Transient Microstructure Evolutions and Local Properties of Dual-Phase 980 MPa Grade Steel Via Friction Stir Spot Processing.

Friction stir processing is a novel solid-state process to modify microstructures and their properties by intense, localized plastic deformation. However, little research has been reported for microstructure evolutions of advanced high-strength steels during the process. The present work focuses on the study of transient microstructure changes and local mechanical properties for friction stir spot processed dual-phase (DP) 980 MPa grade steel (DP980) under different peak temperatures. A pinless silicon nitride ceramic tool was used to produce relatively simple material deformation and flow near the tool. Friction stir spot processed steel samples were characterized by optical and electron microscopies. Furthermore, Vickers microhardness and nano-indentation measurements were used to study local mechanical properties for correlation with microstructures. A swallow layer of refined grains (<0.6 µm) was obtained with a low peak temperature (under 400 °C), whereas higher peak temperatures (>Ac1) led to a change in grain size with different microstructures (fine-grained DP or martensite). Electron back-scattered diffraction characterizations revealed a large deformation in the as-received microstructures (mixture of ferrite and tempered martensite) induced by friction stir spot processing, leading to recrystallization and grain refinement around the stirred zone. Also, nano-indentation measurements showed a higher hardness than the hardness of the as-received DP980. Friction stir processing with different process conditions effectively changed microstructures and local mechanical properties.

Prophylactic drain management after pancreaticoduodenectomy without focusing on the drain fluid amylase level: A prospective validation study regarding criteria for early drain removal that do not include the drain fluid amylase level.

BACKGROUND/PURPOSE: Early drain removal (EDR) based on drain fluid amylase level (DFA) after pancreaticoduodenectomy excluded 15%-40% patients from EDR because of inappropriate DFA. METHODS: Of 198 pancreatoduodenectomy cases, we used the first 105 cases as an exploration cohort to construct the optimal criteria for EDR on postoperative day (POD)4 that were applied to the subsequent 93 cases used as the validation cohort. After that, we examined another 142 patients to further assess the efficacy of the new EDR criteria. RESULTS: Of the four independent predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) ([1] soft pancreas, [2] positive drain fluid culture on POD1, and [3] serum C-reactive protein [CRP] ≥13 mg/dL on POD4) in the exploration cohort, EDR was applied to cases in the validation cohort meeting the [2] and/or [3], enabling 96% (89/93) applicability of EDR. Outcomes were improved in the validation cohort compared to the exploration cohort; CR-POPF: 8.6% vs 25.7%, P = .005; Dindo-Clavien grade ≥ 3 complications: 23.7% vs 41.9%, P = .007; and median hospital stay (day): 21 vs 27, P = .005. The subsequent 142 patients showed 92% (131/142) applicability of EDR and 5.6% (8/142) incidence of CR-POPF. CONCLUSIONS: Our new criteria for EDR, without DFA, enabled ≥ 90% applicability of EDR and reduced CR-POPF.

Efficacy of prolonged elemental diet therapy after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: A pilot prospective randomized trial (UMIN000004108).

BACKGROUNDS AND AIMS: This randomized clinical trial examined efficacy of prolonged elemental diet (ED) therapy after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), which often causes postoperative malnutrition leading to worsened short- and long-term outcomes. METHODS: Thirty-nine patients with PDAC receiving PD was randomly assigned to prolonged ED group (PEDG) and control group (CG). Fat-free ED (Elental®, EA Pharma CO., Ltd., Tokyo, Japan) via tube jejunostomy was initiated on postoperative day 1 and increased to maintain with 600 kcal/day in addition to oral intake. ED was discontinued if sufficient oral intake was achieved in CG but continued during 3 postoperative months in PEDG. Primary outcome was complication necessitating readmission. Secondary outcomes were nutritional parameters, relative dose intensity (RDI) in cases of adjuvant chemotherapy, and survival outcomes. RESULTS: Twenty patients were assigned to CG and 19 to PEDG. Cumulative post-discharge readmission rate was significantly lower in PEDG than in CG (PEDG vs CG; 12.6% vs 43.7% at 12-post-discharge-month; p = 0.018). Total calorie and ED-derived protein intakes were significantly larger in PEDG than in CG up to 3-postoperative-month but thereafter similar among groups. Lymphocyte counts were significantly increased and neutrophil-to-lymphocyte-ratio (NLR) was significantly reduced in PEDG than in CG at 2-, 3-, and 6-postoperative-month. However, other outcome measures did not differ among groups. CONCLUSION: This trial failed to show survival benefit of prolonged ED therapy but demonstrated its favorable effect on increased lymphocyte counts, reduced NLR, and prevention of complications necessitating readmission, those which may lead to survival benefit with some modifications.

Single-institution experience with gemcitabine-cisplatin combination therapy as a second-line treatment for patients with unresectable biliary tract cancer after failure of gemcitabine-S-1 combination therapy: a prospective feasibility study.

BACKGROUND: NCCN and Japanese clinical guidelines for the treatment of biliary tract cancer (BTC) addressed gemcitabine-cisplatin combination (GC) as first-line chemotherapy for patients with advanced BTC ineligible for surgery in 2013. However, gemcitabine-S1 combination therapy (GS) has been widely used as first-line treatment in Japan because Japanese social insurance coverage of S-1 for BTC was approved prior to that of cisplatin. AIM: To elucidate the efficacy and tolerability of GC as second-line chemotherapy for patients with unresectable BTC after failure of GS. PATIENTS AND METHODS: Between September 2008 and August 2011, patients with unresectable BTC who provided informed consent and received GC comprising gemcitabine at 1000 mg/m2 and cisplatin at 20 mg/m2 given on days 1 and 8 in a 3-week cycle after failure of GS were included in the present study. Clinical data from these patients were collected prospectively. Primary endpoints were overall survival and time to progression (TTP). Secondary endpoints were response and tolerability. RESULTS: Twenty-seven patients were analyzed. Median survival time (MST) and TTP from the beginning of second-line treatment were 6.5 and 3.3 months, respectively, whereas MST from the commencement of first-line therapy was 12.06 months. One patient showed partial response, 16 had stable disease and 10 experienced disease progression. As a result, disease control rate was 63.0%. In total, 119 courses (median, 4; range, 1-15) were administered. Discontinuation of GC due to drug toxicities was not observed. CONCLUSION: Although some issues remain to be clarified, mainly due to the small sample size, this single-institution experience with GC as second-line treatment after failure of GS showed acceptable outcomes and good tolerability.

Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer.

BACKGROUND: Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC). MATERIALS AND METHODS: Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed. RESULTS: In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002). CONCLUSION: Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT.

Endoscopic inside stent placement is suitable as a bridging treatment for preoperative biliary tract cancer.

BACKGROUND: Endoscopic biliary stenting (EBS) is one of the most important palliative treatments for biliary tract cancer. However, reflux cholangitis arising from bacterial adherence to the inner wall of the stent must be avoided. We evaluated the use of EBS above the sphincter of Oddi to determine whether reflux cholangitis could be prevented in preoperative cases. METHODS: Fifty-seven patients with primary biliary tract cancer were retrospectively recruited for the evaluation of stent placement either above (n = 25; inside stent group) or across (n = 32; conventional stent group) the sphincter of Oddi. We compared the stent patency periods prior to the time of surgical resection. RESULTS: The preoperative periods were 96.3 days in the conventional stent group and 96.8 days in the inside stent group (P = 0.979). Obstructive jaundice and/or acute cholangitis occurred in 7 patients (28.0%) in the inside stent group and in 15 patients (46.9%) in the conventional stent group during the preoperative period (P = 0.150). The average patency periods of the stents were 85.2 days (range, 13-387 days) for the inside stent group and 49.1 days (range, 9-136 days) for the conventional stent group (log-rank test: P = 0.009). The mean numbers of re-interventions because of stent occlusion were 0.32 for the inside stent group and 1.03 for the conventional stent group (P = 0.026). Post-endoscopic retrograde cholangiopancreatography complications occurred in 2 patients in the inside stent group and 4 patients in the conventional stent group (P = 0.516). Postoperative liver abscess occurred in 1 patient in the inside stent group and 5 patients in the conventional stent group (P = 0.968). Inside stent placement was the only significant preventative factor associated with stent obstruction based on univariate (hazard ratio [HR], 0.286; 95% confidence interval [CI], 0.114-0.719; P = 0.008) and multivariate (HR, 0.292; 95% CI, 0.114-0.750; P = 0.011) analyses. CONCLUSION: Temporary plastic stent placement above the sphincter of Oddi is a better bridging treatment than conventional stent placement in preoperative primary biliary tract cancer.

Stroke Volume Variation for the Evaluation of Circulating Blood Volume after Living Donor Liver Transplantation.

BACKGROUND/AIMS: Stroke volume variation (SVV) is a sensitive, functional preload index for evaluating responsiveness to volume loading in patients during liver transplantation (LT). However, there have been few reports concerning the experience of using SVV after LT. METHODOLOGY: Of 61 patients who underwent living donor LT (LDLT) at our institute, we used only central venous pressure (CVP) to guide fluid management in the first 52 patients (conventional group) and used both SVV and CVP in the next 9 patients (SVV group). The boundary values used for fluid management were 10mmHg for CVP and 10% for SVV. Changes in SVV and CVP were compared. RESULTS: In the SVV group, SVV was less than 10% in all patients when the diuretic phase appeared. However, CVP was more than 10mmHg in only 4 cases (44.4%). Between surgery and the removal of endotracheal tubes, the lowest the ratio between arterial oxygen tension and fractional inspired oxygen (PaO2/FiO2 ratio) in the SVV group (290.7 ± 100.5) was significantly higher than that in the conventional group (205.6 ± 98.9, P = 0.017). CONCLUSION: Postoperative fluid management using SVV may be especially useful after LDLT. Monitoring the circulating blood volume using a 10% SVV index is useful for avoiding lung edema after LT.

Thrombomodulin improves rat survival after extensive hepatectomy.

BACKGROUND: Recombinant human soluble thrombomodulin (rTM) protects against disseminated intravascular coagulopathy by inhibiting coagulation, inflammation, and apoptosis. This study tests the hypothesis that rTM is hepatoprotective after extensive hepatectomy (Hx) and investigates the mechanisms underlying this effect. MATERIALS AND METHODS: Experiment 1: rats (15 per group) were injected with rTM (1.0 or 2.0 mg/kg) or saline just before 95% Hx and their 7-d survival assessed. Experiment 2: rats were assigned to either a treated (2.0 mg/kg rTM just before Hx) or control group (n = 5 per group). Five rats per group were euthanized immediately after surgery, and at 1, 3, 6, 12, and 24 h postoperatively; serum and liver remnant samples were collected for biochemical and histologic analysis, as well as reverse-transcription polymerase chain reaction and Western blotting. RESULTS: All saline-injected rats died within 52 h of Hx, whereas injection of 2.0 mg/kg rTM prolonged survival (P = 0.003). rTM increased the number of Ki67-positive cells and reduced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. The number of myeloperoxidase-positive cells and the expression of high-mobility group box 1 protein did not differ. Reverse-transcription polymerase chain reaction revealed that rTM significantly enhanced protease-activated receptor-1 and sphingosine kinase 1 messenger RNA expression and significantly reduced plasminogen activator inhibitor-1 and Bax messenger RNA expression. Immunohistochemistry and Western blotting demonstrated that protease-activated receptor-1 expression 24 h after Hx was significantly higher in rTM-treated than in control rats. CONCLUSIONS: rTM may improve survival after extensive Hx by inhibiting apoptosis and promoting liver regeneration.

[Surgical strategies for middle and lower bile duct cancer].

R0 resectability is thought to be one of the important prognostic factors in bile duct cancer. To achieve R0 resection, accurate preoperative diagnosis is essential. However, intraoperative frozen-section diagnosis sometimes reveals positive ductal margins. It is known that nodular infiltrative tumors tend to extend to the subserosal layer. On the other hand, papillary tumors often have extensive intramural extension, the so-called intraepithelial spread. This type of extension remains difficult to diagnose preoperatively. Some investigators query the clinical significance of positive ductal margins with carcinoma in situ or severe dysplasia. However, even in such instances, local recurrence 5 years after the initial surgery was reported in several articles. Middle bile duct cancer often extends to the upper (hilar bile duct) and lower (intrapancreatic bile duct) sections of the bile duct. To achieve R0 resection, a variety of operative procedures should be considered. For example, hepatopancreatoduodenectomy is required in patients with broad tumor extension up to the hilar bile ducts. However, hilar bile duct resection can result in R0 resection for patients with limited tumor extension. Thus, appropriate operative procedures should be selected based on patients' organ function and other possible prognostic factors, such as lymph node metastases.

[A case of post-operative recurrence of pancreatic cancer in the residual pancreas treated by resection of the residual pancreas following radiological complete response achieved with second-line FOLFIRINOX].

A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1 combined with gemcitabine was conducted. But one year later, a recurrent tumor was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial response, and after 9 courses, a radiological complete response was achieved. We could then perform total pancreatotectomy and resection of the metastatic liver tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be considered.

Imaging and surgical planning for perihilar cholangiocarcinoma.

Recent advances in multidetector computed tomography (MDCT) offer several benefits for management of perihilar tumors. Resection planning for perihilar cholangiocarcinoma should consider two factors: safety and curability. Recognition of individual anatomic variations is particularly important for avoiding intraoperative injury. In particular, hepatic arterial variations often restrict resection procedures. Extent of both longitudinal and vertical invasion by biliary tumors can be estimated from multiplanar reconstruction (MPR) images. Longitudinal extent of resection can be planned based on two anatomic landmarks, the U point and the P point, readily identifiable in preoperative 3-dimensional (3D) images and by intraoperative inspection. Concerning vertical invasion, when direct vascular invasion is suspected from a finding of attachment of tumor and vessels such as portal veins and/or hepatic arteries without a thin low-density plane of separation shown by MPR, these vessels should be resected en bloc with the tumor. Surgical team members can plan and simulate details of vascular resection and reconstruction using 3D images. Reduced operative morbidity and increased R0 resection rates are expected because of better planning of procedures. These techniques soon may increase long-term survival for patients with perihilar cholangiocarcinoma.

Immunological impact of neoadjuvant chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Little is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer. METHODS: Fifty-two patients with pancreatic cancer who underwent surgical resection were enrolled in this study. NACRT was administered to 22 patients, whereas the other 30 patients underwent surgical resection without NACRT. The resected tumor specimens were analyzed for the presence of tumor-infiltrating lymphocytes by using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major histocompatibility complex class I (MHC class I) antigen. RESULTS: The number of CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT than in those who did not receive NACRT. No significant difference in MHC class I expression was observed between the groups. In the NACRT group, patients with a high accumulation of CD8+ cells experienced longer overall survival than those with a low number of CD8+ cells. CONCLUSIONS: NACRT may induce the accumulation of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of CD8+ cells might be a good prognostic marker for pancreatic cancer treated with NACRT.

Covered self-expandable metal stent deployment promises safe neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic head cancer.

BACKGROUND: Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period. PATIENTS AND METHODS: We reviewed the outcomes of patients with BRPHC, then divided them chronologically into three groups as follows. Group A: upfront surgery with plastic stent (PS) deployment; group B: PS deployment plus neoadjuvant chemotherapy (NAC) and/or NACRT; group C: CSEMS deployment plus NAC/NACRT. Patients were categorized as borderline resectable based on National Comprehensive Cancer Network Guidelines, 2010. Days to reintervention (DR), reintervention rate, and the rate of R0 and complications were studied. Safe margin-negative resection (R0) surgery was defined as R0 surgery without reintervention during the NACRT period and no postoperative complications. RESULTS: DR were as follows. Groups A, B and C were 32, 55 and 97 days, respectively (P < 0.05). R0 surgery obtained in groups A, B and C was 53% (9/17), 100% (17/17) and 93% (14/15), respectively. CSEMS did not interfere with surgery. Safe R0 surgery obtained in groups B and C was 11% (2/19) and 67% (10/15), respectively (P < 0.05). Multivariate analysis showed that the odds ratio for safe R0 surgery was 16.210 (95% CI 2.457-106.962, P = 0.003) for CSEMS placement. CONCLUSION: CSEMS should be considered to relieve symptomatic biliary obstruction in patients with BRPHC receiving NACRT in view of the high attainability rate of safe R0 surgery compared to that with PS deployment.

Severity and prognostic assessment of the endotoxin activity assay in biliary tract infection.

BACKGROUND: Acute cholangitis and cholecystitis (AC) often progress to severe septic conditions. We evaluated the endotoxin activity assay (EAA) for assessment and prediction of the severity of AC. METHODS: We retrospectively reviewed 98 patients diagnosed with AC. We divided them into low (<0.4) and high (≥0.4) groups based on EAA values. RESULTS: Endotoxin levels showed no correlation with EAA values. Serum C-reactive protein (8.57 vs. 5.23 mg/dl, P = 0.02), procalcitonin (2.45 vs. 0.48 ng/ml, P = 0.004), and the positive culture rate of blood (50% vs. 15%, P < 0.001) were significantly higher in the high group than in the low group. Platelet counts were significantly lower in the high group than in the low group (23.9 vs. 13.5 10(4) /ml, P = 0.004). The ratio of patients with a Japanese Association for Acute Medicine disseminated intravascular coagulation score ≥4 (32% vs. 14%, P = 0.032) was significantly higher in the high group than in the low group. There was a significantly higher percentage of patients with a severe grade of AC in the high group than patients with a mild or moderate grade (32% vs. 15%, P = 0.05). CONCLUSIONS: Endotoxin activity assay is useful for assessment and early prediction of septic conditions due to AC.

Solitary rib recurrence of hilar cholangiocarcinoma 10 years after resection: report of a case.

A 61-year-old female underwent right hemihepatectomy and caudate lobectomy for hilar cholangiocarcinoma in 1999. Ten years later, increasing serum carbohydrate 19-9 was detected by routine follow-up. Subsequent positron emission tomography revealed an asymptomatic lesion in the right 11th rib. As the mass steadily grew in size, the lesion was resected en bloc with the affected rib and muscle. The histopathological findings closely resembled those of the primary cholangiocarcinoma. Thus, the tumor was diagnosed as a metastatic recurrence 10 years after resection of the primary tumor. There have been a few reports of cholangiocarcinoma recurrence in long-term survivors at the surgical margins, peritoneum, or transhepatic drainage route. However, there are no reports of solitary extra-abdominal recurrence. This case highlights the need for careful follow-up of patients with cholangiocarcinoma and nodal metastasis, even in the absence of recurrence for >5 years after curative resection.

Septic pulmonary embolism originated from subcutaneous abscess after living donor liver transplantation: a pitfall of postoperative management.

The use of immunosuppressants after liver transplantation (LT) is associated with postoperative complications, including infections. A 49-year-old male underwent living-donor (LD) LT because of primary sclerosing cholangitis. He was treated with tacrolimus, mycophenolate mofetil, and steroids as immunosuppressants, discharged on postoperative day (POD) 40, and re-admitted because of severe acute cellular rejection on POD 48. Three courses of steroid pulse therapy were performed, and continuous peripheral intravenous drip infusion therapy via the left forearm was necessary for 20 days because of appetite loss. The patient was discharged on POD 83, but re-admitted on POD 87 with pyrexia. A subcutaneous abscess was present at a puncture wound on the left forearm formed by an intravenous drip during the last hospital stay. Furthermore, computed tomography showed five pieces of cavitary or wedge-shaped nodules in the bilateral lung. Because sputum revealed the presence of Gram-positive coccus, and subcutaneous abscess and blood cultures revealed Staphylococcus aureus, the pathogenesis was septic pulmonary embolism (SPE) secondary to S. aureus septicemia originating from a subcutaneous abscess formed by an intravenous drip. The patient was treated with drainage of the subcutaneous abscess and antibiotic therapy, and recovered immediately. Although there have been few reports of SPE after LDLT, SPE is fatal in up to 13.3 % of patients. Early diagnosis, drainage of the infectious source, and appropriate use of antimicrobial therapy should be necessary to overcome SPE. Furthermore, the identical intravenous catheters should be removed whenever possible to avoid infectious complications including SPE for patients who receive steroid pulse therapy after LDLT.

Surgical outcome and proposed strategy for biliary stricture after living donor liver transplantation: a single center analysis.

BACKGROUND/AIMS: To clarify the surgical outcome and propose an appropriate strategy for biliary stricture (BS) treatment after living donor liver transplantation (LDLT). METHODOLOGY: Among 53 patients who underwent LDLT at our institute, 45 patients had duct-to-duct anastomosis. Of these, 33 who survived for at least 12 months after LDLT comprised the study group. Clinical parameters, BS treatment outcomes, and predictive factors for long-term patency were investigated. RESULTS: Eleven patients developed BS. Biliary leakage occurred significantly more frequently, and the number of external biliary tubes was significantly lower than the number of graft bile-duct openings, in the BS group compared with the non-BS group (p=0.001 and 0.004). Multivariate analysis showed that the number of external biliary tubes was the only risk factor. Long-term patency was achieved in two patients in whom stents were retained for more than 20 months, which was significantly longer than in other patients (p=0.01). Identical stent-retention for more than 6 months was a risk factor for cholangitis. CONCLUSIONS: The number of external biliary tubes should match the number of graft bile-duct openings. When BS occurs, the duration of stent retention should be more than 20 months, and stents should be exchanged at least every 6 months.

Heart rate and blood pressure response to ramp exercise and exercise capacity in relation to age, gender, and mode of exercise in a healthy population.

BACKGROUND: The responses of heart rate (HR) and blood pressure to the ramp exercise test are not known and the current understanding of peak oxygen uptake and anaerobic threshold (AT) values in the normal Japanese population is insufficient. METHODS AND RESULTS: A total of 749 healthy Japanese subjects aged 20-78 years underwent a cardiopulmonary exercise test using a cycle ergometer or treadmill ergometer with ramp protocols. HR, systolic blood pressure (SBP), and oxygen uptake VO2 at rest, at AT, and at peak exercise were determined. HR and SBP at peak exercise in a cycle ergometer and treadmill ergometer test decreased with age. Work rate at peak exercise in a cycle ergometer increased with body weight and decreased with age. VO2 at AT and at peak exercise were higher in treadmill ergometer testing than in cycle ergometer testing, and were not affected by exercise protocol. Both of these decreased with age. CONCLUSIONS: The normal responses of HR and SBP to ramp exercise testing are reported for the first time. AT, peak VO2, and VO2 at each stage are shown for a healthy population. Some of these parameters were influenced by weight, gender, and age, as well as mode of exercise and the protocol used. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing.

Collapsin response mediator protein 4 expression is associated with liver metastasis and poor survival in pancreatic cancer.

BACKGROUND: Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer. METHODS: Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors. RESULTS: Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival. CONCLUSIONS: Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

Predictive factors for prolonged intubation following liver transplantation.

BACKGROUND/AIMS: This study identified risk factors associated with prolonged intubation after living donor liver transplantation (LDLT). METHODOLOGY: Out of 50 patients who underwent LDLT, clinical data were compared between those extubated within 4 days of LDLT (early group; n=20) and those extubated 5 days post-LDLT (delayed group; n=30). RESULTS: Univariate analysis associated the following factors with prolonged intubation: preoperative age >48 years (p=0.05), body mass index >22 kg/m² (p=0.01), creatinine clearance <90 mL/min/1.73 m² (p=0.003), ratio between arterial oxygen tension and fractional inspired oxygen ≤375 (p=0.02) and postoperative changes of body-weight per body surface area ((BW - preoperative BW)/BSA)) on postoperative day (POD) 3 (>2.0 kg/m²) (p=0.01). Multivariate analysis showed that creatinine clearance and (BW - preoperative BW)/BSA on POD 3 remained as independent predictive factors (p=0.04 and 0.04, respectively). CONCLUSIONS: We should aim for postoperative fluid management such that ((BW - preoperative BW)/BSA) ≤2.0 kg/m² on POD 3, especially in patients with low preoperative levels of creatinine clearance.