Dynamic behaviours of epoxy resin thin films during the curing process.

Epoxy resin thin films are widely used in applications such as coating materials, insulator films, and adhesives; accordingly, investigations of their physical properties have garnered increasing importance. Although the physical properties of thermoset epoxy thin films are strongly affected by the curing conditions, such as the heating temperature and curing time, the dynamic properties during the curing process have not been studied thoroughly. In this study, we investigated the thermal fluctuations on the surface of epoxy resin thin films using grazing-incidence X-ray photon correlation spectroscopy, to elucidate the dynamic behaviours during the curing process. We thus succeeded in observing the freezing of capillary waves during the thermal curing process. These results are expected to facilitate a deeper understanding of the curing mechanisms of various thin films.

Heterogeneous dynamics in the curing process of epoxy resins.

Epoxy resin is indispensable for modern industry because of its excellent mechanical properties, chemical resistance, and excellent moldability. To date, various methods have been used to investigate the physical properties of the cured product and the kinetics of the curing process, but its microscopic dynamics have been insufficiently studied. In this study, the microscopic dynamics in the curing process of a catalytic epoxy resin were investigated under different temperature conditions utilizing X-ray photon correlation spectroscopy. Our results revealed that the temperature conditions greatly affected the dynamical heterogeneity and cross-linking density of the cured materials. An overview of the microscopic mechanism of the curing process was clearly presented through comparison with the measurement results of other methods, such as 1H-pulse nuclear magnetic resonance spectroscopy. The quantification of such heterogeneous dynamics is particularly useful for optimizing the curing conditions of various materials to improve their physical properties.

[Two Cases of Hereditary Breast Cancer in Which Genetic Counseling Was Useful].

INTRODUCTION: The importance of genetic counseling has been noted for hereditary breast cancer. We report the cases of two 32-year-old woman, unmarried, BRCA mutation-positive patients. CASES: In Case 1, the chief complaint was awareness of a right breast mass. There was a family history of breast cancer(3 previous cases in the family). The BRCA2 mutation was positive during the BRACAnalysis test. Right breast mastectomy and axillary dissection were performed. Genetic counseling was performed postoperatively, and her eggs were cryopreserved. In Case 2, the chief complaint was calcification of the right breast. She also had a family history of breast cancer(3 previous cases in the family). The BRCA1 mutation was positive during the BRACAnalysis test. Nipple-sparing mastectomy and sentinel lymph node biopsy were performed, and the pathological diagnosis was DCIS. After genetic counseling, she did not desire the cryopreservation of her eggs. DISCUSSION: In these cases, the histological type, stage, subtype, BRCA mutation site, etc., were different from each other, and detailed support by genetic counseling was taken according to each medical condition such as surgery and postoperative adjuvant therapy.

Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer.

BACKGROUND: Taxanes are among the key drugs for breast cancer treatment. This study aimed to evaluate the efficacy of upfront weekly nanoparticle albumin-bound paclitaxel (Nab-PTX; 100 mg/m2) for human epidermal growth factor 2 (HER2)-negative breast cancer. PATIENTS AND METHODS: Patients with stage II to IV breast cancer received 12 cycles of weekly 100 mg/m2 Nab-PTX as first-line treatment. Preoperative chemotherapy with anthracyclines after Nab-PTX was recommended. RESULTS: From 2012 to 2014, we enrolled 66 patients. The overall response rate after Nab-PTX was 59.1% [95% confidence interval(CI)=47.2% to 71.0%), 63.6% in those with hormone receptor-positive tumors, and 36.4% in those with triple-negative tumors. The pathological complete response rate at surgery was 15% (95% CI=6.1% to 24.4%). Toxicity analysis showed grade 2 peripheral neuropathy in 38 patients (57.6%), grade 2/3 leukocytopenia in 29 (43.9%) and grade 2/3 liver dysfunction in five (7.5%). CONCLUSION: Weekly neoadjuvant Nab-PTX at 100 mg/m2 led to good response rates (59.1%) and was well tolerated.

Neutrophil/lymphocyte ratio has a prognostic value for patients with terminal cancer.

BACKGROUND: Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex. In this study, we evaluated the feasibility of neutrophil/lymphocyte ratio (NLR) as an index to estimate survival in terminal cancer patients. METHODS: NLR was calculated retrospectively based on blood tests performed at 3 months, 2 months, 4 weeks, 3 weeks, 2 weeks, 1 week, and within 3 days before death in 160 cancer patients (82 men, 78 women; age range, 33-99 years; mean age, 69.8 years). RESULTS: NLR increased significantly with time (P < 0.0001). Mean NLR was significantly higher in patients who died within 4 weeks (29.82) than in those who lived more than 4 weeks (6.15). The NLR cutoff point was set at 9.21 according to receiver operating characteristic curve analysis (area under the curve, 0.82; 95% confidence interval, 0.79-0.85). We inferred that life expectancy would be <4 weeks when NLR >9.21. The sensitivity, specificity, positive predictive value, and negative predictive value were 65.6, 84.1, 90.6, and 51.1%, respectively. The positive and negative likelihood ratios were 4.125 and 0.409, respectively. CONCLUSIONS: NLR appears to be a useful and simple parameter to predict the clinical outcomes of patients with terminal cancer.

Risk factors for conversion of laparoscopic cholecystectomy to open surgery associated with the severity characteristics according to the Tokyo guidelines.

PURPOSE: The aim of this retrospective study was to identify the risk factors associated with the severity characteristics in the Tokyo guidelines for conversion to open surgery in patients with acute cholecystitis (AC) who underwent laparoscopic cholecystectomy. METHODS: A total of 225 patients were enrolled in the study. The patients were classified into two groups: a conversion group and a no-conversion group. The preoperative characteristics and therapeutic strategy were analyzed as risk factors for conversion to open surgery. The postoperative outcomes were also analyzed. RESULTS: Conversion to open surgery occurred in 29 patients (12.9%), including seven patients (6.7%) with mild AC and 22 patients (18.5%) with moderate AC. A univariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h, an elevated C-reactive protein (CRP) value and the Tokyo guidelines 2013 (TG 13) severity classification. The multivariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h and a CRP value >11.5 mg/dl. CONCLUSIONS: A duration of symptoms longer than 72 h, which is included in the criterion for moderate AC severity in the TG 13, was an independent risk factor for conversion to open surgery. In addition, adoption of a high CRP value as an additional criterion for moderate AC may increase the utility of the TG 13.

Successful treatment of a common hepatic artery pseudoaneurysm using a coronary covered stent following pancreatoduodenectomy: report of a case.

This report presents the case of a common hepatic artery (CHA) pseudoaneurysm secondary to postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), which was successfully treated using a coronary covered stent. A 70-year-old female underwent subtotal stomach-preserving PD for middle cholangiocarcinoma. POPF was identified on postoperative day (POD) 7, and the patient suddenly lost 500 ml of blood via the abdominal drain on POD 19. Urgent celiac arteriography revealed a CHA pseudoaneurysm. A coronary covered stent was placed to prevent rupture of the pseudoaneurysm and to maintain hepatic arterial flow, instead of performing transarterial embolization. No vascular adverse events were encountered during or after the procedure. Computed tomography and angiography showed a patent stent graft and good hepatic arterial flow 9 months after placement of the stent. Endovascular stent-graft placement not only treated the pseudoaneurysm, but also preserved the arterial blood flow. This report describes the placement of a covered stent graft for delayed hemorrhage after PD.

Phase II clinical trial of high-dose toremifene as primary hormone therapy in aromatase inhibitor-resistant breast cancer.

BACKGROUND: Third-generation aromatase inhibitors(AIs)are now common in adjuvant hormone therapy for breast cancer in postmenopausal women. However, a suitable treatment has yet to be established for patients who develop cancer recurrence during or after adjuvant AI therapy. PATIENTS AND METHODS: This prospective study evaluated the efficacy and safety of 120mg/day toremifene citrate(TOR-120)administered orally to 23 patients with recurrent breast cancer who were receiving or had received adjuvant AI therapy. Primary therapy for recurrence was TOR-120 monotherapy. RESULTS: The response rate was 13. 0%(partial response: three patients), the clinical benefit rate was 78. 3%(partial response: three patients; long-term stable disease: 15 patients), and median time to progression was 8. 1 months. Grade 1 adverse events such as loss of appetite, sweating, flushing and edema face were observed. CONCLUSION: TOR-120 monotherapy was effective and safe as a primary hormone therapy for recurrent breast cancer unresponsive to AIs.

Effect of aromatase inhibitors on bone mineral density in a Japanese breast cancer population.

We retrospectively analyzed the bone mineral density (BMD) of postmenopausal Japanese women taking an aromatase inhibitor (AI), exemestane, anastrozole or letrozole, and calculated the decrease rate constant of BMD in each individual to compare the influence of the three AIs on BMD. We also aimed to evaluate the preventive effect of bisphosphonates (BPs) on the AI-induced decrease in BMD. The decrease rate constant of BMD (k(e)) in each individual was determined as a slope of linear regression of the relationship between time and logarithm of BMD value in each patient during the AI therapy. To compensate for the age-related change in BMD level, we estimated the age-related decrease rate constant of BMD (ke,0) in healthy Japanese postmenopausal women from the literature. AIs decreased BMD with a ke value of -0.0329 yr(-1), which was 4.7-fold larger than the k(e,0) value of -0.00699 yr(-1). No significant difference was detected in the influence on BMD among AIs. Co-administration of BP ameliorated the ke value to -0.0117 yr(-1), a value similar to k(e,0). The influence of AIs on BMD was quantitatively evaluated by using the decrease rate constant of BMD (k(e)). The present study also suggests that BPs may be useful to prevent the decrease in BMD induced by AIs.

Changes in the therapeutic strategy for acute cholecystitis after the Tokyo guidelines were published.

BACKGROUND: This study examined the feasibility of early laparoscopic cholecystectomy (ELC) for acute cholecystitis (AC) according to the Tokyo guidelines severity grade, and analyzed the changes in the therapeutic strategy for AC after the Tokyo guidelines were published. METHODS: A total of 225 patients were enrolled in this study. The therapeutic period was divided into two periods: before and after the publication of the Tokyo guidelines (prior to and including 2007, and from 2008, respectively). RESULTS: Comparing the surgical strategy between ELC and delayed laparoscopic cholecystectomy (DLC), significant differences were found in the length of preoperative hospital stay and total hospital stay for cases of mild AC compared with moderate AC. With conversion to open surgery, postoperative complications including postoperative bile leak were not significantly different. Since ELC was performed significantly more often after publication of the guidelines, preoperative, postoperative, and total hospital stays were significantly shorter in the later period. CONCLUSION: ELC is a safe and effective therapeutic strategy for both mild and moderate AC. The Tokyo guidelines resulted in a significant increase in the performance of ELC and significantly reduced preoperative and total hospital stays without increasing intra- and postoperative complications.

Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer.

PURPOSE: Metronomic combination chemotherapy with the oral fluoropyrimidine doxifluridine/5'-deoxy-5-fluorouridine (5 -DFUR) and oral cyclophosphamide (C) showed promising efficacy in a single-arm study. The oral fluoropyrimidine capecitabine was designed to deliver 5-fluorouracil preferentially to tumors, potentially improving efficacy over doxifluridine. We conducted a phase II multicenter study to evaluate an all-oral XC combination in patients with HER2-negative metastatic breast cancer (MBC). MATERIALS AND METHODS: Patients received capecitabine 828 mg/m(2) twice daily with cyclophosphamide 33 mg/m(2) twice daily, days 1-14 every 3 weeks. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between May 2007 and April 2009, 51 patients were enrolled and 45 were included in the efficacy analysis. The median follow-up was 18.1 months. ORR was 44.4% and stable disease (≥24 weeks) was achieved in 13.4%, resulting in a 57.8% clinical benefit response rate. Median PFS was 12.3 months (95% confidence interval: 8.9-18.9 months). Median PFS was 10.7 months in triple-negative disease and 13.2 months in estrogen-receptor positive, HER2-negative disease. The 1- and 2-year OS rates were 86 and 71%, respectively. Median OS has not been reached. Grade 3 adverse events comprised leukopenia (26%), neutropenia (16%), and decreased hemoglobin (2%). There was no grade 3 hand-foot syndrome. CONCLUSIONS: Oral XC is an effective first- or second-line therapy for MBC, demonstrating high activity in both luminal A and triple-negative disease with few severe side effects. This metronomic oral combination chemotherapy could be beneficial for the treatment of HER2-negative MBC.

Bacteriological analysis of bile in acute cholecystitis according to the Tokyo guidelines.

BACKGROUND: We performed bacteriological analysis of bile in acute cholecystitis (AC) patients graded in severity according to the Tokyo guidelines. METHODS: We enrolled 163 AC patients in whom bacteriological analysis of bile was performed. RESULTS: Significant differences in age (60 vs. 67 years), body temperature (BT) (37.2 vs. 37.6°C), white blood cell count (13,033 vs. 15,177/mm(3)), and serum C-reactive protein (CRP) (8.9 vs. 16.9 mg/dL) were found between the Mild and Moderate severity groups. The prevalence of bactibilia differed significantly between Mild and Moderate patients (45.3 vs. 67.0%, P = 0.0107); however, there were no significant differences in the bacterial strains, prevalence of antimicrobial resistance, or polymicrobial isolation frequency between the 2 groups. Our local antibiogram revealed that several microorganisms showed higher resistance rates; these were also isolated even in Mild cases. Advanced age, high BT, high serum CRP, and presence of marked local infection were identified as being significantly associated with high risk of bactibilia. Receiver operating characteristic curve analysis indicated the optimal cutoff value of age to be 65 years, of BT to be 37.5°C, and of serum CRP to be 13.4 mg/dL. CONCLUSION: Adequate broad-spectrum antimicrobial therapy should be administered perioperatively even for Mild patients classified according to the current Tokyo guidelines. These results suggest that more precise severity grades may need to be established, including age and CRP as additional parameters.

Combined hepatic resection with the inferior vena cava and diaphragm and reconstruction using an equine pericardial patch: report of a case.

We herein report a case of combined hepatic resection with inferior vena cava (IVC) and diaphragm resection, and reconstruction using an equine pericardial patch. A 54-year-old woman showed hepatic cancer recurrence on radiological imaging, with invasion to the caudate lobe of the liver, IVC, diaphragm, and adrenal gland. We resected 10 × 5 cm of the diaphragm. After dissecting the hepatic parenchyma, the caudate lobe was connected only to the IVC. Clamping of the IVC was performed between the IVC below the confluence of the hepatic vein and the suprarenal IVC. A 6 × 3-cm segment of the IVC was then resected. The IVC and diaphragm were reconstructed using an equine pericardial patch, as both defects were too large to repair without a patch. The equine pericardium represents a suitable graft material for repairing both the IVC and diaphragm. Further investigation is needed to determine the durability and anti-infection properties of equine pericardial grafts.

Pancreatic adenosquamous carcinoma presenting as splenic rupture: report of a case.

A 58-year-old female patient presented with the sudden onset of left upper quadrant pain. The physical examination revealed the presence of shock status. Abdominal computed tomography revealed splenomegaly with a huge mass inside the spleen, and massive fluid collection in the abdominal cavity. After splenic artery embolization, laparotomy was performed. The operative findings revealed intra-abdominal hemorrhage and rupture of the lower pole of the spleen. Furthermore, a palpable solid mass was observed at the splenic hilum, and distal pancreatectomy with splenectomy was performed. The macroscopic findings revealed a pancreatic tail tumor at the splenic hilum directly invading the splenic parenchyma. Microscopic examinations showed the tumor to consist of squamous cell carcinoma. Furthermore, old and new thrombi were observed inside small splenic arteries. These findings were considered to represent invasion of pancreatic adenosquamous carcinoma to the spleen, and rupture of the spleen was attributed to splenic ischemia resulting from cancer invasion and splenic vein obstruction.

Twenty years of countermeasures against postoperative methicillin-resistant Staphylococcus aureus infections.

PURPOSE: A total of 7345 cases of digestive organ surgery were investigated over the course of 20 years. METHODS: Owing to the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections, we classified our countermeasures into periods A (September 1987 to February 1990), B (March 1990 to February 1997), C (March 1997 to February 1999), D (March 1999 to October 2004), and E (November 2004 to August 2007), and compared the number of infections during these periods. In period B, cefazolin and cefotiam were administered as prophylaxis. The treatment continued for 4 days, including the day of surgery. The patients undergoing endotracheal intubation or tracheotomy were managed with nonscreening pre-emptive isolation and cohorting (NSPEI&C), regardless of whether MRSA was present. However, NSPEI&C was halted in period C, but it was thereafter implemented again, and prophylactic antibiotics were administered only on the day of surgery during period D. In period E, prophylactic antibiotics were administered for 3 days. RESULTS: In period A, MRSA was contracted in 4.1% (34/833) of patients. In period B, the MRSA isolation rate decreased to 0.3% (8/2722). In period C, the MRSA isolation rate increased to 3.4% (23/681). In period D, the MRSA isolation rate fell to 2.2% (40/1807). In period E, MRSA isolation cases significantly decreased to 0.4% (5/1302; P < 0.002 vs period D). CONCLUSION: The comprehensive management, selection of prophylactic antibiotics, and NSPEI&C were all considered to be effective.

Antibiotic time-lag combination therapy with fosfomycin for postoperative intra-abdominal abscesses.

The first-line treatment for intra-abdominal abscess is source control. Sometimes, however, source control is too invasive for relatively small abscesses and is not feasible due to the risk of injury to some organs. Based on reports that fosfomycin (FOM) can break up biofilms to enhance the permeability of other antibiotics, we investigated the FOM time-lag combination therapy (FOM-TLCT). We enrolled 114 patients who had intra-abdominal abscess after gastrointestinal surgery and examined the efficacy of FOM-TLCT using the same therapeutic antibiotic (TA) as that which had been used previously, but had proven ineffective, at the same dose schedule. The efficacy endpoint determination was carried out as follows: among the systemic inflammatory response syndrome (SIRS)-positive cases, even after administration of TA, excellent outcome was defined as SIRS negative within 7 days of FOM-TLCT with TA without the need for other treatment, including other antibiotics or drainage. Of the 114 patients enrolled, 104 cases (SIRS positive 73; SIRS negative 31) were assessed. Ten patients were excluded; four had received TA at higher doses, three had received different TAs, and three were considered to have bacteria resistant to TAs. Among these patients, 86.3% (63/73) of the SIRS-positive cases were classified as excellent, and 90.3% (28/31) of the SIRS-negative cases were classified as effective. In total, the efficacy rate was 87.5% (91/104). The total no-response rates were 12.5% (13/104). FOM-TLCT seems to be effective for treating refractory intra-abdominal abscess.

[Three cases of biliary tract cancer with positive surgical margin obtained a long-term survival after multimodality therapy].

We report three cases of biliary tract cancer with positive surgical margin obtained a long-term survival after multimodality therapy. Case 1: A 58-year-old man had operated PPPD for middle part of biliary tract cancer. Final pathological findings revealed HM2. Hepatic metastasis and anastomotic recurrence were observed, postoperatively. RFA and chemoradiation therapy were performed against these lesions. Nevertheless, the patient died of sepsis associated with hepatic abscess caused by cholangitis 5 years and 10 months after surgery. Case 2: A 72-year-old man had operated for upper part of biliary tract cancer. Intra-operative pathological findings revealed HM 2 and DM 2, extra-bile duct resection was performed for this lesion. After surgery, radiation therapy, systemic chemotherapy and hepatic arterial chemotherapy were performed, nevertheless the patient died of cancer 2 years and 6 months after surgery. Case 3: A 75-year-old man had operated for upper part of biliary tract cancer. Intra-operative pathological findings revealed HM 2 and DM 2, an extra-bile duct resection was performed for this lesion. After surgery, chemoradiation therapy, hepatic arterial chemotherapy and systemic chemotherapy were performed, nevertheless the patient died of cancer 3 years and 6 months after surgery.

Efficacy of doxifluridine combined with weekly paclitaxel therapy in the treatment of advanced or recurrent breast cancer: results of the JMTO BC01 phase II trial.

We conducted a phase II study to determine the availability and safety of combination chemotherapy with weekly paclitaxel and doxifluridine (a capecitabine metabolite) in the treatment of advanced or recurrent breast cancer. Patients were treated with a combination chemotherapy regimen: doxifluridine was orally administered at 800 mg/day for 14 days, followed by a 7-day washout period. Paclitaxel was given intravenously on days 1 and 8 at 80 mg/m2 for 1 h, followed by a 1-week washout period. This 3-week cycle of therapy was repeated as long as possible (at least eight cycles) until the progression of the tumor and drug-related adverse effects were no longer observed. From May 2003 to December 2005, 26 patients were enrolled in the study. The overall response rate was 53.8% (95% confidence interval, 33.4-73.4%). The clinical benefit rate, including long-term no change, was 65.4% (95% confidence interval, 44.3-82.8%). Time to progression and survival time were 297 and 1182 days, respectively, for the 26 enrolled patients. No severe toxicities were observed. Grade 3/4 leucopenia in three patients, neutropenia in five patients, increased serum creatinine in three patients, hypercalemia in one patient, hypocalcemia in one patient, nausea/vomiting in two patients, and diarrhea in one patient. The good response rate and long time to progression and overall survival time of this doxifluridine combined with weekly paclitaxel therapy indicate its potential as a first-line or second-line treatment for advanced or recurrent breast cancer patients.

Paget's disease of the breast in a woman with neurofibromatosis.

Paget's disease of the breast is a rare and specific type of breast carcinoma in the nipple or areola. On the other hand, neurofibromatosis (NF) is also a rare neurocutaneous disease, which is inherited and affects mainly the skin and the nervous system. In addition, NF is rarely associated with malignant tumors. We present a case of Paget's disease concomitant with NF type 1 in a 66-year-old woman.

[A case of resectable solitary liver metastasis from breast cancer].

We report a case of resectable solitary liver metastasis from breast cancer. A 53-year-old woman underwent a pectoral muscle-preserving mastectomy for T1 N0M0 (Stage I) left breast cancer in May 2000. Histopathologic diagnosis was medullary carcinoma. Thereafter, the patient was followed up with adjuvant chemotherapy. A solitary tumor in the right lobe of the liver at S6 was found 10 months after mastectomy by ultrasonography. With a diagnosis of liver metastasis from breast cancer, right hepatectomy was performed in May 2001. At present, she remains disease free for 4 years after hepatectomy. We think that a surgical procedure for liver metastasis from breast cancer, if possible, is beneficial in prolonged survival.