlorobiphenyls in rats, mice, hamsters and guinea pigs

Polychlorinated biphenyls (PCBs) are metabolized to phenolic or methylsulphonyl PCBs (MeSO(2)-CBs) in animal species. The study determined the species differences in the tissue distribution of persistent PCB metabolites in rats, mice, hamsters and guinea pigs 4 days after exposure to 2,4,5,2('),5(')-pentachlorobiphenyl (CB101) or 2,3,4,2('),3('),6(')-hexachlorobiphenyl (CB132). For CB101 metabolism, the hydroxylation in rats, mice and hamsters occurred primarily at the 3(')-position in the 2('),5(')-dichlorinated phenyl ring, whereas the hydroxylation in guinea pigs occurred preferentially at the 3-position. Metabolite profiles in tissues of hamsters were dominated by 3('),4(')-catechol-CB101, whereas metabolite profiles in rats and mice were dominated by 3(')- or 4(')-MeSO(2)-CBs. For CB132 metabolism, rats and mice produced 4(')- and 5(')-MeSO(2)-CBs at similar concentration ratios, whereas guinea pigs produced MeSO(2)-CBs at higher levels and selectively retained 5(')-MeSO(2)-CB in liver. In contrast, hamsters preferentially produced 4('),5(')-catechol-CB132 that was retained in serum. Consequently, hamsters produced catechols, whereas guinea pigs produced meta-substituted MeSO(2)-CBs, preferentially from CB132. These findings indicate that PCBs with 2,3,6-chlorine substitution are preferred substrates for the formation of catechols or MeSO(2)-CBs and the differences in metabolite profiles are related to species-dependent metabolic capacities.     

Behavior of caveolae and caveolin-3 during the development of myocyte hypertrophy

Recent studies have indicated that caveolae are enriched in a variety of signaling molecules, some of which are associated with cardiomyocyte hypertrophy. Caveolin-3, a major constituent of cardiac caveolae, has been suggested to interact with several signaling molecules. We investigated the morphologic changes of caveolae and caveolin-3 expression in hypertrophied cardiomyocytes induced by an alpha1-adrenergic agonist. Cultured rat neonatal cardiomyocytes were used for the experiments. Phenylephrine induced cellular hypertrophy associated with an increase of the number of caveolae and an up-regulation of caveolin-3. Although PMA increased the number of caveolae and the caveolin-3 expression, the extent of these up-regulations was less than that by phenylephrine. Moreover, ionomycin increased the number of caveolae and up-regulated caveolin-3 as much as phenylephrine. Phenylephrine-induced up-regulations of caveolae and caveolin-3 expression were inhibited by BAPTA, suggesting that the intracellular Ca2+ is involved in those regulations. Inhibitors of calcineurin and Ca2+calmodulin-dependent kinase II attenuated the phenylephrine-induced up-regulation of caveolin-3. In pressure-overloaded rat hearts, caveolin-3 protein levels were increased compared with sham-operated rats. In conclusion, the number of caveolae and the expression of caveolin-3 were up-regulated in rat hypertrophied cardiomyocytes, possibly via the alterations of intracellular Ca2+ and protein kinase C.     

Combination therapy with cerivastatin and nifedipine improves endothelial dysfunction after balloon injury in porcine coronary arteries

HMG-CoA reductase inhibitors and calcium channel blockers have antiatherogenic effects; however, their mechanisms remain to be elucidated. This study examined the effect of cerivastatin and/or nifedipine on the endothelial dysfunction in porcine balloon-injured coronary arteries. Normal male pigs were randomly divided into the following four groups: control, cerivastatin (1 mg/kg/d PO), nifedipine (4 mg/kg/d PO), and their combination (n = 10 each). We started the treatments 3 days before balloon injury in the proximal left coronary arteries and continued for 4 weeks after the procedure. Then, we examined endothelial vasodilator functions ex vivo in organ chambers and in vitro by Western blotting for eNOS expression. Endothelium-dependent relaxations to serotonin, but not those to bradykinin or the calcium ionophore A23187 or endothelium-independent relaxations to sodium nitroprusside, were significantly impaired by balloon injury. The monotherapy with cerivastatin or nifedipine partially improved, and their combination supernormalized the relaxations to serotonin without affecting those to bradykinin or A23187 or endothelium-independent relaxations to sodium nitroprusside. The expression of eNOS was significantly reduced by balloon injury and normalized by the combination therapy. These results indicate that the combination therapy improves endothelial dysfunction after balloon injury, in which the up-regulation of eNOS may be involved.     

Anesthetic management of a patient undergoing PTA stent placement for right common carotid artery stenosis

A 60-year-old man underwent percutaneous transluminal angioplasty (PTA) stent replacement of the right common carotid artery. Preoperative angiogram revealed bilateral vertebral artery occlusion and 50% stenosis in contralateral internal carotid artery. Anesthesia was induced and maintained with fentanyl and propofol by TCI. rSO2, BIS and EEG were monitored. Moderate hypothermia (33-35 degrees C) was induced by concomitant use of milrinone. Edaravone, a novel free radical scavenger, and Sendai cocktail were administered before interruption of carotid flow. During 5 minutes of test occlusion by balloon, right rSO2 decreased from 61% to 49% and EEG showed slow waves with decreased amplitude. Therefore we decided to perform PTA and stenting separately. Right rSO2 decreased from 62% to 48% during PTA (6 min occlusion), while rSO2 decreased from 66% to 50% during stenting (7.5 min occlusion). EEG also showed the similar changes as observed during test occlusion. After the procedures, rSO2 and EEG recovered in a short time. Postoperative angiogram showed an improvement of carotid artery stenosis and intracranial vessels showed no branch occlusion. Patient was maintained hypothermic (35 degrees C) for 2 days after surgery. He recovered without additional neurological complications. We found that rSO2 was a useful, real-time and non-invasive method for evaluation of cerebral ischemia in our patient.     

Combined paravertebral lumbar plexus and parasacral sciatic nerve block for reduction of hip fracture in four patients with severe heart failure

We experienced four cases of anesthesia for hip fracture reduction in patients with severe heart failure, where anesthesia was attempted with combined paravertebral lumbar plexus and parasacral sciatic nerve block instead of spinal anesthesia. The anesthesia was successful without any sequelae. The patients' characteristics are as follows. Case 1: 97-year-old woman with severe heart failure and old myocardial infarction. Case 2: 91-year-old man with pacemaker, heart failure and heart valve disease. Case 3: 93-year-old woman with severe heart failure and multi-vessel coronary artery stenosis. Case 4: 83-year-old woman with congestive heart failure and heart valve disease. Paravertebral lumbar plexus block was performed with Touhy needle which was directed to lumbar transverse process, then re-directed caudally. Psoas compartment was felt with loss of resistance. Twelve ml of 0.25% bupivacaine was injected. Sciatic nerve block was performed with a needle which was inserted at the midpoint between the greater trochanter and the sacral hiatus without (case 1, 2) or with nerve stimulator (case 3, 4). Eight ml of 0.25% bupivacaine was injected. During the anesthesia, propofol was injected for light sedation. Although this combined nerve block is difficult to perform compared with spinal anesthesia, this could be applicable for hip fracture reduction anesthesia, especially in patients with severe heart failure.     

Case of premature ventricular contraction immediately after electroconvulsive therapy in a depressive patient

A 42-year-old woman with eating disorder underwent electroconvulsive therapy (ECT) under general anesthesia with thiamylal 150 mg and suxamethonium 60 mg. On her fourth ECT procedure, premature ventricular contraction (PVC) occurred immediately after the treatment. We speculate that increased release of catecholamine by ECT and hypokalemia caused PVC. It seems that she repeated self-vomiting, because she had hypokalemia, metabolic alkalosis, and weight loss of 3 kg in two weeks before arrhythmia episode. We conclude that in the anesthetic management of patients undergoing ECT a careful attention should be given to body weight change and serum electrolyte care before ECT because it is easy to develop electrolyte abnormality by eating disorder of self-emetic type.     

Changes in the bispectral index during intraabdominal irrigation in patients anesthetized with nitrous oxide and sevoflurane

Surgical stimulation typically results in an activation of electroencephalographic activity. In some instances, painful stimulation in the presence of inadequate anesthesia results in a suppression of the electroencephalogram. This phenomenon has been referred to as a "paradoxical arousal." In our daily practice, we have noted a marked decrease in the bispectral index (BIS) with large delta waves during abdominal surgery when the abdominal cavity was irrigated with normal saline. In the present study, we sought to evaluate changes in BIS during intraabdominal irrigation. Eighteen ASA physical status I-II patients scheduled for elective abdominal surgery were enrolled in the study and allocated randomly to the control group (group C) or the fentanyl group (group F). Anesthesia was induced with 3 mg/kg of thiopental and was maintained with sevoflurane and 50% nitrous oxide. BIS, 95% spectral edge frequency (SEF95), and burst-suppression ratio were recorded using a BIS monitor. Near the end of the procedure, but before irrigation of the abdominal cavity, 1.5 microg/kg fentanyl was given IV to group F. There was no significant change in BIS or SEF95 in group F patients during subsequent irrigation of the abdominal cavity. In contrast, BIS and SEF95 decreased significantly after start of irrigation in group C patients. These data show that the stimulation occurring during intraabdominal irrigation might cause a paradoxical arousal response, as evidenced by a decrease in processed electroencephalographic parameters. Pretreatment with fentanyl suppressed these changes. Anesthesiologists should be aware of this paradoxical arousal response to avoid an inappropriate decrease in the anesthetic concentration in such situations.     

The detection of cerebral hypoperfusion with bispectral index monitoring during general anesthesia

We describe a patient in whom the bispectral index (BIS) decreased to 0 during surgery. A 42-yr-old man with chronic renal failure was scheduled to undergo construction of an arteriovenous shunt. He had a history of acute cerebral hemorrhage. An intracranial hematoma had been removed a month earlier with almost complete neurological recovery. He had uncontrolled hypertension. His systolic blood pressure was 180 mm Hg before anesthesia induction. Anesthesia was induced with 100 mg of propofol and 3% sevoflurane. After laryngeal mask insertion, anesthesia was maintained with nitrous oxide 60% in oxygen and sevoflurane. BIS decreased to near 0 on 2 occasions: after anesthesia induction and shortly after the start of the surgery. His systolic blood pressure decreased to 110 mm Hg and BIS increased when his blood pressure was increased to 130-140 mm Hg. The decrease in BIS was suspected to be the result of decreased cerebral blood flow. The systolic blood pressure of 110 mm Hg (mean blood pressure, 80 mm Hg) was probably less than the lower limit of autoregulation. Although BIS has some limitations as a cerebral monitor, it was useful for detecting possible cerebral hypoperfusion in this case.