Pulmonary thromboembolism in lung surgery: use of unfractionated heparin.

BACKGROUND: While thoracic surgeons occasionally encounter pulmonary thromboembolism, the use of unfractionated heparin may cause adverse effects. METHODS: We assessed a series of 323 consecutive pulmonary operations performed during 4 years from 2008 to 2011. All patients were given elastic stockings and intermittent pneumatic compression. During the first 2 years (2008-2009), none of the 169 patients received unfractionated heparin. In the second 2-year period (2010-2011), 135/154 patients received subcutaneous unfractionated heparin, either 5000 units (n = 37) or 2500 units (n = 93) twice daily for 3 days, or continuous intravenous unfractionated heparin (n = 5). The epidural catheters were withdrawn 6 h or more after unfractionated heparin use. Among patients without postoperative unfractionated heparin, 8 (42.1%) had a bleeding risk and 5 (26.3%) had limited operative time. RESULTS: One (0.6%) patient developed pulmonary thromboembolism during 2008-2009, but none had this complication during 2010-2011. The adverse outcome of intrathoracic bleeding occurred in one (2.7%) of the patients given 5000 units of unfractionated heparin, but no epidural hematomas occurred in these patients. CONCLUSION: Patients undergoing thoracic surgery at low risk of bleeding may receive unfractionated heparin to prevent pulmonary thromboembolism while avoiding epidural complications.

Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys.

A block/homo-mixed polyplex micelle, comprising of cationic homo polymer: poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} P[Asp(DET)] and block copolymer: polyethylene glycol (PEG)-b-P[Asp(DET)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration. In the present study, we investigated the potential of immunogene therapy by intraperitoneal (i.p.) administration of block/homo polyplex micelles for peritoneal dissemination. For evaluation of transgene expression in vivo, block/homo polyplex micelles showed 12-fold higher level in luciferase expression evaluated by bioluminescence imaging system at 24 h after the i.p. administration compared with block polyplex micelles composed with only PEG-b-P[Asp(DET)] in nude mice bearing peritoneal dissemination. The distribution of block/homo polyplex micelles and intracellular uptake of pDNA was observed in tumor nodules. The tumor growth and the prolonged survival rate for the mice harboring disseminated pancreatic cancer more significantly compared with the mock. The antitumor effect of GM-CSF gene therapy was mediated via the activation of natural killer cells. For safety evaluation, block/homo polyplex micelles indicated almost no adverse events for patho-physical findings and blood examinations in mice and cynomolgus monkeys, although slight increases in serum fibrinogen were observed in the monkey model. In conclusion, block/homo polyplex micelle-based immunogene therapy via i.p. administration may be a safe and effective approach for suppressing intractable peritoneal dissemination.

Does antimicrobial homogeneity index influence surgical site infection? A 10-year study in lung, breast, and general surgery.

To address whether hospital antimicrobial use influences surgical site infection (SSI), we investigated factors including antimicrobial homogeneity index (AHI), an indicator of prescription diversity, with a retrospective study during 120 months for patients undergoing lung, breast, and general surgery (n = 4,510). We analyzed the odds ratios of background factors for SSI and the correlation between AHI and drug susceptibility in isolates of SSI. A total of 243 cases of SSI (5.4%) occurred. Factors that significantly contributed for SSI were operative time [odds ratio (OR), 1.78; 95% confidence interval (CI), 1.33-2.39; P < 0.001], American Society of Anesthesiologists' score (OR, 1.68, 95% CI, 1.23-2.28; P < 0.001), endoscopic use (OR, 0.10, 95% CI, 0.04-0.24; P < 0.001), lung and breast surgery versus general surgery (OR, 0.12, 95% CI, 0.06-0.22; P < 0.001), increased AHI (OR, 0.72, 95% CI, 0.55-0.95; P = 0.020), and older age (OR, 2.08, 95% CI, 1.39-3.11; P < 0.001). AHI showed a positive correlation coefficient (CC, P < 0.05) with susceptibility to ampicillin (CC = +0.327), cefotaxime (CC = +0.142), imipenem/cilastatin (CC = +0.101), and sulbactam/cefoperazone (CC = +0.145). AHI, which has been described to help prevent drug resistance, was associated with increased susceptibility in microbes of SSI. This finding in part may explain that increase in AHI reduced SSI.

Perioperative antimicrobials in chest surgery patients positive for methicillin-resistant Staphylococcus aureus.

In pulmonary surgery, methicillin-resistant Staphylococcus aureus (MRSA)-positive patients present an issue of perioperative antimicrobials. During 1996 to 2009 in a total of 1,080 pulmonary operations, MRSA was detected before 20 operations. Perioperatively, we followed the Sanford Guide using vancomycin (VCM) or arbekacin (ABK) in MRSA-positive cases at high risk (n = 14), including 1 with clinical infection and 13 with colonization. We used 1-day cefazolin (CEZ) in MRSApositive cases at low risk (n = 6). We defined the outcome as surgical site infection (SSI) that included death from infection. The 14 high-risk cases received a median of 3 days of VCM or ABK, of which 1 (7%) developed SSI. Of the cases given CEZ, we noted SSI in 1 of 6 low-risk cases (17%). Thus, MRSA-positive pulmonary surgery patients at large may receive 3-day VCM or ABK.

Preventing a pitfall: no-knife staplers that require caution during handling.

For safer division of the pulmonary vessels at video-assisted thoracoscopic surgery (VATS), a no-knife stapler (NAW ENDOPATH Flex45 No Knife Endoscopic Linear Stapler, Ethicon Endo-Surgery) is of help. We have used it during 177 sessions in 156 patients and noted two incidences where several of the staples were malformed but did not cause a bleeding event. A close investigation revealed that the cause was excessive rotation of the articulation lever. Thus, to avoid staple malformation, the articulation lever should not be rotated beyond its limit of mobility.

[Chemotherapy for non-small cell lung cancer: split-dose administration of Cisplatin over four consecutive days and Vinorelbine ditartrate].

PURPOSE: At present, combination chemotherapy with Cisplatin (CDDP) and Vinorelbine ditartrate (VNR) is one of the standard regimens for non-small cell lung cancer (NSLC). To avoid renal damage by CDDP, hydration and diuretic are indicated. But elderly/postoperative patients who have reduced lung vessel capacity are a high-risk group for pulmonary edema/right heart failure by hydration. In our hospital, CDDP is administered on four consecutive days without large hydration. MATERIAL & METHODS: CDDP: 80 mg/m2 (over four consecutive days)without large hydration+VNR: 20 mg/m2 was administered 30 NSLC patients(Stage III A & IV). Serum concentration of CDDP was monitored. RESULT: Response rate was CR: 0 case; PR: 9 cases; SD: 16 cases; PD: 5 cases. Mean survival time (MST) was 292 days. The efficacy and prognosis are equivalent to a conventional CDDP+VNR regimen. On the other hand, side effects were reduced; neutrocytopenia (> Grade 3): 17%, renal dysfunction (>Grade 1): 17%. Mean serum concentrations of CDDP were accumulated day by day, 0.91 microg/mL(Day 1), 2.44 microg/mL(Day 4), but were all under the toxic threshold(8 microg/mL). CONCLUSION: Our regimen (CDDP given over four consecutive days without large hydration) may become a regimen for the high-risk patient.

SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigens and has a significant genetic component. Antisense RNA transcripts have been implicated in gene regulation. Here we have identified a novel zinc-finger gene, designated ZFAT (zinc-finger gene in AITD susceptibility region), as one of the susceptibility genes in 8q23-q24 through an initial association analysis using the probands in the previous linkage analysis and a subsequent association analysis of the samples from a total of 515 affected individuals and 526 controls. The T allele of the single-nucleotide polymorphism (SNP), Ex9b-SNP10 located in the intron 9 of ZFAT, is associated with increased risk for AITD (dominant model: odds ratio = 1.7, P = 0.000091). The Ex9b-SNP10 falls into the 3'-UTR of truncated-ZFAT (TR-ZFAT) and the promoter region of the small antisense transcript of ZFAT (SAS-ZFAT). In peripheral blood lymphocytes, SAS-ZFAT is exclusively expressed in CD19+ B cells and expression levels of SAS-ZFAT and TR-ZFAT seemed to correlate with the Ex9b-SNP10-T-associated ZFAT-allele, inversely and positively, respectively. The Ex9b-SNP10 is critically involved in the regulation of SAS-ZFAT expression in vitro and this expression results in a decreased expression of TR-ZFAT. These results suggested that the SNP-associated ZFAT-allele plays a critical role in B cell function by affecting the expression level of TR-ZFAT through regulating SAS-ZFAT expression and that this novel regulatory mechanism of SNPs might be involved in controlling susceptibility or resistance to human disease.

Association of the T-cell regulatory gene CTLA4 with Graves' disease and autoimmune thyroid disease in the Japanese.

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigen. The cytotoxic T-lymphocyte antigen-4 ( CTLA4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3'UTR of the CTLA4 gene, in which the three single-nucleotide polymorphisms (SNPs) CT60, JO31, and JO30 were strongly associated with AITD. In order to determine the association of the CTLA4 gene with AITD in the Japanese, case-control association analysis for the four SNPs of the CTLA4 gene using 380 AITD patients and 266 healthy controls was done. Among the SNPs examined, the SNP JO31 was most significantly associated with AITD in the Japanese, whereas the association of the JO30 with AITD was not observed. The frequency of the disease-susceptible G allele of the JO31 of the Japanese control was higher than that of the Caucasians (67.1% vs 50.2%); however, the G allele of the JO31 was associated with Graves' disease (GD) (67.1% vs 76.3%, P=0.0013) and AITD in the Japanese (67.1% vs 74.2%, P=0.0055). Furthermore, the G allele of the JO31 was associated with the increased risk for GD [ P=0.0051, odds ratio (OR)=1.7] and AITD ( P=0.016, OR=1.5) in a dominant model. These results suggested that the CTLA4 gene is involved in the susceptibility for GD and AITD in the Japanese.