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Background/aim The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). Patients and methods We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. Results High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. Conclusion Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.

Background/aim Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). Patients and methods GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. Results Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. Conclusion GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

Background: The skin's condition is altered in lymphedema patients, and evaluating this change is important. Some noninvasive methods for evaluating skin condition have been reported, especially in upper limb lymphedema. However, evaluating the skin in lower limb lymphedema remains challenging and is often limited to palpation. We aimed to develop a noninvasive skin evaluation method for lower limb lymphedema patients. Methods and Results: Twenty-five lower limb lymphedema patients were included. Skin induration and elasticity were measured using Indentometer® IDM 400 and Cutometer® MPA580. The relationship between the properties of skin from the healthy forearm and thigh, those of the affected thigh, and age was analyzed. Predicted skin induration age (IA) and elasticity age (EA) were calculated from the forearm, whereas actual values were calculated from the thigh, and the differences (ΔIA and ΔEA) were assessed. Patients were classified according to the International Society of Lymphology clinical staging system, and the differences in ΔIA and ΔEA were analyzed among the three groups (healthy, stage I/IIa, and stage IIb/III). Skin biopsy was performed in five unilateral lower limb lymphedema patients, and the dermal elastic fiber area was determined using microscopy with Elastica van Gieson staining. ΔEA significantly increased with disease progression, but ΔIA did not change significantly. Microscopy revealed elastic fiber filamentous changes, with decreased elastic fiber areas in lymphedema-affected skin. Conclusion: To our knowledge, this is the first report to evaluate lower limb skin elasticity in lymphedema quantitatively and noninvasively. ΔEA is useful for evaluating skin condition progression in lymphedema patients.

There has been limited data on the influence of sex on development of thrombosis in patients with coronavirus disease 2019 (COVID-19).The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into the men (N = 1885) and women (N = 1009) groups.There were no significant differences in D-dimer levels at admission between men and women. Men had more severe status of the COVID-19 at admission compared with women (Mild: 57% versus 66%, Moderate: 34% versus 29%, and Severe: 9.1% versus 5.7%, P 0.001). Men more often received pharmacological thromboprophylaxis than women (47% versus 35%, P 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4-1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19 during the hospitalization (Mild: 0.3% versus 0.0%, Moderate: 1.6% versus 1.0%, and Severe: 11.1% versus 4.3%). Even after adjusting confounders in the multivariable logistic regression model, the excess risk of men relative to women remained significant for thrombosis (adjusted OR, 2.51; 95%CI, 1.16-5.43, P = 0.02).In the current large observational study of patients with COVID-19, men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women, which could be helpful in determining the patient-specific optimal management strategies for COVID-19.

Purpose The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC).PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated.No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049).PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

Background: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on the pancreatic cancer survival and recurrence after curative surgery followed by adjuvant chemotherapy. Patients and Methods: This study included 155 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. Results: An ACCI of 8 was regarded as the optimum critical point of classification considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 25.7% and 19.0% in the ACCI-low group, respectively, and 7.6% and 0% in the ACCI-high group, which amounted to a statistically significant difference (P = 0.019). The RFS rates at 3 and 5 years after surgery were 17.3% and 13.8% in the ACCI-low group, respectively, and 7.1% and 0% in the ACCI-high group, which amounted to a marginally statistically significant difference (P = 0.104). A multivariate analysis showed that the ACCI was a significant independent risk factor for both the OS and RFS. Conclusions: The ACCI was a risk factor for the OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. An effective plan is needed for determining the optimum surgical strategy according to the ACCI.

Background/aim Lymphovascular invasion (LVI) is recognized as a prognostic predictor of recurrence in certain carcinomas. According to current Japanese guidelines, however, in gastric cancer, LVI is not clinically useful information, except for predicting the curability of endoscopic resection. We clarified the clinical significance of LVI in gastric cancer and its correlation with disease prognosis. Patients and methods A total of 2,090 cases of gastric cancer undergoing radical gastrectomy were enrolled. The correlation of LVI and other histopathological factors was evaluated with regards to patient prognosis. Results LVI(+) was noted in 894 cases. A multivariate analysis showed that pT, pN, and LVI were independent risk factors for patient prognosis. In pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVI(+) cases were lower than those in LVI(-) (60.9% vs. 76.7%, p=0.005). Conclusion LVI in gastric cancer is an independent prognostic factor, and tends to worsen prognosis, especially in advanced cancers with lymph node metastases.

Background Pancreatic cancer is a fatal disease with a poor prognosis. Pancreatic cancer is often unresectable at the time of diagnosis, so the analysis of risk factors in patients with indications for surgery is important. We investigated the impact of intraoperative blood loss (IBL) on survival and recurrence in patients with stage II/III pancreatic cancer after curative surgery. Patients and methods This study included 76 patients who underwent curative surgery for stage II/III pancreatic cancer between 2007 and 2012. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. Results IBL of 1,000 ml was considered to be the optimal cut-off value for classification based on a receiver operating characteristic (ROC) curve analysis. The OS rates at 5 years after surgery in the groups with low and high IBL were 36.6% and 11.4%, respectively, which was a statistically significant difference (p=0.003). The RFS rates at 1 year after surgery were 49.8% and 24.6%, respectively, which was a significant difference (p=0.045). A multivariate analysis demonstrated that IBL was a significant independent risk factor for OS. Conclusion IBL is an independent prognostic factor after curative resection of stage II/III pancreatic cancer. The reduction of bleeding during surgery is necessary to improve the results of pancreatic cancer surgery.

A 55-year-old man was admitted to our hospital for examination and treatment of a transverse colon tumor detected at a nearby hospital. After CT, FDG-PET, and laparotomy biopsy, he was diagnosed with neuroendocrine cancer(Ki-67 index 40%)without distant metastasis. He underwent transverse colectomy. The pathological diagnosis was transverse colon neuroendocrine cancer(Ki-67 index 24.7%). Six courses of carboplatin and etoposide therapy as adjuvant chemotherapy were administered. Seven months after surgery, he developed lung metastasis that was surgically removed by partial lung resection. Eighteen months after the initial surgery, liver metastasis developed in S5 and S8. A right hepatic lobectomy was performed and there has been no recurrence after hepatectomy. The patient remains alive at 3 years and 4 months after initial treatment.

In digital replantation, Kirschner wire (K-wire) fixation has commonly been used for osteosynthesis. On the other hand, K-wires are often obtrusive because of protrusion from the replanted digit. We describe a case series treated using hydroxyapatite/poly-L-lactide (HPLLA) threaded pins, which are not only bioabsorbable, but also osteoconductive, for osteosynthesis in crushed amputation or comminuted fracture, including distal phalanx amputation. Using an HPLLA threaded pin, 10 digital replantations were performed between July 2016 and April 2018. The precisely cut pin is manually pushed into the fracture site as an intramedullary nail. The pin is first pushed into the distal site, and then into the proximal site, after drilling with a K-wire of the same diameter as the pin. All amputations were crush type, and levels of amputations were Tamai zone I in three cases, zone II in two and zone III in five. Eight of the 10 digits survived. The two digits that did not survive showed venous insufficiency. Bone union of the eight digits was successfully obtained after 9-19 weeks (median 12 weeks). No adverse events occurred such as distortion of the pin, infection or foreign body reaction. The HPLLA threaded pin may be an adequate device to fix fractures in digital replantation.

Background This study aimed to investigate the impact of postoperative complications (PCs) in patients with pathological stage (pStage) II or III gastric cancer (GC) who received adjuvant chemotherapy with S-1 after curative surgery. Patients and methods Altogether, data for 226 patients were examined retrospectively. The relationship between PCs and clinicopathological features and survival were examined. Results Recurrence-free survival was significantly worse in the group with PCs than in the PC-negative group. On multivariate analysis, having PCs of grade 2 or more was an independent risk factor for recurrence (hazard ratio=1.721; 95% confidence intervaI=1.014-2.920; p=0.044). In addition, for each pStage analysis, having PCs of grade 2 or more was a risk factor for recurrence even in patients with pStage II GC. Conclusion PC of grade 2 or more was an independent risk factor for recurrence in patients with pStage II GC who received adjuvant chemotherapy with S-1 after curative gastrectomy. Thus, for patients with PCs, even for those with pStage II GC, more effective adjuvant chemotherapy, such as S-1 plus docetaxel, may be needed.

Background: The C-reactive protein (CRP)-to-serum albumin ratio is associated with a poor prognosis in patients with several cancers. The purpose of this study was to clarify the relationship between the preoperative CRP/Alb ratio and overall survival of pancreatic ductal adenocarcinoma (PDAC) in patients who received radical surgery and S-1 adjuvant chemotherapy. Patients and Methods: We included 117 patients who underwent radical surgery with S-1 adjuvant chemotherapy. We constructed receiver operating characteristic curve (ROC curve) of the CRP/Alb ratio to determine the cut-off value. We analyzed the relationship among the CRP/Alb ratio, clinicopathological status, and survival. Results: The optimal cut-off value of the CRP/Alb ratio was 0.036. All patients were divided into a high-ratio group (CRP/Alb ratio ≥0.036) and low-ratio group (CRP/Alb ratio

Background: Innominate artery aneurysm (IAA) is a rare cervical artery aneurysm. Although atherosclerosis is its most common cause, IAAs due to cervical injury are often reported. Operative indications for IAAs include rupture or symptomatic aneurysm, saccular aneurysm, aneurysm with a diameter of 3 cm or greater, and aneurysmal change of the origin of the innominate artery. Although the ligature of the innominate artery or open surgical repair is well described, the usefulness of endovascular repair has also recently been reported. Herein, we report a case of traumatic IAA with infection in the cervical region after tracheostomy. Case Presentation: A 40-year-old man with cholecystolithiasis planned to undergo laparoscopic cholecystectomy at another hospital. Urgent tracheostomy was performed because of laryngeal edema at the induction of general anesthesia. Enhanced computed tomography angiography 1 week after the tracheostomy revealed a saccular IAA. The patient was deemed to be at high risk for aneurysm rupture and was referred to our hospital. Preoperative Matas test, Allcock test, and innominate arterial stump pressure measurement were performed to assess the cerebral blood flow and ischemic tolerance of the brain. These examinations showed the patency of the circle of Willis. An axillo-axillary artery bypass with coil embolization of the innominate artery was performed to avoid postoperative vascular graft infection. No postoperative complications such as infection or cerebral infarction occurred. Magnetic resonance imaging angiography performed 6 months after surgical treatment showed that the aneurysm had disappeared, and patency of the bypass graft was present. There were no postoperative complications, such as neurological deficits or graft infection, at more than 5 years after surgery. Conclusions: We report a successfully treated case of IAA after tracheostomy. Axillo-axillary artery bypass with coil embolization of the innominate artery is an effective treatment of IAA with cervical infection.

Summary Background Routine therapy of metabolic bone disorder (MBD) after gastrectomy for gastric cancer has not been established yet. We have reported that administering an active vitamin D3 agent to patients who had undergone gastrectomy for gastric cancer improved MBD. Recently, the usefulness of alendronate, an osteoclast inhibitor, has been reported for MBD. Here we report the effects of alendronate for MBD after gastrectomy for gastric cancer. Methods Dual energy X-ray absorptiometry was performed consequently in 14 patients, who had been gastrectomized for gastric cancer and survived more than 5 years without recurrence, to evaluate the MBD and compared before and after treatment. The 14 patients were divided into two groups: in group VD3, 1 μg/d of alfacalcidol, an active vitamin D3 agent, was administered; and in group ALN, 5 mg/d or 35 mg/wk of alendronate or both alfacalcidol and alendronate were administered. These drugs had been administered to the patients for > 2 years, and the patients were followed up. Results After 12 months, dual energy X-ray absorptiometry revealed that bone mineral density and T score were significantly increased in group ALN. Changes in serum bone-specific alkaline phosphatase after 24 months were −9.1 μg/L in the ALN group and 3.75 μg/L in the VD3 group, showing a significant difference (p = 0.02). No serious adverse events were observed in either group. Conclusion These results showed the usefulness of alendronate and alendronate+activated vitamin D3 combination therapy, suggesting that these treatments might prevent postgastrectomic MBD.

Some odorants have physiological and psychological effects on organisms. However, little is known about the effects of inhaling them, particularly on the central nervous system. Using DNA microarray analysis, we obtained gene expression profiles of the hypothalamus from restraint stressed rats exposed to racemic (R,S)-linalool. Hierarchical clustering across all probe sets showed that this inhalation of (R,S)-linalool influenced the expression levels of a wide range of genes in the hypothalamus. A comparison of transcription levels revealed that the inhalation of (R,S)-linalool restored the expression of 560 stress-induced probe sets to a normal status. Gene Ontology (GO) analysis showed that these genes were associated with synaptic transmission via neurotransmitters including anxiolytic neuropeptides such as oxytocin and neuropeptide Y. These genes also included several major histocompatibility complex (MHC) class I molecules necessary for neural development and plasticity. Moreover, Upstream Regulator Analysis predicted that the hormone prolactin would be activated by the inhalation of (R,S)-linalool under stress. Our results reveal some of the molecular mechanisms associated with odor inhalation in the hypothalamus in organisms under stress.

Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established. In this study, we analyzed human and mouse atherosclerotic tissues to gain insight into the arachidonyl-PC metabolism involving LPCAT3 using imaging mass spectrometry. The data revealed a complementary distribution of arachidonyl-PC and LPC in human atherosclerotic tissues with arachidonyl-PC decreasing and LPC increasing as atherosclerosis progressed. Furthermore, we found a homologous distribution of LPCAT3 expression and arachidonyl-PC based on atherosclerotic progression. In contrast, in ApoE-deficient mice, atherosclerosis increased both arachidonyl-PC accumulation and LPCAT3 expression. Taken together, these findings suggest that the regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans.

Background/aim The KIAA1199 gene has been associated with cancer-cell proliferation, but its functions remain poorly studied. Here, we examined the clinical significance of the KIAA1199 mRNA levels in locally advanced gastric cancer (GC). Materials and Methods/Results: Using samples from 254 patients with stage II/III GC, we found significantly higher KIAA1199 levels in cancerous tissues compared to adjacent normal mucosa (ANM). There was no significant relationship between KIAA1199 expression and clinical features. Although overall survival rates (OSR) of patients, who underwent surgery did not correlate with KIAA1199 expression, patients who underwent adjuvant chemotherapy with S-1 and had high KIAA1199 levels displayed significantly lower OSR. KIAA1199 knock down (KIAA1199-KD) suppressed proliferation, invasiveness, and sensitivity of GC cells to 5-fluorouracil (5-FU). Conclusion KIAA1199 expression appears to be a promising prognostic marker in patients with locally advanced GC, who underwent postoperative adjuvant chemotherapy with S-1. KIAA1199 may represent a novel target for GC pharmacotherapy.

Background/Aim: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. Patients and Methods: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. Results: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). Conclusion: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

The pancreatic cancer microenvironment is crucial in cancer development, progression and drug resistance. Cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze the whole cancer-stromal interactome. Here we studied 14 resected pancreatic cancer specimens (8 pancreatic adenocarcinoma (PDAC) patients as a cancer group and 6 intraductal papillary-mucinous adenoma (IPMA) patients as a control). Shotgun proteomics of the stromal lesion dissected with laser captured microdissection (LCM) was performed, and identified 102 differentially expressed proteins in pancreatic cancer stroma. Next, we obtained gene expression data in human pancreatic cancer and normal pancreatic tissue from The Cancer Genome Atlas database (n = 169) and The Genotype-Tissue Expression database (n = 197), and identified 1435 genes, which were differentially expressed in pancreatic cancer cells. To identify relevant and druggable cancer-stromal-interaction targets, we applied these datasets to our in-house ligand-receptor database. Finally, we identified 9 key genes and 8 key cancer-stromal-interaction targets for PDAC patients. Furthermore, we examined FN1 and ITGA3 protein expression in pancreatic cancer tissues using tissue microarrays (TMAs) of 271 PDAC cases, and demonstrated that FN1-ITGA3 had unfavorable prognostic impact for PDAC patients.

Introduction We propose a novel technique to close Petersen's defect using barbed sutures and evaluate the safety and usefulness of this technique by assessing postoperative complications and measuring the time required to close Petersen's defect. Materials and surgical technique Petersen's defect was closed laparoscopically with running non-absorbable barbed sutures (V-loc®) after a nodal dissection and reconstruction procedure. First, the transverse colon was elevated cranially, making the dorsal side of the transverse mesocolon a flattened surface. The intersection of the transverse mesocolon and Roux limb mesentery was then identified, and closure was started from this point. We continued to sew the transverse mesocolon and Roux limb mesentery toward the transverse colon with a running suture. At the end of suturing, we placed one or two stitches in the fatty appendices of the transverse colon and cut the free tail of thread as short as possible. Discussion We investigated postoperative complications and measured the time required to close Petersen's defect in 64 patients who underwent this technique. The results showed that this closure technique could be performed promptly and safely regardless of the patient, surgical procedure, and the experience of the operator.

Background The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation. Methods This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications. Results No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7. Conclusion Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation. Clinical question/level of evidence Therapeutic, II.

A 63-year-old man was admitted to our hospital for examination and treatment of a pancreatic head tumor detected at a nearby hospital. After CT, EUS-FNA, and PET-CT, he was diagnosed with unresectable pancreatic cancer with liver metastasis. After 9 courses of gemcitabine and nab-paclitaxel therapy, the primary tumor was dramatically reduced in size and the liver metastasis had disappeared. He underwent subtotal stomach-preserving pancreaticoduodenectomy. The postoperative diagnosis according to the General Rules of the Study of Pancreatic Cancer(7th edition)was Ph, TS1(15mm), adenosquamous carcinoma, ypT3, ypRP1, ypPL1, R0, ypN0(0/29), M0, CY0, ypStage ⅡA. The histological response was Grade 2. The patient remains alive without recurrence 5 months after surgical resection.

An 84-year-old man with a thoracoabdominal aortic aneurysm was treated using a fenestrated stent graft with a preloaded guidewire system under local anesthesia. He suffered from severe chronic obstructive pulmonary disease. We successfully placed 4 bridging stent grafts for perfusion of the celiac artery, superior mesenteric artery, and bilateral renal arteries via the 4 fenestrations. A preloaded wire system was used to insert a catheter into the celiac artery from the left brachial artery. Our findings indicate that a fenestrated stent graft with a preloaded wire system may expand the indication for treating thoracoabdominal aortic aneurysms in high-risk patients.

Vasa vasorum (VV) and lymphatic vasa vasorum (LVV) form their own networks in the adventitia. VV supply the aorta with nutrition and oxygen; however, the distribution and role of LVV remains to be determined. The purpose of this study was to investigate differences in the distribution of VV and LVV along the aorta.Aortic samples were obtained from 22 autopsy cases without medical history of aortic diseases. Aortic segments were classified as arch (Ar), descending thoracic (De), suprarenal abdominal (S-Ab), and infrarenal abdominal (I-Ab). Adventitial VV and LVV were identified immunohistochemically.VV were most dense in the arch aorta, becoming less dense along the aorta in more distal segments, with the lowest density occurring in the infrarenal abdominal aorta. There was a significant correlation between the numbers of VV and medial thickness in the total aortic segments (r = 0.518, p0.01). In contrast, there was no significant correlation between the number of LVV and medial thickness in any aortic segments. However, there was a significant correlation between the number of LVV and intimal thickness in I-Ab (r = 0.425, p0.05).The distributions of adventitial VV and LVV were characteristic along the aortic segments. Differences in the distributions may imply the prevalence of aortic diseases such as dissection, abdominal aortic aneurysm, and atherosclerotic occlusive disease in each aortic segment.

The standard therapy for Stage IV gastric cancer is chemotherapy. It is not certain, but conversion surgery is expected to be effective. We report the cases of 3 patients who achieved long-term survival after conversion surgery. Case 1 was of a 59- year-old woman. The tumor was classified as L-Less Post, Type 2, tub1, cT3N2M1(#16a2lat), Stage IV. Then, we initiated S-1 plus cisplatin and the LN achieved PRafter 4 courses. We performed distal gastrectomy with D2 lymph node dissection in February 2011. It was classified as ypT2N2 and the primary lesion was histologically classified as Grade 1a. Case 2 was of a 74- year-old man. The tumor was classified as UM-Less Ant, Type 3, por1, cT3N2H0P1CY1, Stage IV. Then, we initiated docetaxel plus cisplatin plus S-1 and the primary tumor achieved PRafter 6 courses. There were no new tumors and we conducted a laparoscopic examination. After the decision of P0CY0, we performed total gastrectomy with D2 lymph node dissection in April 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 2. Case 3 was of a 64-yearold woman. The tumor was classified as UM-Less, Type 3, por1, cT3N2H1M0(liver), Stage IV. Then, we initiated capecitabin plus cisplatin and liver metastasis achieved PRafter 6 courses. We performed total gastrectomy with D2 lymph node dissection in July 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 1b. All postoperative chemotherapy courses were of only S-1. In case 1, the para aortic LN exhibited recurrence 6 months postoperatively. We initiated weekly paclitaxel as second-line therapy. It achieved CRafter 6 courses, and the same trend was maintained. In cases 2 and 3, no therapy was administered after 8 S-1 courses, but no recurrences occurred. All patients survived after 62-77 months postoperatively. A new clinical trial is needed to prove the improvement in prognosis for Stage IV gastric cancer after conversion surgery.

The safety and feasibility of administering S-1 adjuvant chemotherapy for pancreatic cancer has not yet been fully evaluated in elderly patients.This retrospective study selected patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II disease or lower or stage III disease with combined resection of the celiac artery, and received adjuvant S-1 at our institution. The patients were categorized into two groups: non-elderly patients (70 years of age: group A) and elderly patients (70 years of age: group B). The toxicity and S-1 continuation rates were compared between the two groups.A total of 76 patients were evaluated in the present study. There were no grade 4 toxicities. The incidences of grade 3 hematological and non-hematological toxicities were5 % in both groups, and the differences were not significantly different. The continuation rate at 6 months was 60.5 % in group A and 72.7 % in group B, which was also not significantly different.These results suggest that S-1 adjuvant chemotherapy for pancreatic cancer is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for clinical trials.

STUDY DESIGN This is a case-control study. OBJECTIVE The present study aimed to compare the cross-sectional areas of the psoas major and multifidus muscles between elderly patients with adult spinal deformity (ASD) and age-matched and body weight-matched controls, and to evaluate the associations between the cross-sectional areas of these muscles and the severity of spinal deformity. SUMMARY OF BACKGROUND DATA The study included 49 female kyphosis patients with mild scoliosis (Cobb angle

A 63-year-old man underwent low anterior resection for rectal cancer.A synchronous liver metastasis located in segment 8 was 12 cm in diameter and unresectable due to its proximity to the inferior vena cava(IVC).The postoperative pathological findings revealed a T3(SS), N0, M1(liver)Stage IV tumor, and wild type K-RAS was expressed.We chose FOLFIRI plus cetuximab(Cmab)for first-line chemotherapy.After 6 courses, we changed the molecular target drug from Cmab to bevacizumab( Bmab)because the liver metastasis remained unresectable.The patient had long-term stable disease(SD)for approximately 30 months with the FOLFIRI-based regimen.We then changed the regimen to mFOLFOX6 plus Bmab for second-line, Cmab for third-line, and trifluridine/tipiracil hydrochloride for fourth-line chemotherapy to treat progressive disease(PD).After treatment with these chemotherapies, the patient wished to continue treatment.We restarted FOLFIRI plus Bmab for fifth-line chemotherapy as his general condition was still good.Consequently, his tumor markers levels decreased with stabilization of the disease on CT scans, and he continued therapy for 6 months while maintaining a good quality of life.This case suggested that rechallenge with anti-cancer agents could be effective and improve the prognosis of colorectal cancer patients after using all key drugs.

This study aimed to evaluate the safety and feasibility of pancreatic surgery for pancreatic cancer in elderly patients.In total, 9 patients underwent pancreatic surgery for pancreatic cancer between April 2005 and March 2014. The surgical complications were evaluated by Clavien-Dindo classification.The median operating time was 420(range: 354-503)min and the median blood loss was 640(range: 350-1,170)mL. Grade 2 or higher complications were observed in 3 patients. Pancreatic fistula(Grade 3b)was observed in 1 patient, delirium was observed(Grade 2)in 1 patient, and portal vein thrombosis(Grade 2)was observed in 1 patient. No surgical mortality was observed.Our results suggest that pancreatic surgery is a safe and feasible treatment for pancreatic cancer in elderly patients.

The aim of this study was to evaluate the safety of laparoscopic-assisted colorectomy(LAC)for elderly patients more than 70 years old.The outcomes of 131 patients more than 70 years old who underwent LAC between April 2013 and March 2014 were retrospectively analyzed.Morbidity and mortality were evaluated using the Clavien-Dindo classification.Postoperative complications exceeding Grade II in the Clavien-Dindo classification were found in 20 patients(15.3%).No mortalities were observed in this study.LAC can be performed safely for elderly patients older than 70 years.

A 74-year-old man admitted with dysphagia was found to have advanced esophageal squamous cell carcinoma, clinical stage IV (T4N2M0). We initiated definitive chemoradiotherapy(dCRT)with combined 5-fluorouracil and cisplatin chemotherapy( FP therapy)and 50.4 Gy irradiation, followed by boost FP therapy, to which the patient showed confirmed complete response(CR). Local recurrence was detected in the scar of the primary lesion at 4 months after the boost FP therapy. Photodynamic therapy(PDT)for this lesion resulted in CR. Thirteen months later, right hilar and right pericardial lymph node metastases were found. The right hilar lymph node metastases were not visible on CT after triweekly docetaxel therapy, but the pericardial lesions remained. The patient underwent salvage lymphadenectomy without further chemotherapy, and at 5 months after surgery, he was alive and recurrence-free.

We report a case of duodenal liposarcoma. A 62-year-old man presented with an abdominal tumor. Abdominal CT scan and MRI showed a tumor in the wall of the duodenum. Pancreaticoduodenectomy was performed. The final pathological diagnosis was mixed-type liposarcoma. Twenty-one months after the 1st surgery, the patient presented with locoregional recurrence and tumor resection was performed. However, 12 months after the 2nd operation, the patient again presented with locoregional recurrence and further surgery is planned.

The factors which affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after 6 months of treatment. The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level ≤1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014. Forty patients were eligible for the present study. A comparison of the 6-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox’s proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The 6-month continuation rate was 70.8 % in the patients with a CCr ≥60 ml/min and was 25.0 % in patients with a CCr

Endovascular aneurysm repair (EVAR) is used to treat abdominal aortic aneurysms (AAAs) with bilateral common iliac artery aneurysms (CIAAs), and an interruption of the bilateral internal iliac arteries (IIAs) is often needed, which may cause postoperative ischemic complications. An iliac branch device (IBD) has thus been introduced as an endovascular technique to preserve the IIA flow. This study aimed to evaluate the technical feasibility and short-term results of using an IBD when treating AAA with bilateral CIAAs in a Japanese institution, where IBD use has still not been approved by the government. EVAR was performed using an IBD in six patients at high risk for open repair of an AAA with bilateral CIAAs. Advanta V12 stent grafts were successfully placed in the IIA, bridging between the IIA and the IBD side branch from the contralateral iliac artery. Subsequently, EVAR was performed as usual. The technical success rate was 100 %. At the most recent follow-up (mean follow-up period, 14.2 months), all IBDs were patent. No patients complained of buttock claudication or ischemic colitis. The implantation of an IBD during EVAR is technically feasible in Japanese AAA patients with bilateral CIAAs, and may be a viable method to avoid pelvic ischemic complications, such as intractable buttock claudication.

To clarify factors related to vitamin E malabsorption after gastric surgery, we evaluated serum vitamin E levels in patients who had undergone gastrectomy for gastric cancer. We studied 39 patients (26 men, 13 women; mean age, 61.7 years) who underwent gastrectomy for early gastric cancer. Surgical procedures included 24 subtotal gastrectomies and 15 total gastrectomies. We measured serum levels of vitamin E before and 3, 6, 9, and 12 months after gastrectomy. A level of less than 0.75 mg/dl was defined as a low vitamin E level. Serum vitamin E levels decreased to less than 0.75 mg/dl in 6 (15.4 %) of the 39 patients within 6 months after gastrectomy and in 7 (17.9 %) of the 39 patients within 1 year after gastrectomy. The proportion of patients with a low serum vitamin E level was significantly higher in the total gastrectomy group (p = 0.002). A low vitamin E level was significantly associated with a low total cholesterol level. Total cholesterol levels in low vitamin E levels patients were lower than normal vitamin E levels patients. None of the patients with a low vitamin E level had neuropathy. The type of operation performed (total vs. subtotal gastrectomy) may be the major cause of vitamin E malabsorption after gastrectomy for gastric cancer. Vitamin E deficiency probably begins within 6 months after gastrectomy for gastric cancer.

Japanese cuisine has provided satisfying meals by fully utilizing the characteristic aroma and taste of katsuodashi (dried bonito broth), though it is not rich in sugars or fats. Katsuodashi is a very basic and indispensable element in Japanese cuisine, and is a hot water extract of katsuobushi (dried bonito). It has been reported that a dextrin solution containing natural dried bonito broth has a significant reinforcement effect, and has been suggested that the olfactory stimulation is important for the reinforcement effect. We examined various source materials for broth and identified an optimal method of aroma extraction by two-bottle choice and conditioned place preference tests in mice. By two-bottle choice tests, a solution containing arabushi (a type of katsuobushi) aroma extract obtained by a supercritical CO2 extraction method showed a significantly high preference. The conditioned place preference test showed the dashi-taste solution with arabushi supercritical CO2 extract had a reinforcement effect. Our results suggest that the arabushi extract obtained by supercritical CO2 extraction contains components responsible for preference and reinforcement effects in mice; it could become conducive to making Japanese cuisine more satisfying and palatable.

Linalool has two enantiomers, (R)-linalool and (S)-linalool. Both are known to possess several biological activities in stressed animals. Our previous work revealed that inhalation of (R)-linalool altered hypothalamic gene expression in rats under stress. In the present study, we monitored hypothalamic gene expression in restrained rats with and without (S)-linalool inhalation by DNA microarray. The entire gene expression profile showed that inhalation of (S)-linalool significantly changed the expression levels of 316 hypothalamic genes in the restrained rats. The differentially expressed genes (e.g., App, Avp, Igf2, Igfbp2, Sst and Syt5) were found to relate to cell-to-cell signaling and nervous system development. These results indicate that (S)-linalool influences hypothalamic gene expression in restrained rats, and that inhalation of (S)-linalool under the stressed condition has some effects on stress-related biological responses.

ObjectiveTriglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol (CLZ), a selective inhibitor of phosphodiesterase 3, has antiplatelet and vasodilating effects and may decrease serum TG levels. We examined the effect of CLZ on TG accumulation in the arterial tissue of a rat model of carotid artery ligation.MethodsRats were fed normal chow with 0.1% CLZ (CLZ group) or without CLZ (control group) for 4 weeks after unilateral carotid artery ligation near the carotid bifurcation.ResultsAt the end of this period, the control group showed 3.3-fold higher TG levels in the ligated carotid artery than in the contralateral artery; however, compared with the contralateral artery, the ligated artery in the CLZ group showed significantly lower levels of TG accumulation but similar serum levels of TG, total cholesterol, and high-density lipoprotein cholesterol. Furthermore, matrix-assisted laser desorption/ionization imaging mass spectrometry revealed that the ligated carotid artery in both groups had ubiquitous accumulation of TG in the intima, media, and adventitia, along with decreased heme B signals, which was indicative of ischemia. However, heme B signals were less reduced in the CLZ group than in the control group.ConclusionsOur results indicate that CLZ can inhibit the ubiquitous accumulation of TG in arterial tissues, possibly by ameliorating tissue ischemia. CLZ may be useful in improving arterial tissue hemodynamics and lipid metabolism.Clinical RelevanceTriglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol, an antiplatelet and vasodilating drug, has been widely used for patients with peripheral artery occlusive disease to improve intermittent claudication. This study examined the effect of cilostazol on TG accumulation in the arterial tissue of a rat model of carotid artery ligation. We identified a novel effect of cilostazol on inhibition of accumulating TG in the ligated carotid artery tissue. This effect may be expected in clinical use in humans

An unidentified Helicobacter species, strain MIT 01-6451, was frequently detected in mice obtained from domestic commercial and academic institutions in Japan. To partially characterize this strain, its distributions in the gastrointestinal tract and hepatobiliary system of mice were investigated. In gastrointestinal tissues, this strain was detected in all cecum, colon, and feces samples tested, whereas fewer mice were positive in the ileum, jejunum, and duodenum. Interestingly, strain MIT 01-6451 was also detected in most stomach samples and in 33% of gallbladder samples. One mouse was found to be infected with multiple Helicobacter species. Fourteen copies of 16S rRNA genes were cloned from the tissues of this mouse. One had the highest level of sequence homology with H. canadensis, while 13 had the highest level of homology with the H. ganmani type strain or strain MIT 01-6451. Twelve of these 13 16S rRNA genes were mosaic sequences, being partially derived from H. ganmani and strain MIT 01-6451. These results suggest that H. ganmani and Helicobacter sp. MIT 01-6451 are prevalent in specific-pathogen-free mouse colonies in Japan and that lateral gene transfer probably occurs among Helicobacter species during coinfection., Experimental Animals, 62(2), pp.109-116; 2013

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

Most microsurgeons believe that smoking and severity of injury adversely affect the outcome of digital replantation surgery. As countermeasures, several pharmacologic agents have been used for the perioperative period. The purpose of this retrospective study was to examine whether the rate of necrosis is appreciably different across smokers versus nonsmokers with prostaglandin E1 therapy.The authors' study subjects included 144 patients (184 digits) who underwent replantation or revascularization between August of 2013 and August of 2015.The primary outcome was the incidence of total necrosis after replantation surgery, and the secondary outcomes were the rate of overall necrosis, proportion of total necrosis to overall necrosis, and total success. Intravenous administration of prostaglandin E1 was performed at the rate of 120 μg/day for 7 days after surgery in all patients. These outcomes of each injury type were compared between smoking and nonsmoking groups.Among the 184 injured digits, the incidence of total necrosis in smokers (23 percent) was higher than that in nonsmokers (17 percent), although no significant difference was shown (p = 0.36). The adjusted odds ratio was 1.17 (95 percent CI, 0.51 to 2.69). Similarly, there was no significant difference in the secondary outcomes between the two groups.The authors' retrospective study found no significant difference in the formation or extent of necrosis after replantation or revascularization between smoking and nonsmoking groups when all patients were treated with prostaglandin E1.Risk, II.

The patient was an 82-year-old man, who contracted chronic hepatitis C in 1977. In 1997, he was diagnosed with intraductal papillary-mucinous neoplasm (IPMN), and was treated with surgery. In August 2005, cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC) were detected, and he underwent a subsegmentectomy of the liver. In February 2007, he had a supradiaphragmatic lymph node recurrence of CCC. It was a solitary lesion; therefore, we resected the recurrent tumor by thoracoscopic surgery. In January 2012, squamous cell lung cancer was detected and he had a thoracoscopic operation. Furthermore, in February 2015, 2HCCs were detected in S5 and S5/8 of the liver. He underwent radiofrequency ablation. Over the course of 18 years, this patient developed cancers in his pancreas, intrahepatic bile duct, liver, and lung. However, the patient has survived without recurrence because of aggressive therapy and diligent surveillance after surgery.

The aim of this study was to evaluate the safety and feasibility of the bioabsorbable staple line reinforcement in distal pancreatic resection.Thirteen patients underwent distal pancreatic resection using the bioabsorbable staple line reinforcement between May 2014 and December 2014. Surgical complications were evaluated by Clavien-Dindo classification.Median age was 64 years. Median operation time was 219 minutes and median blood loss was 490 mL. ComplicationsGrade 2 were observed in 3 patients. Among them, pancreatic fistula (Grade 2) was found in 2 patients and ileus (Grade 2) in 1. No surgical mortality was observed.Our results may suggest that the bioabsorbable staple line reinforcement is safe and feasible in distal pancreatic resection.

By remarkable progress of chemotherapy for pancreatic cancer, we sometimes achieve resection of initially unresectable pancreatic cancer after chemotherapy. Otherwise, the safety and feasibility of radical pancreatic resection after chemotherapy is not still clear. In this report, we evaluated the safety and feasibility of conversion surgery for initially unresectable pancreatic cancer in our center.Between 2009 and 2014, approximately 500 patients were diagnosed with unresectable pancreatic cancer and received chemotherapy, and after chemotherapy, 10 patients were found to have resectable tumors on computed tomography. We evaluated surgical complications using the Clavien-Dindo classification. Clinicopathological data were reviewed by using UICC, seventh edition, and the chemotherapeutic effect was measured by using Evans classification.The mean age of patients was 68 years, with 4 men and 6 women. The preoperative chemotherapy regimens were S-1 chemotherapy in 2 patients, gemcitabine in 5 patients, and gemcitabine plus S-1 chemotherapy in 3 patients. Nine patients underwent pancreatoduodenectomy, and 1 underwent distal pancreatosplenectomy. The mean operative time was 527.5 minutes, and the mean estimated blood loss was 875 mL. Surgery-related morbidity more than Grade 2 based on Clavien-Dindo classification occurred in 6 patients. Mortality was 0%.Our study suggests that conversion surgery for initially unresectable pancreatic cancer is safe and feasible.

Background To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. Methods Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. Results High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type ( p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion ( p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine ( p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival ( p = 0.007). Conclusion H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose non-fermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.

The dry weight of tendon tissue is accounted for mainly by collagen fibers. Accordingly, the tendon-healing process primarily involves repair of collagen fibers. During the remodeling phase of tendon healing, newly proliferating collagen fibers are transformed into a mature repaired tendon. Despite the importance of this phenomenon, the details of fibrous rebuilding have not been reported previously. The aim of this study was to visualize the ultrastructural changes and to obtain a clear understanding of the reorganization of the collagen fibers in the tendon repair site, using rat Achilles tendons. We used scanning electron microscopy (SEM) with cell maceration as the main method of analysis. Pretreatment with cell maceration removed the cellular components successfully. This allowed precise visualization of each collagen fiber and the three-dimensional network of the fibers. This study was the first to apply the cell-maceration/SEM method to observe tendon tissue. Seven days after surgery, new collagen fibers grew extensively in the repair site in a random arrangement. Fourteen days after surgery, the collagen fibers began to form an axial arrangement. Near the tendon stump, this change progressed from the outer layer to the core region. On the other hand, in the middle of the repair site, it progressed from the core to the outer layer. Change in the axial arrangement of collagen fibers contributes to the connection between the repair site and the tendon stump and to the separation of the repair site from the paratenon.

Objective: Gemcitabine has been widely used, and cisplatin plus gemcitabine is considered as standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard therapy was established following the progression to gemcitabine-containing first-line therapy. As S-1 monotherapy as second-line chemotherapy is still not well known in a practical setting this study aimed to clarify its efficacy and safety. Methods: We retrospectively reviewed 55 consecutive patients who received S-1 monotherapy as second-line chemotherapy after failure of a gemcitabine-containing regimen at our institution from September 2007 to March 2011. The inclusion criteria were preserved organ function and an Eastern Cooperative Oncology Group performance status of 0‐2 and without massive ascites or pleural effusion. S-1 was administered orally twice a day at a dose of 40 mg/m 2 for 28 days, followed by 14 days of rest. Results: Fifty-one patients were selected for this analysis. The overall response rate was 4.0% and the disease control rate was 38.0%. The median survival time was 6.0 months and the median progression-free survival was 2.3 months. Adverse events were generally mild, and treatment-related death did not occur. In the subgroup analysis, overall survival was significantly shorter in the patients with peritoneal dissemination and those who had shown no response to the first-line chemotherapy (P ¼ 0.033 and 0.023, respectively). Conclusions: S-1 monotherapy as the second-line chemotherapy for patients with gemcitabine-refractory advanced biliary tract cancer is also feasible in a practical setting and its efficacy is almost the same as in the previous prospective study.

ObjectiveRecent studies suggest that biologic changes in the vein wall associated with varicose veins (VVs) occur not only in valvular tissue but also in nonvalvular regions. We previously used imaging mass spectrometry (IMS) to determine the distribution of lipid molecules in incompetent valve tissue. In this study, we used IMS to analyze incompetent great saphenous veins (GSVs) in patients with varicose vein (VV) to assess the distribution of lipid molecules.MethodsWe obtained GSV tissue from 38 VV patients (50 limbs) who underwent GSV stripping. For the control veins (CV), we obtained GSV samples from 10 patients undergoing infrainguinal bypass with reversed GSV grafting for peripheral artery occlusive disease (10 limbs). Conventional and immunofluorescence staining were performed for histopathologic examination. The total lipid content in the homogenized vein tissue was determined. The localization of each lipid molecule in the vein wall was assessed by IMS.ResultsThe histologic examination showed the VV walls were significantly thicker than the CV walls, and only the VV adventitia was positive for lipid staining. The VV wall had higher concentrations of phospholipids and triglycerides than the CV wall. IMS revealed an abnormal accumulation of lysophosphatidylcholine (LPC; 1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the VV intima and media. Triglyceride was found only in VV adventitia. The number of lymphatic vessels, as measured by staining with D2-40, a lymphatic vessel-specific marker, was significantly lower in the VV adventitia than in the CV adventitia. Lymphatic vessel reduction may be associated with insufficient lymphatic drainage in the VV adventitia causing histologic changes in VV tissue.ConclusionsThe accumulation of LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) in the VV intima and media may be associated with chronic inflammation, leading to VV tissue degeneration. Furthermore, insufficient lipid drainage by lymphatic vessel may be responsible for accumulation of lipid molecules and subsequent vein wall degeneration.Clinical RelevanceAbnormal distribution of lipid molecules in varicose vein (VV) tissue in patients at CEAP class C2-3 and C4-5 suggests that VV-associated accumulation of lipid molecules begins in the early clinical stages of the disease and continues through the advanced stages. In particular, the accumulation of both lysophosphatidylcholine (1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the media was significantly higher in VV tissue from patients in advanced clinical stages, suggesting an association between lipid accumulation and chronic inflammation of skin and subcutaneous tissues. Further study is needed to clarify the effect of lymph stasis on VVs and chronic inflammation. The mechanism whereby adventitial lymphatic vessels are damaged is also unknown. Consistent venous hypertension and subsequent overload to the lymphatics may account for the lymphatic damage. In addition, accumulation of possible proinflammatory lipid molecules in VV walls may further damage the adventitial lymphatic vessels.