Intraoperative complications of thoracoscopic surgery for mediastinal tumors

We report intraoperative complications of thoracoscopic surgery for mediastinal tumors. Forty cases of mediastinal tumor were undergone thoracoscopic surgery at the hospital from 1999 to 2002. The patient's ages ranged from 18 to 74 years old with a mean of 47.7. Location of these tumors were anteriormediastinal in 20 cases, middlemediastinal in 6 cases, posteriormediastinal in 11 cases, and superiormediastinal in 3 cases. Intraoperative complications were rupture of the cyst in 9 cases, bleeding over 150 ml in 5 cases, injury of lung caused by adhesiolysis in 5 cases, and injury of nerve in 3 cases. The mean operation time was 103.8 minutes. Postoperative hospital stay ranged from 2 to 22 days with a mean of 5.9 days. All are alive with no recurrences or postoperative complications.     

Co-cultivation of pancreatic cancer cells with orthotopic tumor-derived fibroblasts: fibroblasts stimulate tumor cell invasion via HGF secretion whereas cancer cells exert a minor regulative effect on fibroblasts HGF production

The intensive stromal reaction is one of characteristics of pancreatic exocrine carcinoma. The mutual interaction between pancreatic cancer cells and orthotopic tumor-derived fibroblasts have not been clarified yet. In this study, we sought to elucidate the mechanism underlying the tumor-stromal interaction with an in vitro coculture experimental system. Considerable strong c-Met expression was detected in seven out ten lines of human pancreatic carcinoma cells, as determined by Western blotting. For hepatocyte growth factor (HGF)-production, however, none or only trace amounts of HGF could be detected in those ten cell lines. Of the two lots of tumor-derived fibroblasts obtained from two pancreatic cancer patients, the fibroblasts capable to produce HGF could initiate an apparent invasion-stimulating response in strong c-Met-expressed Suit-2 and Panc-1 cells but not in faint expressed Mia PaCa-2 and BxPC-3 cells. A specialized HGF antagonist, NK4 would effectively inhibit the fibroblast-mediated invasive growth, thus proving the key role of the paracrine-fashioned HGF/c-Met pathway in the tumor-stromal interaction. On the other hand, the regulative action of cancer cells on HGF expression of fibroblasts was also investigated using direct or indirect coculture systems. For the fibroblasts that originally did not produce HGF, cancer cells failed to show any HGF-inductive effect. For the HGF-producing fibroblasts, despite of somewhat upregulation or downregulation in fibroblast HGF expression, the feedback regulation by studied pancreatic cancer cells in both coculture modes were relatively limited. This in vitro study sketched out the interaction between cancerous and stromal compartments with an emphasis on HGF/c-Met signal pathway, thus possibly helping to unveil the more complicated mutual modulation in vivo between pancreatic cancer and host mesenchymal tissues.     

The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer

BACKGROUND: Combination chemotherapy of methotrexate, actinomycin D and cisplatin (MAP) is reported to be effective against gestational choriocarcinoma. METHODS: Eight patients with metastatic testicular cancer who had elevated beta-hCG were treated with MAP. They included three refractory cases and two relapsed cases. An additional three patients received MAP as part of the induction therapy. The MAP therapy consisted of methotrexate (10 mg/m2) on days 1-5, actinomycin D (0.01 mg/kg) on days 1-5 and cisplatin (70 mg/m2) on day 1. RESULTS: In all three refractory patients, MAP failed to achieve tumor marker normalization. However, the elevated tumor markers normalized after MAP in the two cases of relapse. Of these two, one patient relapsed again 7 months after MAP and was subsequently salvaged with high-dose chemotherapy. The other patient relapsed and died of the disease 30 months after receiving MAP. Of the three patients who received MAP as part of the induction chemotherapy, one with pure choriocarcinoma achieved tumor marker normalization after MAP and is still alive without disease progression. In the other two patients, MAP failed to achieve marker normalization and the patients received high-dose chemotherapy. The toxicities were mainly bone marrow suppression and mucositis, which were almost acceptable. CONCLUSIONS: The results demonstrated the limited efficacy of MAP as salvage therapy. In addition, the efficacy of MAP as part of induction chemotherapy was negligible. However, there might be some role for MAP as a salvage therapy for patients with pure choriocarcinoma.     

Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig model of experimental allergic rhinitis

TAK-427 (2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist.     

Independent action of serine/threonine protein phosphatase in ovarian cancer plasma membrane and cytosol during gonadotropin-releasing hormone stimulation

Reversible serine/threonine protein phosphorylation catalyzed by kinases and phosphatases 2A (PP2A) plays a crucial role in cellular growth and differentiation. We attempted to determine the subcellular location of PP2A in ovarian cancer cells and its regulation by gonadotropin-releasing hormone (GnRH), which is known to have anti-proliferative actions on ovarian cancers. Surgically removed ovarian cancers were screened for GnRH receptor expression prior to subcellular fractionations. PP2A activity was assessed by measuring the dephosphorylation of phosphopeptide highly selective for the PP2A in cytosol and membranes fractionated on a continuous sucrose density gradient. To assess GnRH effects, cloned cell lines were pretreated with or without a GnRH agonist. There were three peaks of PP2A activity, corresponding by marker enzyme analysis to the cytoplasm, plasma membrane and endoplasmic reticulum fractions. The kinetic analysis showed a different activity in cytosol and membrane; Km values for substrate of 185 microM and Vmax of 555 pmol/mg protein/30 min for cytosol, and 28 microM and 83 pmol/mg protein/30 min for plasma membrane, respectively. PP2A-specific inhibitor okadaic acid inhibited the cytosolic and membrane-associated activity by 50% when added at 2 nM and 50 nM (p<0.001). A 50% inhibitory effect of NaF was obtained at 0.5-1 mM for cytosol and 5 mM for membranes (p<0.001). In Caov-3 cells exposed GnRH, PP2A activity of plasma membrane increased by 1.3-fold (p<0.001) but that of cytosol was not affected. PP2A activity in the plasma membrane of ovarian cancer cells might be distinct from that present in the cytosol. The plasma membrane PP2A may be responsible for a portion of an increased ser/thr protein phosphorylation-dephosphorylation turnover that occurs during cell exposure to GnRH.     

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection

Background In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT).Methods The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group).Results Among the 156 patients, who were monitored for 11–26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P 0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0U/ml for NMP22 and 6.0ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively.Conclusions Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.     

Association between diabetes mellitus and hepatocellular carcinoma: results of a hospital- and community-based case-control study

The present study was performed to investigate the relationship between diabetes mellitus (DM) and primary hepatocellular carcinoma (HCC). Incident HCC cases were recruited in Kyushu, Japan. Ethnicity-, age-, gender-, residence-matched hospital controls and community controls were collected. Information on viral hepatitis B (HBsAg) or viral hepatitis C infection, history of blood transfusion, past histories including DM, amount of drinking or smoking, and genotypes of alcohol metabolizing enzymes was collected. Associations between these items and HCC were analyzed multivariately by conditional logistic regression analysis. Two hundred and twenty two (177 males and 45 females) case-control sets were completed between July 1995 and June 2000. Since hospital controls turned out to be a biased one or those sampled from a DM-prone population, a multivariate analysis was performed for the HCC-community controls sets, and it yielded significantly elevated odds ratio (OR)s due to past histories of DM (2.522; 95% Confidence Interval (CI) = 1.267-5.020), blood transfusion (1.747; 1.136-2.689), and unit increment of alcohol consumption (1.358; 1.096-1.684) for males. The same analyses of the HCC-community-controls sets for females, revealed an elevated but not statistically significant OR due to past histories of DM (4.195; 0.808-21.805). A multivariate analysis revealed that DM might be a risk factor for HCC.     

Efficacy of a detector tube method in formaldehyde measurement

In order to determine the efficacy of a detector tube method in formaldehyde (HCHO) measurement, we performed a chamber experiment and a field study. The experiment clearly showed that the value obtained by the detector tube method was significantly correlated to that obtained using an active-DNPH method, and was not influenced by the coexistence of toluene, xylene or carbon monoxide, but was by acetaldehyde. In the field study, we investigated 171 rooms in 81 houses. Indoor air was simultaneously sampled for 30 minutes by both an active-DNPH method and the detector tube method. The mean HCHO concentration in the 171 rooms was 0.110 +/- 0.089 ppm determined by the active-DNPH method and 0.12 +/- 0.10 ppm by the detector tube method. Regression analysis showed that the two measures closely correlated with a regression equation Y=1.057 X + 0.002 (r=0.912, p<0.0001), where X is the HCHO concentration determined by the active-DNPH method and Y is that determined by the detector tube method. The mean acetaldehyde concentration in the 171 rooms was 0.024 +/- 0.018 ppm using the active-DNPH method, and no correlation was found between acetaldehyde concentrations using the active-DNPH method and the values obtained by the detector tube method. Therefore, this study clearly showed that the detector tube method is not only simple and fast but also precise in measuring HCHO in indoor air.     

Two autopsy cases with Pelizaeus-Merzbacher disease phenotype of adult onset, without mutation of proteolipid protein gene

We report the autopsy cases of two brothers which are pathologically compatible with Pelizaeus-Merzbacher disease (PMD). Both patients had a late onset (at the ages of 29 and 42 years) and chronic neurological symptoms including tremor, ataxia and dementia. The T2-weighted magnetic resonance imaging of the younger brother demonstrated increased signal areas with sparing of small areas in the cerebral white matter. The postmortem examinations, obtained at the ages of 45 and 61 years, showed similar neuropathological findings. Histologically, a cardinal finding was a lack of myelin in large parts of white matter with the preservation of islands of intact myelin, resulting in a “tigroid” appearance. Only small amounts of sudanophilic material were present. The axons were relatively well preserved, but oligodendrocytes were numerically reduced. Ultrastructurally, myelin sheaths in the white matter were markedly thin. Immunohistochemistry showed that proteolipid protein (PLP) was reduced in the affected white matter. However, genetic studies did not reveal exonic mutations or duplications of the PLP gene. We conclude that the two cases are a rare type of dysmyelinating disorder with PMD phenotype of adult onset and could be caused by previously unrecognized abnormalities of the PLP gene or other genes. Received: 28 September 1998 / Revised: 25 January 1999, 12 April 1999 / Accepted: 12 April 1999