Influenza pandemic preparedness and severity assessment of pandemic (H1N1) 2009 in South-east Asia.

Pandemic (H1N1) 2009 poses a serious global health threat. However, the global impact of this new pandemic remains uncertain. Past pandemics had different impacts on mortality which varied between countries. Several countries in South-east Asia have already developed their national pandemic preparedness plans. However, these plans have focused on surveillance for and response to the highly pathogenic avian influenza (H5N1), including the rapid containment of H5N1. The newly emerged pandemic (H1N1) 2009 is different from H5N1 in terms of severity and requires different approaches. There are several factors that can potentially affect the severity of pandemic (H1N1) 2009, including a population's vulnerability and response capacity. The pattern of severity appears to be changing with the spread of pandemic (H1N1) 2009, which can be conceptualized in a step-wise manner based on observation of the current situation. The overall impact of pandemic (H1N1) 2009 remains unknown and it is difficult to assess its severity. However, there is an urgent need to assess its potential severity based on the available data so that appropriate responses can be provided in order to mitigate its impact.

Outbreak of measles and rubella in refugee transit camps.

In 2004, concurrent measles and rubella outbreaks occurred in four camps hosting 2767 Liberian refugees in Côte d'Ivoire. Sixty rash and fever cases were identified. From 19 January to 23 February 2004 (weeks 8-13), measles IgM testing showed that 61.1% were positive. The highest incidence rate (18.5%) of measles was observed in children aged <9 months. Ninety-three percent of children aged between 6 months and 15 years received a measles vaccine during week 13, but the rash and fever cases continued to occur. This prompted a systematic test for both measles and rubella IgM antibodies. Rubella IgM testing revealed 74.0% positive cases between 14 February and 25 April (weeks 11-21). The highest incidence rate (3.88%) of rubella was found in children aged between 5 and 15 years. Supplemental immunization with a measles-mumps-rubella (MMR) vaccine was conducted during week 20. This study illustrates the importance of testing for both measles and rubella in outbreaks of rash and fever in refugee settings.

Extensive first-principles molecular dynamics study on Li encapsulation into C60 and its experimental confirmation.

The aim of increasing the production ratio of endohedral C60 by impinging foreign atoms against C60 is a crucial matter of the science and technology employed towards industrialization of these functional building block materials. Among these endohedral fullerenes, Li+@C60 exhibits a wide variety of physical and chemical phenomena and has the potential to be applicable in areas spanning the medical field to photovoltaics. However, currently, Li+@C60 can be experimentally produced with only ∼1% ratio using the plasma shower method with a 30 eV kinetic energy provided to the impinging Li+ ion. From extensive first-principles molecular dynamics simulations, it is found that the maximum production ratio of Li+@C60 per hit is increased to about 5.1% (5.3%) when a Li+ ion impinges vertically on a six-membered ring of C60 with 30 eV (40 eV) kinetic energy, although many C60 molecules are damaged during this collision. On the contrary, when it impinges vertically on a six-membered ring with 10 eV kinetic energy, the production ratio remains at 1.3%, but the C60 molecules are not damaged at all. On the other hand, when the C60 is randomly oriented, the production ratio reduces to about 3.7 ± 0.5%, 3.3 ± 0.5%, and 0.2 ± 0.03% for 30 eV, 40 eV, and 10 eV kinetic energy, respectively. Based on these observations we demonstrate the possibility of increasing the production ratio by fixing six-membered rings atop C60 using the Cu(111) substrate or UV light irradiation. In order to assess the ideal experimental production ratio, the 7Li solid NMR spectroscopy measurement is also performed for the multilayer randomly oriented C60 sample irradiated by Li+ using the plasma shower method combined with inductively coupled plasma atomic emission spectroscopy (ICP-AES). Time-of-flight mass spectroscopy measurements are also performed to cross check whether Li+@C60 molecules are produced in the sample. The resulting experimental estimate, 4% for 30 eV incident kinetic energy, fully agrees with our simulation results mentioned above, suggesting the consistency and accuracy of our simulations and experiments.

Evaluation of the mechanical strength and patency of functional end-to-end anastomoses.

BACKGROUND: Although many mechanical devices are being developed for functional end-to-end anastomosis (FETEA), the best choice remains to be determined. The mechanical strength of each device is an important factor associated with anastomotic leakage. In turn, anastomotic patency is related to postoperative stenosis. This study examined the bursting pressure and circumference of several FETEAs. METHODS: Young domestic pigs were used in this study. In experiment 1, a 10-cm segment of intestine was transected using an EndoGIA 60 blue, EndoGIA 60 green, or GIA 60 blue stapler, and the bursting pressure of each instrument's mechanical staple line was examined. In experiment 2, after FETEA had been created with EndoGIA 60 blue, the bursting sites were examined, and the bursting pressures of buttressed and nonbuttressed FETEA were measured and compared. In experiment 3, the circumference of FETEA was compared between the closed technique and reinforcement. RESULTS: The bursting pressure of EndoGIA 60 blue was significantly higher than that of the other devices. When an anastomotic crotch was buttressed, the bursting pressure (44 +/- 13 mmHg) was significantly increased over that of the nonbuttressed FETEA (27.5 +/- 5.8 mmHg; p < 0.05). The circumference of FETEA using the wide technique (92.7 +/- 2.3 mm) was larger than that using the offset technique (55.7 +/- 5.8 mm). CONCLUSIONS: The bursting pressure of the mechanical staple line using the EndoGIA 60 stapler was the strongest. Functional end-to-end anastomosis was stronger when created with buttress of an anastomotic crotch, and larger circumferences were created with the wide technique.

Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

We investigated the effect of stabilized Fab oligomerization by disuccinimidyl suberate on tumor uptake in a pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A10, which was previously shown to react specifically with gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in tumors than Fab or F(ab')2 but lower than IgG. However, oligomers with C-C bonds maintained higher tumor to normal tissue specificity ratios than IgG 24 h post-infusion. In conclusion, tumor uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab')2, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose radionuclides with reduced radio-uptakes in normal tissues for the radioimmunotherapy of gastrointestinal carcinomas.

Organ preferential metastasis related to tissue- and serum-selective growth or migration properties of hamster pancreatic carcinoma cells.

We have investigated tissue- and serum-selective growth or migration activities of two hamster pancreatic carcinoma cell lines, KH-PC and HapT1. In experimental metastatic models, multiple liver metastases were observed for hamsters injected with KH-PC cells, while HapT1 had little tendency to metastasize to the liver. Micrometastases in the lung were observed for both KH-PC and HapT1. Liver extract inhibited the growth of HapT1 cells when compared to a 1% bovine serum albumin control, while KH-PC growth was not inhibited by liver extract. Liver extract showed chemoattractive activity to KH-PC but not to HapT1 cells. No notable differences were shown in either chemoattractive or growth properties of lung extract toward either cell line. These activities of lung extracts were weaker than those of liver extract to KH-PC. Hamster portal vein serum (PVS) had higher mitogenic activity toward both KH-PC and HapT1 cells, compared with serum derived from the vena cava (VS). Chemokinetic activity of PVS or VS toward KH-PC was slightly higher than that toward HapT1. In a chemoinvasion assay with liver extract and PVS, a 6-fold greater number of invasive cells was observed for KH-PC cells when compared to HapT1 cells. In a chemoinvasion assay with lung extract and VS, there was no difference between the cell lines. Our results suggest that complex activities of tissue- and serum-selective growth or migration were related to organ preferential metastasis of these hamster pancreatic carcinoma cell lines.

Optimal duration of oral adjuvant chemotherapy with Carmofur in the colorectal cancer patients: the Kansai Carmofur Study Group trial III.

A multi-institutional study was performed to evaluate the appropriate duration of oral administration of Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative operation. Patients were divided into two: i) short duration group receiving 6 months of HCFU administration and ii) long duration group receiving 1 year of the administration, using a centralized registration system. Among 364 patients entered in this study, 293 evaluable cases were analyzed to investigate the appropriate duration of adjuvant oral chemotherapy. No statistical differences were found in the cumulative 5-year disease-free or survival rates between the groups. However, the actual duration of oral HCFU administration differed in the patients of short and long duration groups from the protocol. Namely, more than 70% of the patients received a different duration of oral adjuvant chemotherapy in each of the groups. Therefore, apart from this division of two groups, correlation between the actual duration of oral HCFU administration and the prognosis was examined in these patients. As a result, it was suggested that oral adjuvant chemotherapy with HCFU would be effective in colon cancer patients when the duration of administration exceeded 330 days. In rectal cancer patients, however, adjuvant chemotherapy with HCFU alone was considered to be not sufficient to affect the prognosis.

Proliferating cell nuclear antigen as a predictor of therapeutic effect of continuous 5-fluorouracil administration in gastric cancer.

The change of proliferating cell nuclear antigen (PCNA) expression was examined in three gastric cancer cell lines, MKN28, MKN45 and MKN74, during continuous or bolus exposure to 5-fluorouracil (5-FU). The cytotoxic effect of 5-FU was almost the same in all the cells. PCNA expression was higher at 24 and 72 h after continuous 5-FU treatment than before treatment. Continuous 5-FU treatment of cells revealed higher expression of PCNA protein and mRNA than did bolus treatment. Flow cytometry revealed that 5-FU increased cell population at the late G1 or S phase 24 and 72 h after treatment. PCNA values at the late G1 and S phase were significantly higher than those at other phases 24 h after treatment. These results suggest that PCNA expression increased due to cell cycle accumulation at late G1 and S phases. Thus PCNA values just after chemotherapy of gastric cancer may be useful in predicting the therapeutic effects of continuous 5-FU administration.

Radiolocalization of pancreatic carcinoma xenografts in nude mice with radiolabeled chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody A10.

Recombinant mouse-human chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody (MAb) A10 react with various GI carcinomas. We tested radiolocalization of pancreatic carcinoma xenografts in nude mice using radiolabeled chimeric A10 Fab fragments, comparing them with murine Fab fragments and parental MAb. For mice injected with chimeric A10 Fab fragments, we obtained significantly higher uptake in tumors than in normal tissues at 24 and 48 h after injection. In addition, tumor/normal tissues labeling ratios for chimeric A10 Fab fragment were significantly greater than those for murine MAb at 24 h postinfusion. However, no significant difference in biodistribution was observed between chimeric and murine Fab fragments. In autoradiography imaging studies, we obtained clearer tumor detection without visible uptake in normal organs for chimeric Fab fragments than for murine MAb. These results suggest that chimeric Fab fragments of A10 could be a potentially useful candidate for radioimmunodetection of pancreatic carcinomas.

Expression of thymidylate synthase in cancer of the ampulla of Vater.

The clinical and therapeutic significance of thymidylate synthase (TS) in cancers of the ampulla of Vater have not yet been reported. We immunohistochemically evaluated TS expression in 33 ampullary cancers using an anti-TS antibody. TS expression, clinicopathologic variables, and survival rates were examined and the correlations between these parameters were identified. Fifteen patients were found to express high levels of TS (high TS group), while 18 patients expressed low levels of TS (low TS group). No significant difference was found between TS expression and clinicopathologic factors. Univariate and multivariate analysis revealed that lymph node metastasis and pancreatic invasion are important variables for independently predicting post-operative survival. Although TS expression was not identified as an important factor for postoperative survival, recurrent cases in patients with chemotherapy existed only in the high TS group. In the present study, it was found that TS expression itself in cancers of the ampulla of Vater has no impact in predicting the prognosis of ampullary cancers, but a chemotherapeutic benefit of evaluating TS expression may exist.

Evaluation of gastroenteric bypass for unresectable pancreatic cancer.

BACKGROUND/AIMS: It is controversial as to whether gastroenteric bypass is helpful for patients with unresectable pancreatic cancer. This study was designed to evaluate the effects of gastroenteric bypass on dietary intake and the symptoms of gastric outlet obstruction in these patients. METHODOLOGY: We reviewed the cases of 101 patients with unresectable pancreatic cancer surgically treated at the Kobe University Hospital. The effects of gastroenteric bypass were examined by comparing the dietary intake and the symptoms of gastric outlet obstruction on admission, 1 month and 3 months after the operation. RESULTS: The analyses of dietary intake and the symptoms indicated that the gastroenteric bypass operation was not helpful for most of the patients with unresectable pancreatic cancer. Multivariate logistic regression model revealed that dietary intake on admission was the strongest parameter for dietary intake at one month after operation. The patients with a low dietary intake on admission often required a nasogastric tube after the bypass operation, reflecting progression of the disease. CONCLUSIONS: Gastroenteric bypass had no advantage to improve dietary intake and symptoms for almost all the patients with unresectable pancreatic cancer. It was effective only for patients with a high dietary intake without symptoms of gastric outlet obstruction on admission.

Proliferating cell nuclear antigen, p53, and c-erbB-2 expression in relation to clinicopathological variables and prognosis in cancer of the ampulla of Vater.

BACKGROUND/AIMS: Various clinicopathological factors have been thought to influence the prognosis of ampullary cancers. Recent advances in molecular biology should provide much useful information on the prognostic factors of ampullary carcinomas. METHODOLOGY: PCNA (proliferating cell nuclear antigen), p53, and c-erbB-2 were immunohistochemically evaluated in 30 resectable ampullary carcinomas. PCNA, p53, and c-erbB-2 expression, 6 clinicopathological variables, and prognosis were studied and correlations among these factors were investigated. RESULTS: The mean PCNA-positive rate was 39.1%. The percentages of cases positive for p53 and c-erbB-2 were 53% and 23%, respectively. No correlation was seen between PCNA, p53, or c-erbB-2 expression and clinicopathological variables. The optimum cut-off of PCNA indices influencing recurrence was decided as 40% by receiver operator characteristic curves. The cumulative disease-free survival rate of patients from the > or = 40% PCNA positive rate group was significantly poorer than that of the < 40% PCNA positive rate group (P < 0.01). p53 accumulation and c-erbB-2 expression were not correlated with prognosis. Multivariate analysis revealed that the PCNA positive rate and lymph node metastasis independently contributed to survival (P < 0.05). CONCLUSIONS: PCNA expression is a useful prognostic marker; however, p53 and c-erbB-2 overexpression are not useful as biomarkers for ampullary cancers.

Two-staged treatment with local resection and percutaneous isolated hepatic chemoperfusion for advanced pancreatic cancer with multiple liver metastases: report of a case.

There have been disappointingly few effective treatment modalities for multiple liver metastases from pancreatic cancer. Percutaneous isolated hepatic perfusion, which was developed by us for delivering dose-intensive chemotherapy to the liver, has a high efficacy in the majority of patients with multiple primary and secondary liver tumors. We herein report the first experience of a two-stage treatment with extended local resection and subsequent two percutaneous isolated hepatic perfusions for advanced pancreatic ductal adenocarcinoma with liver metastases. The second percutaneous isolated hepatic perfusion with high-dose cisplatin and mitomycin G demonstrated a distinct regression of metastatic liver tumors. Although a long-term patient survival was not obtained due to local recurrence, liver metastases have been well controlled ever since. Given that further studies establish the efficacy of percutaneous isolated hepatic perfusion also in this field, this modality would be used as prophylaxis as well as treatment of liver metastasis in patients with advanced pancreatic ductal adenocarcinoma.

Synthetic lipid A produces antitumor effect in a hamster pancreatic carcinoma model through production of tumor necrosis factor from activated macrophages.

The antitumor effect and biological activities of a newly synthesized lipid A analogue (ONO-4007) were investigated in a hamster pancreatic carcinoma model. Marked and dose-dependent inhibition of tumor growth was achieved by i.p. injection twice a week for 3 weeks of 10, 30 or 50 mg/kg of ONO-4007. Endogenous tumor necrosis factor (TNF) activities induced by ONO-4007 were significantly greater in tumor than in serum, spleen and liver. TNF production by macrophages stimulated with ONO-4007 after culture was much greater when culture was performed in the presence of hamster pancreatic carcinoma cells (no cell-to-cell contact). It was further found that the cytotoxic activity of TNF secreted by macrophages cultured with cancer cells was inhibited in the presence of anti-TNF neutralizing antibodies. These findings suggest that ONO-4007 displays antitumor effects by stimulating production of endogenous TNF in tumor macrophages, possibly through activation by soluble macrophage-stimulating factors in cancer cells.

[Treatment and present status of pancreatic cancer].

The Pancreatic Cancer Registry of the Japan Pancreas Society registered 11,317 patients of pancreatic cancer during these ten years. Among these patients, resectional procedures were performed on only 3,743 cases (33.1%). The actual 5-year survival rate of the patients who underwent resection was 16.6%. As for small cancer which was less than 2cm, the 5-year survival rate was 41.0%. In pancreatic cancer local recurrence was more frequent than other cancers of pancreatic head lesions. Extended operation which means lymphangiectomy more than R2 has not improved survival rate generally But some patients who underwent extended operation have survived long period. Multi-disciplinary treatment of pancreatic cancer has been tried.

[Retrospective analysis of postoperative chemotherapy with UFT against pancreatic cancer].

The retrospective study was carried out to evaluate the effect of UFT given orally in patients with histologically proven pancreatic cancer in our institutions for 6 years. The study regimen was designed as follows: 400 or 600 mg/body UFT per day after the patients having something solid evidences of tumor. For 6 years, 78 patients were entered in this protocol. Further details of the patients characteristics were as follows: head 47 (60.3%) cases, tail & body 31; resection cases 26 (33.3%), palliative 52; Stage IV 62 (79.5%) cases. Resection, P (peritoneal dissemination). H (liver metastasis) and T (tumor size) were statistically proven to be significant prognostic factors. The median survival time of UFT group was 204 days and that of non UFT group was 123 days. According to the retrospective analysis, there was a significant difference in the cumulative survival rate between UFT group and non UFT group with 1.98 of Hazard's proportional ratio (p = 0.009). However, further clinical investigations-prospective study are necessary to confirm these data.

[A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy].

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.

[Two cases of multiple liver metastases of colon cancer with systemic irinotecan and hepatic arterial injection of 5-FU].

We describe two patients with multiple liver metastases of colon cancer, who simultaneously received systemic irinotecan and hepatic arterial injection of 5-FU. In both cases, a notable partial response (more than 80%) in the hepatic metastases was observed. The patients could undergo chemotherapy without remarkable side-effects as out-patients. In the future, we shall perform a clinical study to evaluate the safety and dose limiting toxicity for the present combined chemotherapy.