Clipping Hind Paws Under Isoflurane Sedation as a Useful Tool for Evaluation of Chronic Pain in CCI Animals.

BACKGROUND: Several behavioral tests have been devised to assess pain in rodent models, one of which is the Chronic constriction injury (CCI) model of the sciatic nerve, including the sensitivity of the paw evaluated through reflex reactions to heat or mechanical stimuli. However, because of their high restless activity and responsiveness to humans, it is tough to give the moving animals consistent stimuli to get consistent and reliable reactions. METHODS: Experiments were performed on male C57BL/6J mice (aged eight weeks) and prairie voles (aged eight weeks). Sham animals (five mice and six prairie voles) and CCI animals (six mice and seven prairie voles) were tested before surgery, four days after, and seven days after surgery. Each animal was rated using a modified rating scale for the scoring of nociceptive behavior. The mechanical threshold test was administered by applying arterial clips to the base of toes under isoflurane-induced sedation. RESULTS: The right hind paw of the CCI administered side showed significant increases in the scores of nociceptive behavior on day 4 and day 7. The right hind paw of the CCI-administered side showed significant reductions in the mechanical threshold test on day 4 and day 7. CONCLUSIONS: The results of the mechanical threshold test were consistent with those of the scoring of nociceptive behavior in CCI model animals, and the method of using arterial clips under sedation was useful for the mechanical threshold test.

Severe Respiratory Event Initially Thought to be Inadvertent Endobronchial Intubation: Possible Complications From Using of a Topical Metered-Dose of 8% Lidocaine Pump Spray.

INTRODUCTION: Pulmonary collapse after intubation is common, and it is caused by a variety of factors. CASE PRESENTATION: A 21-year-old man presented at our operation room to undergo an appendectomy. Except for a history of cigarette smoking, his history was negative. Anesthesia was induced with 100% oxygen and sevoflurane, remifentanil infusion, and propofol. Neuromuscular block was obtained with rocuronium. The tip and cuff of a tracheal tube were lubricated with a topical metered-dose of 8% Lidocaine pump spray. After intubation, SPO2 suddenly decreased. The chest x-ray revealed right upper lobe atelectasis. Fiber optic bronchoscopy showed that a large amount of yellow sticky mucus had been secreted into the right main bronchus. CONCLUSIONS: In Japan, 8% Lidocaine pump spray contains menthol and ethanol as additives. These additives, particularly menthol, might have led to excessive mucus production, although we did not analyze the mucus secretion.

The Lateral Position Improved Airway Patency in Anesthetized Patient With Burn-Induced Cervico-Mento-Sternal Scar Contracture.

A 78-year-old woman with burn-induced cervico-mento-sternal scar contracture was scheduled for laparoscopic cholecystectomy. During inhalational induction of sevoflurane, her airway patency deteriorated. The right lateral position and assist ventilation using a breathing bag dramatically improved her airway patency.

[A case of gastric cancer that responded to a preoperative combination therapy of S-1/CDDP plus trastuzumab].

A 79-year-old man was diagnosed with advanced gastric cancer (cT3, N1, M0, cStage II B) showing regional bulky lymph node metastasis. Invasion of the pancreas and common hepatic artery was suspected. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy (NAC) regimen. After two courses, significant tumor reduction was observed, and the patient underwent distal gastrectomy with D2 dissection. S-1/CDDP plus trastuzumab therapy as NAC for HER2-positive, advanced gastric cancer appears to be an effective treatment.

The effect of the kampo medicine yokukansan on preoperative anxiety and sedation levels.

Background. Preoperative anxiety can lead to unfavorable physiological response such as tachycardia and hypertension. Prevention of preoperative anxiety improves surgical outcome and decreases inpatient stay. Yokukansan is one of prescriptions in Kampo, traditional Japanese herbal medicine, and is known to exert anxiolytic effects. The aim of the present study was to compare the effects of diazepam and Yokukansan on preoperative anxiety, salivary amylase activity, and sedation levels. Methods. Seventy American Society of Anesthesiologists physical status I or II patients presenting for hemicolectomy under general anesthesia combined with epidural anesthesia were enrolled. The Diazepam group received diazepam 5 mg orally and the Yokukansan group received Yokukansan 2.5 g orally. Results. Although levels of anxiety and salivary amylase activity were not different between the two groups, the modified Observer's Assessment of Alertness/Sedation Scale of the Yokukansan group was significantly higher compared to that of the Diazepam group. Conclusion. Yokukansan alleviated preoperative anxiety without undesirable sedation, when compared with diazepam.

Auricular acupuncture at the "shenmen" and "point zero" points induced parasympathetic activation.

Purpose. Since auricular acupuncture is a diagnostic and treatment system based on normalizing the body's dysfunction, auricular acupuncture has been applied for pain relief, relaxation, and so on. These techniques would modulate the autonomic nerve system, thereby inducing the above-mentioned effects. The aim was to see the effect of auricular acupuncture applied to the "Shenmen" and "Point Zero" points on the postoperative heart rate variability (HRV). Methods. Twenty-six patients who underwent hemicolectomy under general anesthesia were randomized into the control or the acupuncture group. After the operation and before emergence, the acupuncture group received auricular acupuncture. An electrocardiographic unit was placed for recording the autonomic nervous activities. Results. The low frequency (LF)/high frequency (HF) ratio of HRV increased (P = 0.0007) in the control, but the ratio in the acupuncture did not change. There were significant differences between the ratios of the two groups at 3 : 00, 4 : 00, and 5 : 00. HF of the acupuncture group tended to be higher. HFs of the acupuncture group were significantly higher than those of the control group at 3 : 00, 4 : 00, and 5 : 00. Conclusion. Auricular acupuncture kept the LF/HF ratio at lower levels and HF at higher levels during postoperative period in the patients who had undergone hemicolectomy.

Transcutaneous Electrical Nerve Stimulation on the PC-5 and PC-6 Points Alleviated Hypotension after Epidural Anaesthesia, Depending on the Stimulus Frequency.

Neuraxial blockade causes arterial hypotension. Transcutaneous electrical nerve stimulation (TENS) at the Neiguan (PC-6) and Jianshi (PC-5) reduces the severity of hypotension after spinal anaesthesia, but did not clarify the optimal stimulus frequency. We hypothesized that the stimulus frequency of TENS at the PC-6 and PC-5 points would influence the severity of hypotension after epidural anaesthesia. 65 ASA I or II male patients presenting for inguinal hernia repair were randomized to five groups: the control group received no treatment; the 2 Hz, 10 Hz, 20 Hz, and 40 Hz groups received TENS at a frequency of 2 Hz, 10 Hz, 20 Hz, and 40 Hz, respectively. The lowest SBP was significantly higher in the 40 Hz group [the control, 84 (74-110) mmHg; the 2 Hz, 96 (62-116) mmHg; the 10 Hz, 100 (68-110) mmHg; the 20 Hz, 96 (64-115) mmHg; the 40 Hz, 104 (75-140) mmHg: P = 0.004]. Significantly less patients experienced hypotension in the 40 Hz group [the control, 78%; the 2 Hz, 43%; the 10 Hz, 38%; the 20 Hz, 38%; the 40 Hz, 8%: P = 0.008]. TENS on the PC-6 and PC-5 points reduced the severity and incidence of hypotension after epidural anaesthesia, depending on the stimulus frequency.

Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via death ligands.

BACKGROUND/AIMS: Phosphatidylcholine reduces chemically-induced hepatocarcinogenesis in rats and the growth of hepatic cancer cells. We planned to determine whether apoptosis pathways via death ligands were induced by phosphatidylcholine. METHODOLOGY: Growth inhibition of hepatic cancer cell lines (HepG2, Hep3B, Alexander, and HuH-7) was examined by MTT assay. On apoptosis induction, flow cytometry analyses were performed after Fas or TNF-alpha ligand stimulation followed by phosphatidylcholine. Expressions of caspase-8, -3 and PARP after phosphatidylcholine stimulation were examined by immunoblotting. TUNEL staining was also performed after phosphatidylcholine stimulation. RESULTS: MTT assays showed growth inhibitions by phosphatidylcholine dose-dependently. Ratios of sub-G1 phase cell population by FACScan significantly increased on 48h phosphatidylcholine stimulation in comparison to the control group (p < 0.05). Fas or TNF-alpha ligand followed by phosphatidylcholine stimulation significantly increased apoptotic cells more than by phosphatidylcholine alone (p < 0.05). Enhanced appearances of cleaved caspase-8, -3 and fragmented PARP were shown on immunoblotting and apoptotic cells on TUNEL staining after phosphatidylcholine stimulation. Phosphatidylcholine was assumed to reduce hepatic carcinogenesis by apoptosis induction via the death ligands (Fas and/or TNF-alpha) pathway followed by caspase-8 and -3 inductions. CONCLUSIONS: Phosphatidylcholine intake may well inhibit carcinogenesis in patients at high risk for hepatocellular carcinoma by apoptosis induction.

The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor.

BACKGROUND/AIMS: Hepatocarcinogenesis is a multifactorial, multistep process that involves the activation of oncogenes or the inactivation of tumor suppressor genes throughout the different stages of hepatocellular carcinoma (HCC) progression. NPRL2 is one of the candidate tumor suppressor genes identified on chromosome 3p21.3, a region which frequently contains genetic abnormalities found in the early stages of the development of various human cancers. In the current study, we aimed to evaluate NPRL2 expression in HCC and to explore the prognostic significance of NPRL2. METHOD: We investigated NPRL2 mRNA expression in 70 HCC specimens, using quantitative real-time reverse transcription polymerase chain reaction analysis, and the correlation between NPRL2 expression and clinicopathologic parameters. RESULTS: NPRL2 mRNA was found to be expressed equally in both HCC tissues and corresponding non-cancerous liver tissues. However, higher NPRL2 expression correlated significantly with tumor size (P = 0.0062) and serum PIVKA-II levels (P = 0.0002). Univariate and multivariate analyses revealed that higher NPRL2 mRNA expression was an independent prognostic factor for overall survival (risk ratio 0.39; P < 0.0001). CONCLUSION: Our results suggest that NPRL2 mRNA expression has prognostic significance for the survival of patients with HCC.

Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments.

BACKGROUND/AIMS: We examined whether phosphatidylcholine inhibited growth of hepatic cancer, as previously shown for menaquinone-4 (vitamin K2). METHODS: Growth inhibitions by phosphatidylcholine and/or menaquinone-4 and apoptosis induction by phosphatidylcholine were evaluated in vitro using human hepatic cancer cell lines (Hep-3B, Hep-G2, HuH-7, and Alexander). Effects of these agents were then investigated in male Sprague-Dawley rats against hepatocarcinogenesis induced by diethylnitrosamine plus phenobarbital. All rats were killed to examine livers to evaluate inhibitory potential macroscopically and immunohistochemically using an antibody against the marker of carcinogenesis, glutathione S-transferase and apoptotic induction by phosphatidylcholine using TUNEL staining. Blood samples were obtained by cardiac puncture. RESULTS: In vitro, phosphatidylcholine and menaquinone-4 each inhibited cancer cell growth and phosphatidylcholine induced apoptosis dose-dependently. Moreover, exposure to both synergistically inhibited growth in Hep-3B. In vivo, diets containing phosphatidylcholine with or without menaquinone-4 significantly reduced the number of macroscopic hepatic tumor nodules and the extent of abnormally immunoreactive foci conserving hepatic function on serum examinations compared with controls given only the carcinogens. Moreover, phosphatidylcholine supplementation induced apoptosis on TUNEL staining of liver sections. CONCLUSIONS: Given together, phosphatidylcholine and menaquinone-4 may exhibit synergy against hepatocarcinogenesis conserving hepatic function that could benefit patients at high risk for hepatocellular carcinoma.

Gene therapy for hepatocellular carcinoma using sonoporation enhanced by contrast agents.

We examined whether sonoporation enhanced by a contrast agent (BR14) was effective in gene therapy for hepatocelluar carcinoma (HCC). Human hepatic cancer cells (SK-Hep1) and plasmid cDNAs expressing green fluorescent protein (GFP), interferonbeta (IFNbeta), and LacZ were used. In vitro, SK-Hep1 cell suspensions with DNA and BR14 were sonoporated. Expressions of every plasmid cDNA and the antitumor effect of IFNbeta were analyzed. In vivo, GFP and IFNbeta genes with BR14 were directly injected into subcutaneous tumors using SK-Hep1 in nude mice, and transcutaneous sonoporation of the tumors was performed. GFP gene transfections and tumor diameters after IFNbeta gene transfection were examined. In vitro, no SK-Hep1 cells were transfected without sonication, whereas transfections were successful after sonication with BR14. Antitumor effect of IFNbeta gene transfection by ultrasound (US) and with BR14 was revealed. In vivo, the SK-Hep1 cells expressed GFP, and the IFNbeta gene transfection by US with BR14 reduced tumor size significantly. In conclusion, gene therapy with sonoporation enhanced by a contrast agent may become a new treatment option for HCC.

Factors in successful radiofrequency ablation therapy for malignant liver tumors.

BACKGROUND/AIMS: Radiofrequency ablation has become a new therapeutic method for treating malignant liver tumors. We reviewed our experience to identify the factors involved in successful radiofrequency ablation therapy. METHODOLOGY: Patients who underwent this therapy between 1999 July and 2002 July were reviewed for the characteristics of their tumors, clinical data and operative techniques used. RESULTS: Sixty-one patients (hepatocellular carcinoma 50 and metastatic tumors 11) were ablated. Forty-six cases (75.4%) were ablated effectively. Survival of patients with hepatocellular carcinoma was superior to those with metastases. The effective factor was the number of nodules while the survival factors were the number of nodules and the maximum tumor diameter. Recurrence factors in patients with hepatocellular carcinoma ablated effectively were poor hepatic function due to cirrhosis and higher protein induced by vitamin K absence or antagonist-II (PIVKA-II). CONCLUSIONS: The survival of patients with hepatocellular carcinoma was significantly better than those with metastases. We recommend radiofrequency ablation therapy for cases having a single hepatic tumor less than 3.5 cm in diameter (4 cm for hepatocellular carcinoma requiring much care). In patients with hepatocellular carcinoma, hepatic function with cirrhosis and PIVKA-II showed a significant correlation with recurrence.

Emergency pylorus-preserving pancreatoduodenectomy followed by second-stage pancreatojejunostomy for a gastrointestinal stromal tumor of the duodenum with an intratumoral gas figure: report of a case.

We report a case of a duodenal gastrointestinal stromal tumor (GIST) necessitating urgent surgery because of a gas figure on computed tomography (CT). A 46-year-old woman, complaining chiefly of upper abdominal pain and tarry stools, consulted a local doctor. A gastrointestinal fiberscopy revealed an ulcer in the second part of the duodenum, and the patient was admitted to our hospital where a dynamic CT scan showed a hypervascular solid tumor in the pancreatic head. A repeat CT scan done 4 days later showed a gas figure in the tumor, necessitating an emergency pylorus-preserving pancreatoduodenectomy (PpPD). First, we performed a tube pancreatostomy for complete external drainage of the pancreatic juice, and planned a second-stage pancreatojejunostomy for the near future. Histopathologically, the tumor was diagnosed as a GIST originating in the duodenum. The patient was discharged on postoperative day 23 after an uneventful postoperative recovery. Her local doctor completed the second-stage pancreatojejunostomy.