Pylorus-Resecting Pancreaticoduodenectomy Offers Long-Term Outcomes Similar to Those of Pylorus-Preserving Pancreaticoduodenectomy: Results of a Prospective Study

Background

We showed in a previous study that pylorus-resecting pancreaticoduodenectomy (PrPD), which divides the stomach adjacent to the pylorus ring, preserves more than 95 % of the stomach and significantly reduced the incidence of delayed gastric emptying (DGE) compared with pylorus-preserving pancreaticoduodenectomy (PpPD). However, long-term outcomes of PrPD and the adverse effect of early postoperative DGE on long-term outcomes remain unclear.

Methods

A total of 130 patients enrolled in a previous study were followed for 24 months after surgery. Primary endpoint was whether PrPD is a better surgical procedure than PpPD regarding long-term outcomes.

Results

Weight loss > grade 2 (Common Terminology Criteria for Adverse Events, Version 4.03) at 24 months after surgery was significantly better in group PrPD (16.2 %) than in group PpPD (42.2 %) (p = 0.011). Nutritional status and late postoperative complications were similar for the two groups. The incidence of weight loss > grade 2 at 24 months was 63.6 % in DGE patients with DGE and 25.3 % in non-DGE patients (p = 0.010). T _max (time to peak ¹³CO₂ content in ¹³C-acetate breath test) at 24 months in DGE patients was significantly delayed compared with that in non-DGE patients (27.9 ± 22.7 vs. 16.5 ± 10.1 min, p = 0.023). Serum albumin level at 24 months was higher in non-DGE patients than in those with DGE (3.7 ± 0.6 vs. 4.1 ± 0.4 g/dl, p = 0.013).

Conclusions

PrPD offers long-term outcomes similar to those of PpPD. DGE may be associated with weight loss and poor nutritional status in patients with long-term outcomes.     

Safety of bioabsorbable membrane (Seprafilim®) in hepatectomy in the era of aggressive liver surgery

BackgroundRepeat hepatectomy has been recognized as an effective treatment for hepatic malignancies, and a sheet type adhesion barrier, Seprafilm® has increasingly been used during hepatectomy to ease future relaparotomy. However, there is not yet sufficient evidence to support the safety of use of Seprafilm in liver surgery.MethodsData of 151 patients who had undergone open hepatectomy were retrospectively reviewed and the incidence of major abdominal morbidity was compared between patients in whom Seprafilm had and had not been used.ResultsSeprafilm was used in 108 patients (Seprafilm group) and no adhesion barrier was used in 43 patients (comparison group). There was no significant difference in the rate of major abdominal morbidities between the two groups (Seprafilm vs. comparison: 10% vs. 16%, P = 0.403). Although the Seprafilm group showed a tendency toward increased incidence of bile leakage (7% vs. 2%), and placement of Seprafilm on the hepatoduodenal ligament or on the visceral surface of the liver seemed to be associated with an increased incidence of major morbidity, multivariate analysis showed no significant correlation between the use of Seprafilm and postoperative major abdominal morbidity.ConclusionUse of Seprafilm may not increase the risk of major abdominal morbidity in liver surgery.     

Genetic Analysis of the Complete S1 Gene in Japanese Infectious Bronchitis Virus Strains

The complete nucleotide sequence of the S1 glycoprotein gene of the Japanese infectious bronchitis virus (IBV) strains was determined and genetically analyzed. A total of 61 Japanese IBV strains were classified into seven genotypes, namely GI-1, 3, 7, 13, 18, 19, and GVI-1 using the classification scheme that was proposed by Valastro et al, with three exceptions. These genotypes practically corresponded to those defined in Japan, namely Mass, Gray, JP-II, 4/91, JP-I, JP-III, and JP-IV, which have been identified through their partial nucleotide sequences containing hypervariable regions 1 and 2. In addition, three exceptive strains were considered to be derived from recombination within the S1 gene of IBV strains G1-13 and GI-19. By analyzing the amino acid polymorphism of the S1 glycoprotein among Japanese genotypes, a diversity was observed based on the genotype-specific amino acid residue, the proteolytic cleavage motif at the S1/S2 cleavage site, and the position of the potential N-glycosylation sites.     

The Evaluation of Duct-to-mucosal Pancreaticojejunostomy in pancreaticoduodenectomy

This study was conducted to examine the efficacy of duct-to-mucosal pancreaticojejunostomy compared with external stented pancreaticojejunostomy in prevention of several complications, retrospectively. Seventy-six patients with pancreatic head resection (59 male; median age, 60.1 years) underwent pancreaticoduodenectomy at the Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan, between January 1, 1994, and March 31, 2002. In early postoperative status, the incidence of pancreatic fistula by duct-to-mucosal anastomosis (n = 45) was similar to that by external stent (n = 31); soft pancreas is a risk factor of pancreatic fistula compared with hard pancreas (p < 0.05). During the late postoperative period, however, no patients with duct-to-mucosal anastomosis showed pancreatic duct dilatation by computed tomography (CT). At the same time, 58.8% of patients with external stent followed by CT showed pancreatic duct dilatation (p < 0.01). The duct-to-mucosal anastomosis was more effective pancreaticojejunostomy than the external stent in terms of prevention of pancreatic duct dilatation, and it should be the surgical procedure of choice in pancreaticoduodenectomy.     

Respiratory muscle stretch gymnastics in patients with post coronary artery bypass grafting pain: impact on respiratory muscle function,activity, mood and exercise capacity

A new rehabilitation (New-RH) program including respiratory muscle stretch gymnastics (RMSG) was developed to alleviate post-coronary artery bypass grafting pain (PCP). Effects on respiratory muscle function, pain, activities of daily living (ADL), mood and exercise capacity were investigated. Subjects were 16 consecutive patients undergoing median full sternotomy coronary artery bypass grafting (CABG), and were randomly divided into equal New-RH (S-group) and conventional therapy (C-group) groups. Rib cage dominant breathing was observed postoperatively in both groups. With preoperative tan deltaVrc/deltaVab, increases at 1-week postoperatively and decreases at discharge for S-group tended to exceed those of C-group (p > .05). Decreased maximum inspiratory and expiratory pressure status for functional residual capacity and percent forced expiratory volume in one second at discharge again only tended to be smaller for S-group (p > .05). S-group displayed significantly reduced pain around both scapulas at discharge (p = .049), and increased mean overall ADL and profile of mood states (POMS)/Vigor scores (p = .031 and p = .018, respectively). POMS/Tension-Anxiety scores at discharge for S-group were significantly smaller than those preoperatively (p = .025), and S-group displayed significantly increased distance walked over 6-minutes at discharge than C-group (p = .029). New-RH improves patient participation in exercise therapy and increases exercise capacity by reducing PCP, relieving anxiety and tension, and improving ADL.     

Role of a mutation at position 167 of CTX-M-19 in ceftazidime hydrolysis

CTX-M-19 is a recently identified ceftazidime-hydrolyzing extended-spectrum beta-lactamase, which differs from the majority of CTX-M-type beta-lactamases that preferentially hydrolyze cefotaxime but not ceftazidime. To elucidate the mechanism of ceftazidime hydrolysis by CTX-M-19, the beta-lactam MICs of a CTX-M-19 producer, and the kinetic parameters of the enzyme were confirmed. We reconfirmed here that CTX-M-19 is also stable at a high enzyme concentration in the presence of bovine serum albumin (20 micro g/ml). Under this condition, we obtained more accurate kinetic parameters and determined that cefotaxime (k(cat)/K(m), 1.47 x 10(6) s(-1) M(-1)), cefoxitin (k(cat)/K(m), 62.2 s(-1) M(-1)), and aztreonam (k(cat)/K(m), 1.34 x 10(3) s(-1) M(-1)) are good substrates and that imipenem (k(+2)/K, 1.20 x 10(2) s(-1) M(-1)) is a poor substrate. However, CTX-M-18 and CTX-M-19 exhibited too high a K(m) value (2.7 to 5.6 mM) against ceftazidime to obtain their catalytic activity (k(cat)). Comparison of the MICs with the catalytic efficiency (k(cat)/K(m)) of these enzymes showed that some beta-lactams, including cefotaxime, ceftazidime, and aztreonam showed a similar correlation. Using the previously reported crystal structure of the Toho-1 beta-lactamase, which belongs to the CTX-M-type beta-lactamase group, we have suggested characteristic interactions between the enzymes and the beta-lactams ceftazidime, cefotaxime, and aztreonam by molecular modeling. Aminothiazole-bearing beta-lactams require a displacement of the aminothiazole moiety due to a severe steric interaction with the hydroxyl group of Ser167 in CTX-M-19, and the displacement affects the interaction between Ser130 and the acidic group such as carboxylate and sulfonate of beta-lactams.     

Dietary nucleic acid and intestinal microbiota synergistically promote a shift in the Th1/Th2 balance toward Th1-skewed immunity

BACKGROUND: Intestinal microbiota are known to play an important role in the establishment of oral tolerance, thereby protecting the organism from food allergies. Dietary intake of nucleic acid (NA) is also reported to have such an anti-allergic effect; however, one unsolved question is whether or not dietary NA would act through a process of toll-like receptor 9 signaling activated by DNA containing a CpG motif, a well-known sequence leading to immunostimulatory activity. In this study, we focused on the question of whether the addition of dietary NA lacking CpG motifs would allow continued modulation of the Th1/Th2 balance. METHODS: Germ free (GF) and Bifidobacterium-infantis-monoassociated BALB/c mice were maintained on either an NA-free casein diet or on an NA-supplemented casein diet for 4 weeks. Thereafter, both the in vivo anti-casein antibody levels and in vitro splenocyte cytokine secretion pattern were evaluated. RESULTS: Feeding with a casein diet elicited a substantial increase in the serum anti-casein-specific IgG1, IgG2a, and IgE levels of GF mice fed the NA free-diet. The in vitro cytokine production profile showed that enhanced IL-4 production in the GF mice fed the NA free-diet was markedly reduced by the supplementation with dietary NA in both the GF and B.-infantis-monoassociated mice. In addition, IFN-gamma secretion increased in the B.-infantis-reconstituted mice fed the diet containing NA. CONCLUSIONS: These results suggest that dietary intake of NA devoid of CpG motifs may prevent the development of allergies via acceleration of Th1-dominant immunity.     

Potential Function of Granulysin,Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9⁺Vδ2⁺ T cells, CD4⁺ T cells and CD8⁺ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8⁺ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.     

cDNA microarray analysis of individual Duchenne muscular dystrophy patients

We have developed a novel cDNA microarray encompassing 3500 genes expressed in skeletal muscle. With this system, we have performed the first study of gene expression in samples from individual patients. We analyzed muscle specimen from individuals with Duchenne muscular dystrophy to identify differences among patients. Among the variably expressed genes, we focused on the expression of the genes encoding HLA-related proteins, myosin light chains and troponin Ts as markers of muscle necrosis and regeneration. The expression patterns of these genes correlated with the severity of dystrophic changes on histological examination. Our cDNA microarray provides a new tool to investigate molecular muscle pathology.