A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer.

BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer. METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles. RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19). CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.

Evaluation of ozonated water using ASTM E1174 for standardized testing of handwash formulations for healthcare personnel.

Removal of bacteria by handwashing with ozonated water was evaluated using the ASTM E1174 standard test method. Thirty healthy volunteers were assigned randomly to three groups: ozonated water, antimicrobial soap and water, and non-antimicrobial soap and water. A 3 log10 cfu reduction was achieved by washing hands with ozonated water or antimicrobial soap and water. However, ozonated water was not significantly superior to non-antimicrobial soap and water. Ozonated water may remove bacteria from the hands to at least a similar extent as that by non-antimicrobial soap and water in the absence of visible dirt or body fluid contamination.

An increased incidence of Enterobacter cloacae in a cardiovascular ward.

Routine surveillance in a cardiovascular ward showed that the incidence of Enterobacter cloacae isolated from sputum and oropharyngeal cultures in June 2004 increased to 27.6% (8/29) compared to 5.5% (12/219) from the rest of the hospital during the same period (OR=13.2; 95% CI 2.97-58.7; P<0.05). While an increase in E. cloacae pneumonia was not verified, an investigation was undertaken by the infection control team to prevent an outbreak. The estimate of relative risk for E. cloacae infection was based on a case-control study which measured exposure to intubation, history of a stay in the intensive care unit (ICU) and oral care between patients with E. cloacae and those negative for E. cloacae. An odds ratio of 13.2 suggested cross-contamination via the transoesophageal echocardiography (TOE) probe in the ICU prior to transfer to the cardiovascular ward. Pulsed-field gel electrophoresis and antibiogram patterns were also consistent with this hypothesis. Intervention was undertaken in the form of enforcing the disinfection of TOE probes using a 0.55% phtharal solution and the use of a single-use sheath to protect the probe from recontamination. Following intervention, the incidence rate returned to previous levels. This report illustrates the limitations in the effectiveness of current nosocomial surveillance strategies due to the retrospective nature of analysis. Improved surveillance methods such as data-mining tools specifically applicable to the institution, patient population, region and country are needed to increase the sensitivity of detecting unrecognized outbreaks, including cross-contamination.

Risk of facial splashes in four major surgical specialties in a multicentre study.

This study analyses the results of face-shield blood spatter contamination at six medical facilities to determine exposure risk when facial protection is not used. Blood spatter exposure was evaluated on the basis of overall incidence, location of spatter on face shields, surgical specialty, risk for operating room staff, length of surgery and volume of blood loss. Six hundred face shields were evaluated for blood spatter contamination by visual inspection as well as by staining with leucomalachite green. The face shield was divided into three regions: Orbital (O-region), Paraorbital (P-region) and Mask (M-region). Visual examination detected blood spatter contamination in 50.5% (303/600) of the face shields, whereas leucomalachite green staining detected blood contamination in 66.0% (396/600). Blood contamination was 36.6% (220/600) in the O-region, 37.8% (227/600) in the P-region and 57.0% (342/600) in the M-region. Among operating room staff, the incidence of blood spatter was greatest among lead surgeons at 83.5% (167/200), followed by the first assistant at 68.5% (137/200) and the scrub nurse at 46.0% (92/200). By specialty, cardiovascular surgery was at highest risk with an incidence of 75.3% (113/150) followed by neurosurgery at 69.3% (104/150), gastrointestinal at 60.0% (90/150) and orthopaedic surgery at 60.0% (90/150).

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.

Pertussis outbreak among patients and healthcare workers in a provincial dialysis facility in Japan.

BACKGROUND: Sixteen pertussis cases in haemodialysis patients and healthcare workers were detected in a 25-bed outpatient haemodialysis facility in Japan between October 2013 and April 2014. AIM: To describe an outbreak of pertussis among patients and healthcare workers, and to identify risk factors for pertussis infection. METHODS: Sputum cultures, loop-mediated isothermal amplification assays performed on nasopharyngeal swabs to detect respiratory pathogens including Bordetella pertussis, and serum anti-pertussis toxin immunoglobulin G measurements were performed for all haemodialysis patients and healthcare workers. A retrospective case-control study was performed to identify the risk factors for pertussis infection in the clinic. FINDINGS: Only six of the 16 pertussis patients (37.5%) had respiratory symptoms. Recent exposure to an unmasked individual with a cough was associated with pertussis infection (odds ratio 6.25, P<0.05). The outbreak was terminated successfully after enforcing the use of surgical masks among both patients and healthcare workers. CONCLUSION: This report demonstrates the risk of pertussis transmission in a haemodialysis facility, and underscores the importance of wearing surgical masks to control a pertussis outbreak.

Outbreak of extended-spectrum ß-lactamase-producing Escherichia coli transmitted through breast milk sharing in a neonatal intensive care unit.

BACKGROUND: Routine surveillance in a neonatal intensive care unit (NICU) showed an increased detection of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-E. coli) in August 2012, following nearly a year without detection. AIM: To describe the investigation and interventions by a hospital infection control team of an outbreak of ESBL-E. coli in a NICU. METHODS: Six neonates with positive cultures of ESBL-E. coli (five with respiratory colonization, one with a urinary tract infection), control infants who were negative for ESBL-E. coli during the study period, and mothers who donated their breast milk were included. A case-control study was performed to identify possible risk factors for positive ESBL-E. coli cultures and molecular typing of isolated strains by pulsed-field gel electrophoresis. FINDINGS: The odds ratio for ESBL-E. coli infection after receiving shared unpasteurized breast milk during the study period was 49.17 (95% confidence interval: 6.02-354.68; P < 0.05). The pulsed-field gel electrophoresis pattern showed that all strains were identical, and the same pathogen was detected in freshly expressed milk of a particular donor. After ceasing the breast milk sharing, the outbreak was successfully terminated. CONCLUSION: This outbreak indicates that contamination of milk packs can result in transmission of a drug-resistant pathogen to newborn infants. Providers of human breast milk need to be aware of the necessity for low-temperature pasteurization and bacterial cultures, which should be conducted before and after freezing, before prescribing to infants.

Pigment epithelium-derived factor induces pro-survival genes through cyclic AMP-responsive element binding protein and nuclear factor kappa B activation in rat cultured cerebellar granule cells: Implication for its neuroprotective effect.

Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cell neurons (CGCs) against apoptosis induced by K+ and serum deprivation. However, the precise mechanism of this protection remains unknown. We recently reported that the transcription factor nuclear factor kappa B (NF-kappaB) is activated in PEDF-treated CGCs. Although it is well known that NF-kappaB blocks apoptotic cell death through the induction of pro-survival factors, the effects of PEDF on the expression of these factors are not fully understood. In this study, we employed the use of reverse transcriptase-polymerase chain reaction to analyze the gene expression of certain pro-survival genes and found that genes such as c-IAP1, c-IAP2, FLIPs, A1/Bfl-1 and Mn-SOD were induced in PEDF-treated neurons. On the other hand, no induction was observed of the pro-apoptotic Bcl-2 family members Bax and Bid at any time from 3 to 24 h following PEDF addition. Furthermore, phosphorylation of cyclic AMP-responsive element binding protein (CREB) and increment of nuclear cyclic AMP-response element (CRE)-like DNA binding were observed in PEDF-treated CGCs. The anti-apoptotic effect of PEDF was blocked by overexpression of dominant negative CREB or a mutated form of IkappaBalpha. These results suggested that induction of both CRE- and NF-kappaB-dependent genes is required for the observed neuroprotective effects of PEDF on CGCs.

Does incineration turn infectious waste aseptic?

Incineration of infectious waste is considered to be biologically safe. We performed basic experiments to confirm that bacillus spores are killed by incineration in a muffle furnace. Biological samples containing 10(6) spores of Bacillus stearothermophilus were placed in stainless steel Petri dishes and then into hot furnaces. The furnace temperature and duration of incineration were 300 degrees C for 15 min, 300 degrees C for 30 min, 500 degrees C for 15 min, 500 degrees C for 30 min and 1100 degrees C for 3 min. We confirmed that all spores of B. stearothermophilus were killed at each of these settings. The effect of incineration seems to be equivalent to that of sterilization, based on the satisfactory sterilization assurance level of 10(-6).

Residual formaldehyde on plastic materials and medical equipment following low-temperature steam and formaldehyde sterilization.

We measured the amount of residual formaldehyde on 16 plastic materials and five medical devices following low-temperature steam and formaldehyde (LTSF) sterilization, based on the European Standard EN14180. The amounts of formaldehyde residue on the plastic materials were compared with that on a filter paper of similar dimensions. The amount of residual formaldehyde on polyamide 6, polyurethane, natural rubber and polyacetal was higher (21.9, 15.2, 3.0 and 2.1 times, respectively) than that on the filter paper. The amount of formaldehyde recovered from a breathing circuit, anaesthesia circuit, oxygen tubing, airway tube and tweezers was 260, 240, 594, 56 and 0 microg, respectively, following LTSF sterilization. Our results emphasize the need to verify the main material composing the medical equipment before LTSF sterilization, as the amount of formaldehyde retrieved following sterilization varies according to the material used for construction.

Lymphatic spreading pattern of intrahepatic cholangiocarcinoma.

BACKGROUND: There have been very few reports on the pattern of lymphatic spread of intrahepatic cholangiocarcinoma. This pattern was elucidated to help define the rational extent of radical lymph node dissection. METHODS: Thirty-nine consecutive patients who underwent hepatectomy with radical lymph node dissection were reviewed retrospectively. RESULTS: Lymph node metastases were detected in 24 of the 39 patients (62%). The metastatic nodes were found in the hepatoduodenal ligament, along the common hepatic artery, around the abdominal aorta, on the posterior surface of the pancreas head, along the left gastric artery, along the superior mesenteric artery, around the celiac artery, along the lesser curvature of the stomach, and around the cardia. The nodal involvements along the left gastric artery, along the lesser curvature, or around the cardia were recognized only in the left peripheral and hilar types of cholangiocarcinoma, while all other sites included both the left or right peripheral type and the hilar type cholangiocarcinoma. CONCLUSIONS: Intrahepatic cholangiocarcinomas, irrespective of their intrahepatic location, mainly spread to the nodes in the hepatoduodenal ligament, then to the para-aortic nodes, retropancreatic nodes, or common hepatic artery nodes. In addition to these spreading routes, the left peripheral type or hilar type of cholangiocarcinoma tends to spread along the left gastric nodes through the lesser curvature.

Prolongation of survival for carcinoma at the hepatic duct confluence.

BACKGROUND: Because of poor long-term results in resection for carcinoma at the hepatic duct confluence, we have adopted a more aggressive approach. METHODS: The records of 46 patients with carcinoma of the hepatic duct confluence were reviewed. Twenty-four patients underwent hepatic resection and 10 underwent local resection. The remaining 12 patients had unresectable lesions and received palliative treatment. Out of 24 patients who underwent hepatic resection, 17 underwent combined resection of the caudate lobe. Five patients who underwent hepatic resection and three patients who underwent local resection received intraoperative radiotherapy in a dose of 30 Gy of electron beam. Postoperative radiotherapy with a total dose of 50 Gy of external electron beam was performed for five patients who underwent nonradical hepatic resection and one patient who underwent nonradical local resection. RESULTS: None of the 10 patients who underwent local resection and only 1 (4.2%) of 24 patients who underwent hepatic resection died in the hospital. Among patients who underwent hepatic resection, the 1-, 3-, and 5-year survival rates were 62%, 37%, and 25%, respectively, whereas the respective survival rates in the group that underwent local resection were 50%, 20%, and 20%. The 1-, 3-, and 5-year survival rates for patients who underwent combined caudate lobectomy were 69.7%, 53.4%, and 23%, respectively, compared with 57.1%, 26%, and 14.3% for those who did not. The median survival time for patients who received radiotherapy after nonradical resection was 17 months, compared with 5 months for those who did not. CONCLUSIONS: These results suggest that major hepatic resection combined with caudate lobectomy should be performed for carcinoma of the heptic duct confluence. Postoperative radiotherapy after nonradical resection may be effective in prolonging survival.

Evaluation of a low-temperature steam and formaldehyde sterilizer.

We evaluated a low-temperature steam and formaldehyde (LTSF) sterilizer based on the draft European Standard prEN 14180. Microbiological tests were conducted on small and full loads using process challenge devices in five programs (P1-P5). With small loads all tests showed no growth of Bacillus stearothermophilus (ATCC7953) spores. However, positive cultures were observed with full-load tests using P5 (sterilization temperature, 50 degrees C). Our data indicated that the load influenced the efficacy of the LTSF sterilizer. Desorption tests were conducted to determine residual formaldehyde in indicator strips. The mean concentrations of formaldehyde in P1-P5 were 31.9, 56.3, 54.9, 82.2 and 180.6 microg, respectively, which are below the limits allowed by the draft Standard. Our results indicate that the LTSF sterilizer is useful for sterilization because of its excellent efficacy, short handling time, and safety.

Quantitative determination of gelatinase activity among enterococci.

Gelatinase, hemolysin and aggregation substance have all been reported to be virulence factors of enterococci. In this study, gelatinase production was investigated in isolates of Enterococcus faecalis (n=93), E. faecium (n=49) and E. avium (n=36) recovered from hospitalized patients. Gelatinase was detected in 45% of E. faecalis isolates, but could not be detected in E. faecium and E. avium. Gelatinase activity was then measured by radial diffusion for the 42 gelatinase-positive E. faecalis isolates. To convert gelatinase activity into proteinase K activity, a standard curve was produced by placing different concentrations of proteinase K into wells in the gelatine plate. Gelatinase activity per E. faecalis colony ranged from 2.6 x 10(-7) to 2.2 x 10(-5) microg/ml, proportionate to the activity of proteinase K. An approximately 84-fold difference in gelatinase concentration was observed between the colony producing the highest amount and that producing the lowest amount. This method may be useful for determining the virulence of given isolates in relation to gelatinase production as it is quick, easy and inexpensive to perform.

Carcinoembryonic antigen (CEA) and CEA-related substances in the bile of patients with biliary diseases.

The levels of carcinoembryonic antigen (CEA) in the bile of 10 patients with biliary cancer and 9 patients with cholelithiasis were examined immunochemically by the Western blot analysis. All samples of bile from the patients with biliary cancer showed three bands that corresponded to CEA, nonspecific crossreacting antigen, and biliary glycoprotein 1, respectively. The upper band (CEA) disappeared from the bile of patients who underwent curative operations, but it persisted in the bile of patients who underwent noncurative operations. All samples of bile from the patients with cholelithiasis did not show the upper band (CEA), even in those samples that had high levels of CEA by the conventional enzyme immunoassay. We suggest that, in order to diagnose the presence of tumor, to assess the therapeutic efficacy of surgery, and to detect any residual tumor, not only should the level of bile CEA be measured but also a Western blot analysis of the bile should be performed since it is more reliable.

A new surgical approach for control of pain in chronic pancreatitis: complete denervation of the pancreas.

With the aim of pain control in chronic pancreatitis without the morbidity of insulin-dependent diabetes, a new procedure was devised to completely resect the postganglionic pancreatic nerves and to totally free the pancreas from the posterior abdominal wall. This procedure was performed on two patients with follow-up periods of 24 and 10 months. Pain was resolved in both patients, and their blood glucose levels were substantially unchanged. This new approach offers a means of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis, especially in patients who have a small pancreatic duct.

A method for safe pancreaticojejunostomy.

We devised a new technique to increase the safety of pancreaticojejunostomy in patients with an extended operation for pancreatic cancer. This new pancreaticojejunostomy was created by end-to-side anastomosis with four layers about 7 cm distal to the jejunal stump. The cut surface of the pancreas was placed on the seromuscular coat of the ventral aspect of the jejunum to cover the posterior surface of the anastomosis, and the anastomosis between the pancreas and the jejunum was created using fibrin glue. The pancreatic duct was intubated with a silicone tube, and its stenting tube was brought out through a opening in the jejunum. The anterior surface of the pancreaticojejunostomy was covered by the proximal jejunum as a serosal patch. We used this technique in seven patients. No patient developed an anastomotic leak or any other complication. The anastomosis is covered by the jejunum and is not open to the peritoneum. This new technique of pancreaticojejunostomy may reduce the risk of pancreatic leak, especially when an extended operation is performed.

Effect of cephalosporins on gamma-aminobutyric acid receptor binding with or without non-steroidal anti-inflammatory drugs.

Cephalosporins have been well known to have potent convulsant activity. We studied the mechanism of the convulsions induced by cephalosporins. Cefazolin, cephaloridine, cefpirome and cefmetazole inhibited the receptor binding of gamma-aminobutyric acid (GABA), an inhibitory transmitter in the mammalian central nervous system. As fluoroquinolones also inhibited GABA receptor binding and this inhibition was enhanced in the presence of non-steroidal anti-inflammatory drugs (NSAIDs), we studied the effect of cephalosporins on GABA receptor binding in the presence of NSAIDs. The inhibitory activity of cephalosporins was not enhanced in the presence of NSAIDs. These results suggested that cephalosporins might induce convulsions through the inhibition of GABA receptor binding, and that concurrent administration of cephalosporins and NSAIDs might not enhance the convulsant activity of cephalosporins.

Everninomicin, a new oligosaccharide antibiotic: its antimicrobial activity, post-antibiotic effect and synergistic bactericidal activity.

Antimicrobial activity of everninomicin (SCH) 27899) in comparison with two glycopeptides (vancomycin, teicoplanin) and six beta-lactam agents was evaluated against recent clinical isolates of Gram-positive bacteria. Everninomicin showed the highest activity against the species tested and MICs90% of everninomicin against Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Clostridium difficile were 0.1, 0.1, 0.2, 0.39, 0.1 microgram/ml, respectively. MICs90% of everninomicin against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were 0.78 microgram/ml. Laboratory induced resistance to everninomicin in strains of S. aureus and E. faecalis occurred in a stepwise manner and at a very slow rate. Post-antibiotic effect against strains of S. aureus and E. faecalis were 1.8 and 2.6 h, respectively, and a little longer than that of vancomycin. Adherence to glass surface of an MRSA strain was strongly repressed by the addition of sub MIC of everninomicin in combination with fosfomycin.

A comparative study on the convulsant activity of carbapenems and beta-lactams.

Beta-lactams are well known to have potent convulsant activity. Imipenem, the first carbapenem antibiotic introduced in the clinical field, has been reported to induce convulsions. The neurochemical mechanism of the convulsions induced by carbapenems and cephalosporins were studied. Intraventricular injection of cefazolin, cephaloridine and imipenem, and of panipenem (a new carbapenem), induced convulsions in a dose-dependent manner in mice. They inhibited the receptor binding of gamma-aminobutyric acid (GABA), an inhibitory transmitter in the mammalian central nervous system. These in-vitro and in-vivo results suggest that carbapenems and cephalosporins might induce convulsions through the inhibition of GABA receptor binding when they are accumulated in the central nervous system.