Management of isolated recurrence after surgery for pancreatic adenocarcinoma.

BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.

Hepatic stellate cells induce immunotolerance of islet allografts.

Activated hepatic stellate cells (HSCs) possess strong immune inhibitory activity. The present study highlighted the protective role of HSCs in islet transplantation. Recipients were randomly divided into 4 groups: a diabetic group, an HSC-alone group, an islet-alone transplant group, and a cotransplant group. Graft survival was compared among the 4 groups. Serum transforming growth factor ß (TGFß), tumor necrosis factor α, interleukin-1ß, and interferon gamma expression levels were measured. The infiltration of lymphocytes was observed via hematoxylin and eosin staining, and immunohistochemical examinations were performed. Results showed that allogeneic HSCs protect islet allografts better than syngeneic HSCs. There was significant prolonged graft survival and a higher level of TGFß in the cotransplant group (P < .01). The infiltration of lymphocytes in the cotransplant group was notably less than in the islet-alone group (P < .01). The formation of desmin-positive HSC packages was detected in the cotransplant group. In conclusion, allogeneic HSCs can better prolong the survival of islet allografts by stimulating TGFß expression and forming a biological capsule around the graft.

Adult dual kidney transplantations obtained from marginal donors: two case reports.

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts.

Effects of various plasticizers and nanoclays on the mechanical properties of red algae film.

UNLABELLED: To manufacture red algae (RA) film, we used various plasticizers such as glycerol, sorbitol, sucrose, fructose, and polypropylene glycol (PPG), and then determined the mechanical properties of the RA films. The tensile strength (TS), elongation at break (E), and water vapor permeability (WVP) of the films containing various plasticizers ranged between 0.43 to 9.10 MPa, 10.93% to 47.17%, and 1.28 to 1.42 ng m/m2sPa, respectively. RA films containing fructose as a plasticizer had the best mechanical properties of all the films evaluated. Incorporation of nanoclay (Cloisite Na+ and 30B) improved the mechanical properties of the films. RA film with 3% Cloisite Na+ had a TS of 10.89, while RA film with 30B had a TS of 10.85 MPa; these films also had better E and WVP values than the other RA films evaluated. These results suggest that RA/nanoclay composite films are suitable for use as food packaging materials. PRACTICAL APPLICATION: Edible RE/nanoclay composite films prepared in the present investigation can be applied in food packaging.

A case of disseminated extrahepatic hepatocellular carcinoma after US-guided biopsy and percutaneous ethanol injection therapy.

A case of disseminated extrahepatic hepatocellular carcinoma (HCC) occurring after ultrasound (US)-guided biopsy and percutaneous ethanol injection therapy is presented. A 72-year-old man with hepatitis-C-virus-related cirrhosis underwent percutanous ethanol injection therapy (PEIT) two times with complete remission: the first for moderately-differentiated HCC in segment six (S6), and the second for well-differentiated HCC in another part of S6. Imaging studies including carbon dioxide (CO(2))-US angiography, incremental computed tomography, and dynamic magnet resonance imaging showed that both HCCs were hypovascular. Twenty-one months after the first PEIT and 7 months after the second, a 5.5x4.5 cm extrahepatic mass interfaced with S6 of the liver was detected by imaging studies. The patient underwent surgery for extrahepatic HCC. Grossly, the main tumor was 5.5x4.5 cm with capsule and septum; the disseminated tumors were detected on the surface of the liver, including the right diaphragm and the falx ligamentosa. Histologically, it was moderately- to poorly-differentiated HCC, which, although not attributed to direct track seeding, was suspected of being induced by the percutaneous US-guided biopsy procedure or by PEIT, irrespective of a hypovascular tumor. Further studies may provide insight into the risk factor engendered by these procedures.

Exposure to volatile organic compounds for individuals with occupations associated with potential exposure to motor vehicle exhaust and/or gasoline vapor emissions.

Workers who work near volatile organic compounds (VOCs) source(s), motor vehicle exhausts and/or gasoline vapor emissions, are suspected to be exposed to highly-elevated VOC levels during their work-time. This study confirmed this suspicion and evaluated the work-time exposure VOCs for traffic police officers, parking garage attendants, service station attendants, roadside storekeepers and underground storekeepers, by measuring the concentrations of six aromatic VOCs in workplace air, or personal air and breath samples. For nearly all target VOCs, the post-work breath concentrations of the workers were slightly or significantly higher than the pre-work breath concentrations, depending on the compound and occupation. Furthermore, both the pre- and post-work breath concentrations of the workers showed elevated levels compared with a control group of college students. The post-work breath concentrations were significantly correlated with the personal air concentrations, while the pre-work breath concentrations were not. Smoking workers were not always exposed to higher aromatic VOC levels than non-smoking workers. The breath and personal air concentrations for all the target compounds were both higher for underground parking garage attendants than for ground-level parking attendants. For all the target compounds except toluene, storekeepers exhibited similar levels of exposure for all store types. Print shopkeepers recorded the highest toluene exposure.

TTV positivity and transfusion history in non-B, non-C hepatocellular carcinoma compared with HBV- and HCV-positive cases.

The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63. 6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: difficulty in differentiating it from hepatocellular carcinoma.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3-E1 cells.

Bone formation involves several tightly regulated gene expression patterns of bone-related proteins. To determine the expression patterns of bone-related proteins during the MC3T3-E1 osteoblast-like cell differentiation, we used Northern blotting, enzymatic assay, and histochemistry. We found that the expression patterns of bone-related proteins were regulated in a temporal manner during the successive developmental stages including proliferation (days 4-10), bone matrix formation/maturation (days 10-16), and mineralization stages (days 16-30). During the proliferation period (days 4-10), the expression of cell-cycle related genes such as histone H3 and H4, and ribosomal protein S6 was high. During the bone matrix formation/maturation period (days 10-16), type I collagen expression and biosynthesis, fibronectin, TGF-beta 1 and osteonectin expressions were high and maximal around day 16. During this maturation period, we found that the expression patterns of bone matrix proteins were two types: one is the expression pattern of type I collagen and TGF-beta 1, which was higher in the maturation period than that in both the proliferation and mineralization periods. The other is the expression pattern of fibronectin and osteonectin, which was higher in the maturation and mineralization periods than in the proliferation period. Alkaline phosphatase activity was high during the early matrix formation/maturation period (day 10) and was followed by a decrease to a level still significantly above the baseline level seen at day 4. During the mineralization period (days 16-30), the number of nodules and the expression of osteocalcin were high. Osteocalcin gene expression was increased up to 28 days. Our results show that the expression patterns of bone-related proteins are temporally regulated during the MC3T3-E1 cell differentiation and their regulations are unique compared with other systems. Thus, this cell line provides a useful in vitro system to study the developmental regulation of bone-related proteins in relation to the different stages during the osteoblast differentiation.

Molecular properties of lysine-2,3-aminomutase.

Lysine-2,3-aminomutase purified from Clostridium subterminale SB4 is reported to exhibit an apparent subunit Mr of 48,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the undenatured enzyme exhibits an apparent Mr of 285,000, as determined by electrophoretic mobility and gel permeation chromatography (Chirpich, T. P., Zappia, V., Costilow, R. N., and Barker, H. A. (1970) J. Biol. Chem. 245, 1778-1789). The diffusion coefficient of the enzyme is 3.36 x 10(-7) cm2/s, as determined by quasielastic light scattering. The overall Mr calculated from the diffusion coefficient and the published sedimentation coefficient is 259,000. Cross-linking experiments using glutaraldehyde and dithiobis(succinimidylpropionate) as cross-linking reagents indicate that the enzyme has a hexameric quaternary structure. The number of major cyanogen bromide peptides, compared with the methionine content of the enzyme, is consistent with the subunits being identical, and isoelectric focusing also is consistent with identical subunits. The circular dichroism of the enzyme indicates that it is a highly ordered structure, which is estimated to consist of 26% alpha-helix and 48% beta-sheet. The enzyme contains approximately six molecules of pyridoxal 5'-phosphate per hexamer, as determined by the phenyl-hydrazine method. The amino acid analysis of the enzyme, after performic acid oxidation, indicates that it contains approximately 13 cysteine residues per subunit. Six sulfhydryl groups per hexamer react readily with 5,5'-dithiobis-2-nitrobenzoate, indicating that one sulfhydryl group is accessible per subunit.

Construction of a chimeric series of Bacillus cyclomaltodextrin glucanotransferases and analysis of the thermal stabilities and pH optima of the enzymes.

The cyclomaltodextrin glucanotransferase (CGTase, EC 2.4.1.19) gene from the alkalophilic Bacillus sp. strain no. 17-1 was cloned in Escherichia coli. The cloned CGTase gene consisted of a single open reading frame which would encode a polypeptide of 713 amino acids, and the first 27 amino acid residues comprised a signal peptide. The nucleotide sequence and the amino acid sequence of this CGTase (CGTase 17-1) gene had strong homology with those of the CGTase (CGTase 38-2) gene previously cloned in our laboratory from the alkalophilic Bacillus sp. strain no. 38-2, although the enzymic properties of the CGTase 17-1 were distinct from those of the CGTase 38-2. To analyse those enzymic properties further, we constructed 12 chimeric CGTases using three restriction nuclease sites and compared the enzymic properties of the chimeric CGTases. The N-terminal part of the enzyme was important for heat stability, and the pH-activity profile was influenced by both the N- and the C-terminal parts. A third segment was less important for enzymic properties.

Requirement for a sulfhydryl group for sulfhydryl oxidase activity.

Sulfhydryl oxidase was isolated from bovine skim milk membranes using a transient covalent affinity chromatographic method. This preparation exhibited two chemically reactive sulfhydryl groups in the native enzyme and three in the denatured form, based on a subunit weight of 85 kdaltons. The kinetics of inactivation by carboxymethylation with iodoacetate indicated that modification of one sulfhydryl group per enzyme subunit caused complete loss of activity. These results, together with the enzyme's attachment to cysteinylsuccinamidopropyl-glass and the observed initial rate enzyme kinetics, strongly implicate a substituted-enzyme kinetic mechanism with a mixed disulfide as the intermediate enzyme form.