Realistic Advantages of Early Surgical Drain Removal after Pancreatoduodenectomy: A Single-Institution Retrospective Study.

The latest guidelines from the Enhanced Recovery After Surgery (ERAS®) Society stated that early drain removal after pancreatoduodenectomy (PD) is beneficial in decreasing complications including postoperative pancreatic fistulas (POPFs). This study aimed to ascertain the actual benefits of early drain removal after PD. The data of 450 patients who underwent PD between 2018 and 2020 were retrospectively reviewed. The surgical outcomes were compared between patients whose drains were removed within 3 postoperative days (early removal group) and after 5 days (late removal group). Logistic regression analysis was performed to identify the risk factors for clinically relevant POPFs (CR-POPFs). Among the patients with drain fluid amylase < 5000 IU on the first postoperative day, the early removal group had fewer complications and shorter hospital stays than the late removal group (30.9% vs. 54.5%, p < 0.001; 9.8 vs. 12.5 days, p = 0.030, respectively). The incidences of specific complications including CR-POPFs were comparable between the two groups. Risk factor analysis showed that early drain removal did not increase CR-POPFs (p = 0.163). Although early drain removal has not been identified as apparently beneficial, this study showed that it may contribute to an early return to normal life without increasing complications.

Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods.

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)-which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue-exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.

Prognostic Role of TMED3 in Clear Cell Renal Cell Carcinoma: A Retrospective Multi-Cohort Analysis.

Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC. Patient data were extracted from cohorts in the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Differential expression of TMED3 was observed between the low stage (Stage I and II) and high stage (Stage III and IV) patients in the TCGA and ICGC cohorts and between the low grade (Grade I and II) and high grade (Grade III and IV) patients in the TCGA cohort. Further, we evaluated TMED3 expression as a prognostic gene using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristics at 5 years. The Kaplan-Meier analysis revealed that TMED3 overexpression was associated with poor prognosis for ccRCC patients. Analysis of the C-indices and area under the receiver operating characteristic curve further supported this. Multivariate analysis confirmed the prognostic significance of TMED3 expression levels (P = 0.005 and 0.006 for TCGA and ICGC, respectively). Taken together, these findings demonstrate that TMED3 is a potential prognostic factor for ccRCC.

Comparison analysis of left-side versus right-side resection in bismuth type III hilar cholangiocarcinoma.

BACKGROUNDS/AIMS: Several studies report worse prognosis after left-side compared to right-side liver resection in patients with perihilar cholangiocarcinoma. In this study, we compared outcomes of left-side and right-side resections for Bismuth type III hilar cholangiocarcinoma and analyzed factors affecting survival. METHODS: From May 1995 to December 2012, 179 patients underwent surgery at Samsung Medical Center for type III hilar cholangiocarcinoma. Among these patients, 138 received hepatectomies for adenocarcinoma with curative intent: 103 had right-side resections (IIIa group) and 35 had left-side resections (IIIb group). Perioperative demographics, morbidity, mortality, and overall and disease-free survival rates were compared between the groups. RESULTS: BMI was higher in the IIIa group (24±2.6 kg/m2 versus 22.7±2.8 kg/m2; p=0.012). Preoperative portal vein embolization was done in 23.3% of patients in the IIIa group and none in the IIIb group. R0 rate was 82.5% in the IIIa group and 85.7% in the IIIb group (p=0.796) and 3a complications by Clavien-Dindo classification were significantly different between groups (10.7% for IIIa versus 23.3% for IIIb; p=0.002). The 5-year overall survival rate was 33% in the IIIa group and 35% in the IIIb group (p=0.983). The 5-year disease-free survival rate was 28% in the IIIa group and 29% in the IIIb group (p=0.706). Advanced T-stages 3 and 4 and LN metastasis were independent prognostic factors for survival and recurrence by multivariate analysis. CONCLUSIONS: No significant differences were seen in outcomes by lesion side in patients receiving curative surgery for Bismuth type III hilar cholangiocarcinoma.

Zinc-mediated Reversible Multimerization of Hsp31 Enhances the Activity of Holding Chaperone.

Hsp31 protein, belonging to the DJ-1/ThiJ/PfpI superfamily, increases the survival of Escherichia coli under various stresses. While it was reported as a holding chaperone, Hsp31 was also shown to exhibit the glyoxalase III activity in subsequent study. Here, we describe our finding that Hsp31 undergoes a Zn+2-mediated multimerization (HMWZinc), resulting in an enhanced chaperone activity. Furthermore, it was shown that the formation of HMWZinc is reversible such that the oligomer dissociates into the native dimer by EDTA incubation. We attempted to determine the structural change involving the transition between the native dimer and HMWZinc by adding Ni+2, which is Zn+2-mimetic, producing a potential intermediate structure. An analysis of this intermediate revealed a structure with hydrophobic interior exposed, due to an unfolding of the N-terminal loop and the C-terminal ß-to-α region. A treatment with hydrogen peroxide accelerated HMWZinc formation, so that the Hsp31C185E mutant rendered the formation of HMWZinc even at 45 °C. However, the presence of Zn+2 in the catalytic site antagonizes the oxidation of C185, implying a negative role. Our results suggest an unprecedented mechanism of the enhancing chaperone activity by Hsp31, in which the reversible formation of HMWZinc occurs in the presence of heat and Zn+2 ion.

Backbone resonance assignments of the Escherichia coli 62 kDa protein, Hsp31.

Dimeric Hsp31 protein was first characterized as a holding chaperone of Escherichia coli (E. coli), and has been suggested as having protease activity due to the presence of a potential catalytic triad, Cys185, His186, and Asp214. However, it has recently been reported that Hsp31 displays a relatively strong glyoxalase III activity that can decompose reactive carbonyl species (methylglyoxal and glyoxal) in the absence of additional cofactor. Hsp31 is a representative member of the DJ-1/ThiJ/PfpI protein superfamily, and the importance of DJ-1 protein in Parkinson's disease has been well known. The structural flexibility of the long loop region, which encompasses from the P- to the A-domain, is important for the chaperone activity of Hsp31. The backbone chemical shifts (CSs) would be useful for studying the structural changes of Hsp31 that are critical for the holding chaperone activity, and also for deciphering the switching mechanism between the glyoxalase III and the chaperone. Here, we report the backbone CSs (HN, N, CO, Cα, and Cß) of the deuterated Hsp31 protein (62 kDa). The CS analysis showed that the predicted regions of secondary structures are in good agreement with those observed in the previous crystal structure of Hsp31.

Three-dimensional image transmission and reconstruction for multisensor imaging system using interleaver division multiple access.

In this paper, we present an optical image transmission and reconstruction system of 3D objects using a multisensor imaging system and interleaver division multiple access (IDMA) channel. When the 3D image data from the multisensor imaging system are transmitted over a wireless channel, loss or distortion of original data may occur by wireless channel environment, such as multiple access interference and channel noise. To solve this problem, an optical 3D image reconstruction scheme and IDMA technique can be used. Reconstructed 3D image data at the receiver is clear enough to distinguish the depth of 3D objects. To prove our proposed scheme, we carry out an optical experiment for sensing 3D information and simulation for data transmission of a multisensor imaging system via IDMA with channel noise.

Stereospecific mechanism of DJ-1 glyoxalases inferred from their hemithioacetal-containing crystal structures.

UNLABELLED: DJ-1 family proteins have recently been characterized as novel glyoxalases, although their cofactor-free catalytic mechanisms are not fully understood. Here, we obtained crystals of Arabidopsis thaliana DJ-1d (atDJ-1d) and Homo sapiens DJ-1 (hDJ-1) covalently bound to glyoxylate, an analog of methylglyoxal, forming a hemithioacetal that presumably mimics an intermediate structure in catalysis of methylglyoxal to lactate. The deuteration level of lactate supported the proton transfer mechanism in the enzyme reaction. Differences in the enantiomeric specificity of d/l-lactacte formation observed for the DJ-1 superfamily proteins are explained by the presence of a His residue in the active site with essential Cys and Glu residues. The model for the stereospecificity was further evaluated by a molecular modeling simulation with methylglyoxal hemithioacetal superimposed on the glyoxylate hemithioacetal. The mechanism of DJ-1 glyoxalase provides a basis for understanding the His residue-based stereospecificity. DATABASE: Structural data have been submitted to the Protein Data Bank under accession numbers 4OFW (structure of atDJ-1d), 4OGF (structure of hDJ-1 with glyoxylate) and 4OGG (structure of atDJ-1d with glyoxylate).

Pathologic T1 subclassification of ampullary carcinoma with perisphincteric or duodenal submucosal invasion: Is it T1b?

CONTEXT: In ampullary carcinoma staging, T1 is defined as a tumor limited to the ampulla of Vater or the sphincter of Oddi, and T2 is defined as invasion into the duodenal wall. However, the definition of duodenal wall invasion is vague. Ampullary carcinoma that invades beyond the sphincteric of Oddi (perisphincteric invasion) or into the duodenal submucosa could be considered pT1b because submucosal invasion is classified as pT1b in gastrointestinal tract tumors. However, there are no data regarding T subclassifications for ampullary carcinoma with perisphincteric or duodenal submucosa invasion. OBJECTIVE: To determine the T subclassification of ampullary carcinoma that invades into perisphincteric or duodenal submucosa. DESIGN: Pathologically proven ampullary carcinomas with T1 or T2 were reviewed (n = 105). We reclassified tumors as pT1a that were limited to within the sphincter of Oddi (n = 40; 38%), as pT1b for tumors that invaded beyond the sphincter of Oddi or into the duodenal submucosa (n = 25; 24%), and as pT2 for tumors that invaded into duodenal proper muscle (n = 40; 38%). RESULTS: Lymph node metastasis and recurrence were absent in ampullary carcinoma with pT1a, whereas nodal metastasis were noted in 24% (6 of 25) and 40% (16 of 40) of the ampullary carcinomas with pT1b and pT2, respectively. Tumor recurrence/metastasis rate of ampullary carcinoma with pT1b and pT2 was 44% (11 of 25) and 40% (16 of 40), respectively. The 5-year disease-free-survival rates from ampullary carcinoma with pT1a, pT1b, and pT2 were 95% (38 of 40), 56% (14 of 25), and 58% (23 of 40), respectively (P = .003). The 5-year overall survival from ampullary carcinoma with pT1a, pT1b, and pT2 was 98% (39 of 40), 72% (18 of 25), and 60% (24 of 40), respectively. CONCLUSIONS: The clinicopathologic outcome of ampullary carcinoma with a pT1b subclassification was worse than it was for T1a and approached the outcome for pT2.

Glucagon/insulin ratio in preoperative screening before pancreatic surgery: correlation with hemoglobin A1C in subjects with and without pancreatic cancer.

Role of impaired suppression of glucagon secretion in the pathogenesis of pancreatic cancer-associated diabetes has been suggested. We examined the correlation between glucagon/insulin ratio (G/I) after glucose challenge and hemoglobin A1C (A1C) in subjects with and without pancreatic cancer. Data were gathered from a preoperative screening 75-g oral glucose tolerance test in patients who would eventually undergo pancreatic resection. A multiple linear regression analysis was conducted using the following covariates: age, body mass index, hemoglobin, glucose and insulin levels at the corresponding time points, indices of insulin resistance, duration of diabetes, insulinogenic index, and use of glucose-lowering drugs. In subject group with pancreatic cancer (n = 45), but not in subject group without pancreatic cancer (n = 101), participants with A1C ≥ 6.5 % had significantly higher glucagon levels, lower insulin levels, and higher G/I ratios after the glucose challenge than those of the subjects with A1C <5.7 %. In the multiple linear regression analysis, there was an independent correlation between post-challenge G/I ratio and A1C in both groups. Some of the patients without pancreatic cancer had inappropriately elevated G/I ratios despite A1C <6.5 %. These patients were characterized by lower insulinogenic indices (p = 0.004) and less insulin resistance (p = 0.008). In conclusion, post-challenge G/I ratio independently correlated with A1C in patients with pancreatic cancer. Although significant, the degree of correlation was weakened in the subjects without pancreatic cancer because some had lower insulin secretory reserve compensated by less insulin resistance, resulting in inappropriately elevated G/I ratios relative to A1C.

Novel glyoxalases from Arabidopsis thaliana.

We examined six Arabidopsis thaliana genes from the DJ-1/PfpI superfamily for similarity to the recently characterized bacterial and animal glyoxalases. Based on their sequence similarities, the six genes were classified into two sub-groups consisting of homologs of the human DJ-1 gene and the PH1704 gene of Pyrococcus horikoshii. Unlike the homologs from other species, all the A. thaliana genes have two tandem domains, which may have been created by gene duplication. The six AtDJ-1 proteins (a-f) were expressed in Escherichia coli for enzymatic assays with glyoxals. The DJ-1d protein, which belongs to the PH1704 sub-group, exhibits the highest activity against methylglyoxal and glyoxal, and K(m) values of 0.10 and 0.27 mm were measured for these two substrates, respectively, while the corresponding k(cat) values were 1700 and 2200 min(-1), respectively. The DJ-1a and DJ-1b glyoxalases exhibited higher specificity towards glyoxal. The other three proteins have either no or extremely low activity for glyoxals. For the DJ-1d enzyme, the residues, Cys120/313 and Glu19/212 at the active site and His121/314 and Glu94/287 at the oligomeric interface were mutated to alanines. As in other enzymes characterized to date, mutation of either the Cys or the Glu residues of the active site completely abolished enzyme activity, whereas mutation of the interface residues produced a variable decrease in activity. DJ-1d differs from its animal and bacterial homologs with respect to the configuration of its catalytic residues and the oligomeric property of the enzyme. When the wild-type DJ-1d enzyme was expressed in E. coli, the bacteria became resistant to glyoxals.

Structural alteration of Escherichia coli Hsp31 by thermal unfolding increases chaperone activity.

Escherichia coli Hsp31, encoded by hchA, is a heat-inducible molecular chaperone. We found that Hsp31 undergoes a conformational change via temperature-induced unfolding, generating a high molecular weight (HMW) form with enhanced chaperone activity. Although it has previously been reported that some subunits of the Hsp31 crystal structure show structural heterogeneity with increased hydrophobic surfaces, Hsp31 basically forms a dimer. We found that a C-terminal deletion (CΔ19) of Hsp31 exhibited structurally and functionally similar characteristics to that of the HMW form. Both the CΔ19 and HMW forms achieved a structure with considerably more ß-sheets and less α-helices than the native dimeric form, exposing a portion of its hydrophobic surfaces. The structural alterations were determined from its spectral changes in circular dichroism, intrinsic fluorescence of tryptophan residues, and fluorescence of bis-ANS binding to a hydrophobic surface. Interestingly, during thermal transition, the dimeric Hsp31 undergoes a conformational change to the HMW species via the CΔ19 structure, as monitored with near-UV CD spectrum, implying that the CΔ19 resembles an intermediate state between the dimer and the HMW form. From these results, we propose that Hsp31 transforms itself into a fully functional chaperone by altering its tertiary and quaternary structures.

Long-term effects of pancreaticoduodenectomy on glucose metabolism.

BACKGROUND: To analyse the association between pancreatogenic diabetes and the volume of the remnant pancreas after pancreaticoduodenectomy and to identify clinicopathologic factors correlated with pancreatogenic diabetes. METHODS: Among the patients who underwent pancreaticoduodenenctomy from 2003 to 2004, 55 patients who survived by 2009 and were able to measure the volume of the pancreas pre- and post-operatively by CT volumetry were included in this study. Twelve patients had diabetes before surgery. Median follow-up duration was 55.2 and 67.3 months for CT volumetry, pancreatogenic diabetes, respectively. RESULTS: Among 43 patients without preoperative diabetes, nine patients (21%) developed newly diabetes after surgery. Among 12 patients with diabetes, 10 patients had worsened glucose control. The immediate post-operative Vol% was 46.5% and the last Vol% was 31.5% (P < 0.001). Preoperative diabetes, malignant pathology, absence of post-operative pancreatic fistula, chemotherapy and radiotherapy were correlated with a lower Vol%. Atrophic changes were observed in 29 patients and hypertrophic changes in 13 patients. Comparative analysis according to the change in the Vol% revealed no differences in the clinicopathological factors associated with new-onset pancreatogenic diabetes or aggravation of preoperative diabetes. CONCLUSIONS: While some patients had a hypertrophic pancreas at the last follow-up, which reflected the capacity for pancreatic regeneration and some factors were associated with a lower volume of the remnant pancreas, the volume of the remnant pancreas seem not to be associated with pancreatogenic diabetes. There were no clinicopathologic factors identified associated with the risk for pancreatogenic diabetes.

Ablation of Rassf2 induces bone defects and subsequent haematopoietic anomalies in mice.

RASSF2 belongs to the Ras-association domain family (RASSF) of proteins, which may be involved in the Hippo signalling pathway. However, the role of RASSF2 in vivo is unknown. Here, we show that Rassf2 knockout mice manifest a multisystemic phenotype including haematopoietic anomalies and defects in bone remodelling. Bone marrow (BM) transplantation showed that Rassf2(-/-) BM cells had a normal haematopoietic reconstitution activity, indicating no intrinsic haematopoietic defects. Notably, in vitro differentiation studies revealed that ablation of Rassf2 suppressed osteoblastogenesis but promoted osteoclastogenesis. Co-culture experiments showed that an intrinsic defect in osteoblast differentiation from Rassf2(-/-) osteoblast precursors likely leads to both haematopoiesis and osteoclast defects in Rassf2(-/-) mice. Moreover, Rassf2 deficiency resulted in hyperactivation of nuclear factor (NF)-κB during both osteoclast and osteoblast differentiation. RASSF2 associated with IκB kinase (IKK) α and ß forms, and suppressed IKK activity. Introduction of either RASSF2 or a dominant-negative form of IKK into Rassf2(-/-) osteoclast or osteoblast precursors inhibited NF-κB hyperactivation and normalized osteoclast and osteoblast differentiation. These observations indicate that RASSF2 regulates osteoblast and osteoclast differentiation by inhibiting NF-κB signalling.

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas.

AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P=0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P=0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (P<0.001) and tumors without metastasis (P=0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease.

Hsp31 of Escherichia coli K-12 is glyoxalase III.

Hsp31 encoded by hchA is known as a heat-inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp-214, His-186 and Cys-185, its enzymatic function, besides weak amino-peptidase activity, is still unknown. We found that Hsp31 displays glyoxalase activity that catalyses the conversion of methylglyoxal (MG) to d-lactate without an additional cofactor. The glyoxalase activity was completely abolished in the hchA-deficient strain, confirming the relationship between the hchA gene and its enzymatic activity in vivo. Hsp31 exhibits Michaelis-Menten kinetics for substrates MG with K(m) and k(cat) of 1.43±0.12 mM and 156.9±5.5 min⁻¹ respectively. The highest glyoxalase activity was found at 35-40 °C and pH of 6.0-8.0, and the activity was significantly inhibited by Cu²âº, Fe³âº and Zn²âº. Mutagenesis studies based on our evaluation of conserved catalytic residues revealed that the Cys-185 and Glu-77 were essential for catalysis, whereas His-186 was less crucial for enzymatic function, although it participates in the catalytic process. The stationary-phase Escherichia coli cells became more susceptible to MG when hchA was deleted, which was complemented by an expression of plasmid-encoded hchA. Furthermore, an accumulation of intracellular MG was observed in hchA-deficient strains.

Male-like sexual behavior of female mouse lacking fucose mutarotase.

BACKGROUND: Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated. RESULTS: We generated a mutant mouse specifically lacking the fucose mutarotase (FucM) gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv) of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP) in a mutant embryo relative to that of a wild-type embryo. CONCLUSIONS: The observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.

Carcinoma of the middle bile duct: is bile duct segmental resection appropriate?

AIM: To compare survival between bile duct segmental resection (BDSR) and pancreaticoduodenectomy (PD) for treating distal bile duct cancers. METHODS: Retrospective analysis was conducted for 45 patients in a BDSR group and for 149 patients in a PD group. RESULTS: The T-stage (P < 0.001), lymph node invasion (P = 0.010) and tumor differentiation (P = 0.005) were significant prognostic factors in the BDSR group. The 3- and 5-year overall survival rates for the BDSR group and PD group were 51.7% and 36.6%, respectively and 46.0% and 38.1%, respectively (P = 0.099). The BDSR group and PD group did not show any significant difference in survival when this was adjusted for the TNM stage. The 3- and 5-year survival rates were: stage Ia [BDSR (100.0% and 100.0%) vs PD (76.9% and 68.4%) (P = 0.226)]; stage Ib [BDSR (55.8% and 32.6%) vs PD (59.3% and 59.3%) (P = 0.942)]; stage IIb [BDSR (19.2% and 19.2%) vs PD (31.9% and 14.2%) (P = 0.669)]. CONCLUSION: BDSR can be justified as an alternative radical operation for patients with middle bile duct in selected patients with no adjacent organ invasion and resection margin is negative.

Comparison of different pancreatic anastomosis techniques using the definitions of the International Study Group of Pancreatic Surgery: a single surgeon's experience.

OBJECTIVES: We aimed to compare different techniques using the definitions of the International Study Group of Pancreatic Surgery for postoperative complications after pancreaticoduodenectomy. METHODS: The perioperative data of 119 patients that underwent pancreaticoduodenectomy by a single surgeon were retrospectively analyzed. Pancreaticojejunal anastomosis was performed using the dunking method (n = 39), the duct-to-mucosa anastomosis method (n = 40), and the duct-to-mucosa adaptation (n = 40). RESULTS: The most frequent complication was postoperative pancreatic fistula (POPF; grades A, 21%; B, 8%; and C, 3%), postpancreatectomy hemorrhage (PPH; grades B, 7% and C, 1%), and delayed gastric emptying (DGE; grades A, 1% and B, 6%). No significant differences in POPF were found between patients who underwent different types of pancreatic anastomoses. Only pancreatic ductal adenocarcinoma (P = 0.001) and pancreatic texture (P = 0.012) were potentially related to POPF. Patients with or without POPF grade A had shorter postoperative stays than patients with grade B or C POPF (P < 0.001), and similar findings were obtained for DGE and PPH. CONCLUSIONS: The successful management of pancreatic anastomoses depends more on a meticulous surgical technique and appropriate experience rather than on the type of technique. Furthermore, the International Study Group of Pancreatic Surgery definitions of POPF, DGE, and PPH seem objective and universally acceptable.

Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients.

The purpose of this study was to evaluate the effects of autologous islet transplantation (ITx) on glucose homeostasis and insulin secretory function after partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx controls were recruited, and all groups were followed over a 24-month period. They performed the 75-g oral glucose tolerance test and the 1-mg glucagon stimulation test. Hemoglobin A(1c) was measured, and indices of insulin secretion were calculated. In the Px + ITx group, insulin secretion increased after a nadir at 6 months. Glucose tolerance, which had been abruptly impaired immediately after Px, recovered until 6 months and stabilized thereafter. As a result, differences in glucose intolerance emerged between the subjects in the Px group and those in the Px + ITx group at 24 months after Px. Characteristic variables in the better insulin secretory subjects in the Px + ITx group included younger age, less extensive pancreas resection, and a greater number of total islets. In summary, delayed amelioration of glucose intolerance was induced by autologous ITx after partial Px, even with a small number of islets.