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In several primates and carnivores, pronation/supination angles of the forearm skeleton were examined, and it is thought that a larger angle is useful to acquire dexterous behaviors in feeding and/or life style, including climbing. In this study, the pronation/supination angles in Asiatic black, brown and polar bears were nondestructively examined. These specimens were classified as adult or non-adult. Three or four carcasses of each group of Asiatic black and brown bears were used for CT analysis, whereas only one adult polar bear was used. The forearms were positioned within the gantry of a CT scanner in both maximally supinated and pronated states. Extracted cross-sectional CT images of two positions were superimposed by overlapping the outlines of each ulna. The centroids of the radii were detected, and then the centroid of each radius and the midpoint of a line which connects between both ends of the surface of each radius facing the ulna, were connected by lines to measure the angle of rotation as an index of pronation/supination. In adult brown and polar bears, the angles were smaller as compared with the other groups (Asiatic black and non-adult brown bears). Asiatic black and non-adult brown bears can climb trees, whereas adult brown bears and polar bears cannot. This suggests that the pronation/supination angle is related to arboreal activity in Ursidae.

Background/aim The prognosis of cholangiolocarcinoma, a rare malignant liver tumor derived from hepatic progenitor or stem cells, is considered relatively good; however, it frequently recurs. We herein present the diagnosis, histological findings, and treatment of cholangiolocarcinoma. Case report A 65-year-old woman with a large liver tumor (70 mm in diameter) was referred. Hepatocellular carcinoma was suspected based on strong early enhancement and delayed washout by enhanced computed tomography. The patient underwent curative left tri-sectionectomy. Histologically, she was diagnosed with pure cholangiolocarcinoma in a slightly fibrous liver. Three metachronous recurrent lesions (all ≤10 mm in diameter) were found between fifteen and twenty months after the initial hepatectomy. One lesion and the remaining two lesions were treated with hepatectomy and radiofrequency ablation, respectively. Two years after the initial diagnosis, she was doing well without recurrence. Conclusion Repeated hepatectomy and radiofrequency ablation might be useful for small intrahepatic recurrences of cholangiolocarcinoma.

Aim To assess the utility of the perioperative use of direct oral anticoagulants for patients with hepatocellular carcinoma (HCC) with cancer-associated thrombosis. Case report An 83-year-old woman was admitted with a solitary HCC (10-cm diameter), as well as with multiple sites of venous thromboembolism and macroscopic portal vein tumor thrombosis. She had appropriate liver function without viral hepatitis, triple-positive tumor markers, and secondary polycythemia. Edoxaban at 30 mg was initiated 10 days before surgery to remove HCC. Complete remission of the pulmonary embolism and stability of the deep vein thrombosis and massive superior mesenteric vein thrombosis were recognized preoperatively. An extended left hepatectomy was successfully performed. To avoid hemorrhage complications, we used intravenous administration of nafamostat mesylate for 2 days, thereafter we restarted edoxaban. Superior mesenteric vein thrombosis resolved 5 months after surgery. Conclusion Perioperative oral administration of edoxaban was useful in multidisciplinary treatment for a patient with advanced HCC with cancer-associated thrombosis.

Background Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. Case report Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. Conclusion We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.

We developed a microelectromechanical-system optical interferometer based on an elastomer nanosheet using a polystyrene-polybutadiene-polystyrene (SBS) triblock copolymer for a suspended membrane as a way to improve the stress sensitivity for surface stress detection. The elastomeric SBS nanosheet provides a low Young’s modulus of 28 ±11 MPa, a large elastic strain of 24 ±12%, and high adhesiveness, of which the surface charge and mechanical property are tunable by layer-by-layer (LbL) deposition of polysaccharides. A freestanding SBS nanosheet can be formed above a microcavity using a dry transfer technique without applying vacuum or high-temperature processes. The maximum deflection associated with molecular adsorption increased by sevenfold compared with a parylene-C-based optical interferometric transducer.

Background Colorectal cancer is the third most commonly diagnosed cancer in both men and women, and one of the more widely recognized preventable cancers. Adenosquamous carcinoma (ASC) of the colon/rectum is an uncommon disease that consists of both glandular and squamous components, and the most common site of ACS is the right and transverse colon. Case report Here, we present the case of a 78-year-old woman, who complained of abdominal pain. Colonoscopy revealed a circumscribed tumor in the ascending colon, and no specific lesion was detected in the other areas of the colon or rectum. ASC (pT3N0M0) was diagnosed from right hemicolectomy specimens. Three months after the first surgery, the serum levels of tumor markers had gradually increased, and a new tumor was subsequently detected in the sigmoid colon 2 months later. The sigmoid lesion was surgically resected and diagnosed as ASC (pT3N3M0). Strong PD-L1 expression was also found in the squamous component. Conclusion To our knowledge, this is the first report of a recurrent sigmoid colon ASC that likely originated from the ascending colon, and PD-L1/PD-1 signaling was likely involved in the immune escape mechanism.

In several primates and carnivores, pronation/supination angles of the forearm skeleton were examined, and it is thought that a larger angle is useful to acquire dexterous behaviors in feeding and/or life style, including climbing. In this study, the pronation/supination angles in Asiatic black, brown and polar bears were nondestructively examined. These specimens were classified as adult or non-adult. Three or four carcasses of each group of Asiatic black and brown bears were used for CT analysis, whereas only one adult polar bear was used. The forearms were positioned within the gantry of a CT scanner in both maximally supinated and pronated states. Extracted cross-sectional CT images of two positions were superimposed by overlapping the outlines of each ulna. The centroids of the radii were detected, and then the centroid of each radius and the midpoint of a line which connects between both ends of the surface of each radius facing the ulna, were connected by lines to measure the angle of rotation as an index of pronation/supination. In adult brown and polar bears, the angles were smaller as compared with the other groups (Asiatic black and non-adult brown bears). Asiatic black and non-adult brown bears can climb trees, whereas adult brown bears and polar bears cannot. This suggests that the pronation/supination angle is related to arboreal activity in Ursidae.

Background Hepatic inflammatory pseudotumor (HIPT) is an uncommon benign tumor-like mass that mimics malignant tumors. Case report A 73-year-old man was admitted with severe epigastric pain and high fever. He had received choledocojejunostomy. Enhanced computed tomography showed a 76 mm, heterogeneous, gradual enhanced low-density mass in the caudate lobe and hyperdense fluid was detected around the mass. Based on the diagnosis of hemorrhage from a hypervascular malignant liver tumor, chemoembolization was conducted. Antibiotics (Meropenem) were administered for 2 weeks, and methylprednisolone (125 mg) was administered twice as a premedication for chemoembolization. After the 2nd chemoembolization, rapid tumor shrinkage was observed and the inflammatory changes gradually disappeared. The tumor was finally diagnosed as fibrohistiocytic type HIPT with an ultrasound-guided percutaneous tumor biopsy. The diameter of the liver tumor decreased to 15 mm and intra-abdominal hemorrhage disappeared in 3 months. Conclusion Development of HIPT can be associated with intra-abdominal hemorrhage.

Multidisciplinary treatment is recommended for the management of patients with advanced hepatocellular carcinoma (HCC). Some operative decollateralization of extrahepatic feeding arteries with laparotomy have been introduced for HCC. We herein newly develop laparoscopic devascularization (LDEV) to continue transarterial chemoembolization (TACE) for HCC with extrahepatic collateral arteries. A 74-year-old man with multiple huge HCC (4 tumors, 18 cm in diameter) and poor liver function (non-alcoholic steatohepatitis, Child–Pugh score 7) was treated with 6 times of chemoembolization in combination with LDEV, 3 times of ablation therapies, and lenvatinib therapy. His tumor markers were triple positive (AFP, 12,906.5 ng/ml; PIVKA-II, 491,743 mAU/ml; AFP-L3, 91.8%) before treatments; however, they all returned to normal limits. Complete response was achieved according to the modified RECIST criteria. Unfortunately, he died 6 months after the final treatment with no recurrence of HCC due to the postoperative complication of primary lung cancer. LDEV is a useful tool to continue effective TACE, and multidisciplinary treatment including chemoembolization and LDEV can cure advanced HCC patients with extrahepatic collaterals and impaired liver function.

Aim Our aim was to confirm the utility of Indocyanine green (ICG) fluorescence imaging for intraoperative detection of adrenal hepatocellular carcinoma (HCC) metastasis. Case report An 83-year-old man with a right adrenal HCC metastasis was admitted after complete remission of primary HCC and a metachronous left adrenal metastasis. He was treated with ICG fluorescence-guided limited resection to preserve adrenal function. ICG was administered intravenously at a dose of 0.5 mg/kg, 6 days before the operation. After removal of the entire suspicious metastatic HCC, ICG fluorescence imaging clearly demonstrated two illuminated lesions. The lesions were separately resected using an energy device. Finally, there were no ICG fluorescent lesions which meant residual tumor. Histopathological examination confirmed adrenal metastasis of moderately differentiated HCC in the initial specimen and the additional resected specimens. Three months after the operation, adrenal function was well preserved without recurrence of HCC. Conclusion ICG fluorescence imaging is essential for complete resection of adrenal HCC metastasis.

Hepatic sclerosed hemangioma is a rare benign liver tumor that originated from hepatic cavernous hemangioma; however, the process of its formation has been unclear. We herein present the patient of a histologically proven hepatic sclerosed hemangioma that showed drastic changes in diagnostic images in a short period. A 56-year-old man was referred to our hospital for the treatment of suspicious hepatocellular carcinoma with hepatitis C, approximately 2 cm in diameter in liver segment 8. Initially, the tumor manifested as early entire enhancement with mildly delayed washout in contrast-enhanced ultrasonography; however, it manifested as continuous peripheral enhancement with the central non-enhanced area after 1 month in various diagnostic images. He completely quit drinking and smoking 1 month preoperatively. No special symptoms and signs were found to suggest tumor ischemia. Anatomical resection of segment 8 was completed. Histological examination confirmed the final diagnosis of common type hepatic sclerosed hemangioma, derived from atypically enhancing cavernous hemangioma. No signs of impaired blood flow were observed in both diagnostic images and histological examination. Sclerosing changes in hepatic cavernous hemangioma may be completed in a relatively short time with no apparent reason.

A 58-year-old man with unresectable sigmoid colon cancer and multiple liver metastases(H2, more than 30)received chemotherapy for 2 years. Subsequently, the patient was diagnosed with stenosis of the primary lesion and 5 bilobar, metastatic tumors. Simultaneous resection was unsuitable because of the performance status and comorbidities of the patient. The first surgery consisted of laparoscopic-assisted sigmoidectomy, laparoscopic microwave coagulation therapy(MCT), and percutaneous radiofrequency ablation(RFA). Percutaneous RFA was additionally performed after 2 months. Since 2 liver metastases(S3 and S8)were inadequately treated, 3 courses of P-mab plus FOLFIRI were administered. Finally, laparoscopic- assisted RFA was performed. Subsequently, serum CEA reduced from 288.3 ng/mL to the normal level. We used fusion imaging US, sonazoid US, laparoscopic convex probe, and ICG fluorescence imaging for ablation therapy. Chemotherapy and ablation therapy using various approaches can control unresectable multiple liver metastases and prolong survival by more than 3 years.

The dexterity of fingers is known to indicate a human health condition; thus, a finger force distribution measurement device measuring finger dexterity, essentially, the force, posture, and movement speed of each finger when holding an object in a vertical position, is essential. In this paper, a finger force distribution measurement system was developed with a load cell built into the thumb sensing part, and with a force sensor calibration function solving the sensor responsiveness issue, toward improving the measurement accuracy. Experiments were performed to verify the effectiveness of the device in measuring the finger force distribution with high accuracy.

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.

Great effort has been paid to decrease blood loss during hepatectomy. Excessive blood loss and/or allogeneic blood transfusion can cause an increased risk of perioperative morbidity and mortality and may lead to a greater risk of early tumor recurrence (1-4). Hepatic steatosis or steatohepatitis is present in 30–50% of patients in the Western countries and can increase blood loss and morbidity in patients undergoing hepatectomy for colorectal liver metastases (5-7). Steatotic livers are hypertrophic and delicate and are therefore more difficult to mobilize or transect compared to nonsteatotic livers.

Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

We developed an elastomer-based Fabry-Perot interferometer with 120–1080 nm gap between a freestanding thin film and a substrate using dry transfer technique. A newly developed elastomeric nanosheet using a polystyrene-polybutadiene-polystyrene triblock copolymer (SBS) provides low Young's modulus of 40 MPa, large elastic strain of 40%, and high adhesiveness. A freestanding SBS nanosheet can be formed by dry transfer technique without vacuum and high temperature processes owing to the high adhesiveness of SBS nanosheet. A minimum gap length of 120 nm with an 80 μm in diameter was achieved. With the pressure change, the freestanding membrane was found to deform with good adhesion between the dry transferred SBS and the substrate.

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A measurement of finger grip strength is important, since the grip strength is related with the condition. A lot of kinds of their relationships have been studied. Some doctors who are finger or hand specialists have various kinds of implicit knowledge regarding finger force. If the finger forces could be measured, it is expected that many useful and novel knowledge would be found. Therefore, this paper describes a new finger force distribution measurement system developed for analyzing those implicit knowledge. Some experiments are performed with using the new developed device, and the effectiveness of the device is verified.

In this paper, a finger force distribution measurement system for hand dexterity is developed, newly. This system consists of a measurement device, wireless communication units and a display unit. Measurement data are expressed on the display of the PC in real time and are stored. The other almost devices for finger force and hand force measure the maximum force. Our developed device measure the each finger force distribution, when a cylinder form thing such as a cup or a pet bottle is brought up. Using the measurement system, each finger force of some subjects that is healthy and young are measured to confirm the function of the device. The validity of the device is verified by the experiments. It is clear that influence of little finger is large and the position of thumb is important in grab motion.

Background Various pathological elbow lesions are often complicated with ulnar neuropathy at the elbow (UNE), although the precise pathology, incidence, and clinical and neurological features of these lesions have not been identified. We therefore investigated elbow pathology and neurological severity in Japanese patients with UNE. Methods The medical records of 457 Japanese UNE patients who were surgically treated among 6 hospitals were retrospectively examined. Eligible patients had UNE diagnosed by physical findings and nerve conduction studies according to the criteria of the American Association of Electrodiagnostic Medicine. The elbows were analyzed with regard to age, gender, occupation, pathology at the elbow, and severity of nerve palsy. Results A total of 398 patients with 413 UNE elbows of a mean age of 63 years (range: 15–87) met the inclusion criteria. UNE elbows were predominantly in male patients (69.0%). Overall, 310 elbows (75.1%) had 1 or more elbow lesions: 238 elbows (76.8%) had a single lesion and 72 elbows (23.3%) had 2 or more lesions. The most common lesion was primary elbow osteoarthritis (EOA) occurring in 54.5% of elbows, followed next by medial elbow ganglion in 8.5% and cubitus valgus in 6.5%. Most elbows with medial elbow ganglion or cubitus valgus were associated with EOA. Entrapment sites were at the cubital tunnel in 84.5%–91.3% of UNE elbows, regardless of an association with elbow lesion. The incidence of McGowan grade III lesion was 50.8% in elbows with primary EOA, which was higher than the 35.0% in elbows with no lesion. Conclusions This study revealed that UNE had various isolated or combined elbow lesions. In Japanese UNE, primary or secondary EOA was found in 62.2% of cases and severe motor weakness was noted in 47.2%. The incidences of EOA and severe ulnar nerve palsy in the Japanese UNE are higher than those in Caucasians. Level of evidence Level IV; Prognostic—Investigating the effect of a patient characteristic on the outcome of a disease; Case series.

In this paper, a dynamometer for measurement of the force of each finger is developed, newly. Four pressure sensors are attached to the grip part of the dynamometer that is a smedley type. And, the developed dynamometer is able to measure the normal grip strength, when the grip strength of each finger is measured. Using the dynamometer, the grip strength of each finger of some subjects that are healthy and young are measured. It is clear that maximum grip strength is obtained by middle finger, and that the finger that obtains second maximum grip strength is different. Moreover, the grip strength of each finger of patients with with the carpal tunnel syndrome are measured. It is clear that the patterns of the patients are similar with the patterns of the implicit knowledge of the medical doctor.

Thermoplastic elastomers are attractive materials because of the drastic changes in their physical properties above and below the glass transition temperature (Tg). In this paper, we report that free-standing polystyrene (PS, Tg: 100 °C) and polystyrene–polybutadiene–polystyrene triblock copolymer (SBS, Tg: −70 °C) thin films with a thickness of hundreds of nanometers were prepared by a gravure coating method. Among the mechanical properties of these thin films determined by bulge testing and tensile testing, the SBS thin films exhibited a much lower elastic modulus (ca. 0.045 GPa, 212 nm thickness) in comparison with the PS thin films (ca. 1.19 GPa, 217 nm thickness). The lower elastic modulus and lower thickness of the SBS thin films resulted in higher conformability and thus higher strength of adhesion to an uneven surface such as an artificial skin model with roughness (Ra = 10.6 μm), even though they both have similar surface energies. By analyzing the mechanical properties of the SBS thin films, the elastic modulus and thickness of the thin films were strongly correlated with their conformability to a rough surface, which thus led to a high adhesive strength. Therefore, the SBS thin films will be useful as coating layers for a variety of materials.

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We developed an elastomer-based Fabry–Perot interferometer with a submicron gap between a freestanding thin film and a substrate by a dry transfer technique. A newly developed elastomeric nanosheet using a polystyrene–polybutadiene–polystyrene triblock copolymer (SBS) provides a low Young's modulus of 40 MPa, a large elastic strain of 38%, and high adhesiveness. A freestanding SBS nanosheet can be formed by a dry transfer technique without vacuum and high-temperature processes owing to the high adhesiveness of SBS nanosheets. With the pressure change, the freestanding nanosheet was found to deform with good adhesion between the dry transferred SBS and the substrate.

A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1619–1627, 2014.

Laparoscopic liver resection (LLR) has become a standard procedure for hepatocellular carcinoma (HCC) as well as liver metastases and other benign and malignant liver tumors (1-3). Numerous cohort studies and their reviews or meta-analyses comparing LLR with open liver resection (OLR) for HCC frequently have serious selection biases in terms of the differences in the size, number, tumor location, and malignancy degree (4-6).

In this study, we fabricated a stretchable freestanding ultrathin sheet based on a polystyrene–polybutadiene–polystyrene (SBS) copolymer with entropy-driven elasticity and evaluated its optomechanical properties. The freestanding SBS sheet had a thickness of 675 nm and a size of 10.4 × 10.4 mm2 on a through hole of a poly(dimethylsiloxane) (PDMS) sheet. The measurement of the reflection spectra of the optical interference peaks of the stretched sheets revealed that the SBS nanosheet had a Poisson’s ratio of 0.5–0.68 for a 38% elastic strain, which is one order of magnitude greater than that of parylene.

Background: The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. Methods: Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated. Results: Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth. Conclusion: The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cisplatin. Everolimus could be a useful anti-cancer drug for patients with OSCC.

This study was undertaken to investigate the age-related differences of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-3 (MMP-3) expression in mouse intervertebral disc (IVD) and to determine whether MMP-3 plays a role in disc degeneration. Expression of MCP-1 and MMP-3 mRNA in mouse IVD was assessed by quantitative PCR. The ability of MCP-1 and MMP-3 expression in IVD to respond to TNF-α or TWEAK stimulation was examined by quantitative PCR, WB, ELISA, and immunohistochemistry. IVD derived from MMP-3-deficient and wild-type mice were compared using Safranin-O staining and immunohistochemistry. mRNA levels of MCP-1 and MMP-3 in IVD significantly diminished and the ability of MCP-1 or MMP-3 expression to respond to TNF-α or TWEAK stimulation was significantly reduced as age increased. IVD derived from 64-week-old wild-type mice showed clearly diffuse proteoglycan loss by Safranin-O staining and immunohistochemistry compared with younger mice. However, no loss of proteoglycan and typeII collagen were observed in IVD derived from 64-week-old MMP-3-deficient mice. MCP-1 and MMP-3 expression in mouse IVD showed age-related decreases. The response to inflammation in IVD also displayed age-related changes. Therefore, disc degeneration may vary with the patients' age and targeting MMP-3 may be a possible future therapeutic strategy for disc degeneration.

The CellSearch system (Veridex, LLC) is useful for detecting circulating tumor cells (CTCs) in various carcinomas, including colorectal cancer (CRC); however, there are some problems associated with its clinical use. A transcription–reverse transcription concerted reaction (TRC) method, which is a PCR-based technique producing more stable and reliable results, because it is a more simplified process compared with the conventional techniques, has been introduced for detecting micrometastasis in some carcinomas. We aimed to demonstrate the effectiveness of TRC method in the CTC detection. We compared the two methods for the sensitivity for CTC detection using the colon cancer cell line and 42 whole-blood samples from patients with advanced or metastatic CRC. Furthermore, 25 patients with metastatic CRC were enrolled to investigate the correlation between CTC detection and prognosis in both methods. The sensitivity of the TRC method was similar to that of the CellSearch system. The overall survival rate was significantly worse in the patients diagnosed as CTC-positive by the TRC method than in those diagnosed as CTC-negative; this finding was similar to the prognosis indicated by the CellSearch system. However, clinically, the TRC method could detect CTCs more rapidly and at a reduced cost compared with the CellSearch system. The TRC method seems to be a useful alternative to the CellSearch system for clinically detecting CTCs in patients with metastatic CRC.

Background: Despite improvements in the surgical management of esophageal cancer, the prognosis of patients with lymph node metastases is still unsatisfactory. Recently, survival benefit of neoadjuvant or induction chemotherapy for patients with esophageal cancer has been highlighted. Methods: Efficacy and toxicity of induction chemotherapy for esophageal cancer were reviewed. In addition, our experience on modified docetaxel/cisplatin/5-FU (DCF) as induction chemotherapy was also demonstrated. The modified DCF consisted of 60 mg/m2 of docetaxel on day 1, and 350 mg/m2 of 5-FU and 6 mg/m2 of cisplatin on days 1–5. Two courses have been administered as induction chemotherapy in 51 patients with node-positive esophageal cancer. Response was evaluated by RECIST v1.0 and changes in standardized uptake value by 18F-fluorodeoxyglucose positron emission tomography. Results: Induction chemotherapy may be beneficial for node-positive esophageal cancer, although the consensus has not yet been established. A regimen of induction chemotherapy should have a high response rate and cisplatin/5-FU may be underpowered as an induction setting. DCF can be a candidate for the regimen of induction chemotherapy for esophageal cancer, although severe adverse events have been reported. Several modified regimens to reduce the toxicity have been reported. The response rate of our series was 61% and a significant decrease in standardized uptake values was observed after the induction chemotherapy. Although high-grade neutropenia was still observed with this regimen, neither treatment-related death nor delay in the following treatment was observed. Conclusions: Modified DCF can be a regimen of induction chemotherapy for node-positive esophageal cancer because of its high efficacy, although an adequate care for severe neutropenia is needed.

Laparoscopic liver resection (LLR) has become the standard treatment for various tumors of the liver including hepatocellular carcinoma (HCC) (1-3). LLR for liver tumors are considered to possess several perioperative advantages compared with conventional open liver resection (OLR). The Oslo-CoMet is the only randomized-controlled trial (RCT) to provide solid evidence that LLR is safer, less invasive, and cost-effective compared with OLR in patients with colorectal liver metastases (4).

Background and Objectives The aim of this study is to clarify the extent of lymphatic spread of cancer cells using a novel genetic test to examine patients with thoracic esophageal squamous cell carcinoma (ESCC). Methods A total of 35 patients who underwent an esophagectomy with three-field lymph node (LN) dissection were eligible. The regional LN stations were categorized into the cervical (C), recurrent nerve (RN), paraesophageal (PE), tracheo-bronchial (TB), and perigastric (PG) nodes. Lymphatic spread was pathologically diagnosed with Hematoxylin-Eosin (HE) and anti-cytokeratin immunohistochemistry (IHC) staining, and CEA-mRNA expression was examined using the transcription-reverse transcription concerted (TRC) reaction. Results The rates of lymphatic spread with HE, IHC, and TRC were 7.2%, 10.1%, and 55.5%, respectively. The number of CEA-mRNA(+) LN stations significantly correlated with tumor depth, LN metastasis diagnosed by HE, and vascular invasions. CEA-mRNA expression was observed in 42.9%, 94.3%, 77.1%, 80.0%, and 82.9% of C, RN, TB, PE, and PG nodes, respectively. Conclusions The high frequency of CEA-mRNA expression suggests that systemic therapy is necessary in addition to esophagectomy with adequate LN dissection. Conversely, a relatively low frequency of CEA-mRNA expression in the C node does not support the routine dissection of the LNs in this area. J. Surg. Oncol. 2010;102:509–515. © 2010 Wiley-Liss, Inc.

Helium depth profiling in silicon was investigated by high-resolution elastic recoil detection analysis (HERDA) using a high-resolution Rutherford backscattering spectrometry system. A 0.7 μm Mylar film was installed in front of the detector of this system to eliminate the background signals originating from incident nitrogen ions scattered at the sample surface. This film successfully eliminated the background signals without the loss of helium signals or serious degradation of the depth resolution. The HERDA has several attractive features for helium depth profiling in silicon, including high sensitivity (detection limit of 1 at. % or less), excellent depth resolution (less than 1 nm), and good quantitative accuracy, giving it significant advantages over other surface analysis methods such as secondary ion mass spectrometry.

Peritoneal dissemination of gastric cancer is often refractory to systemic therapies. Although adenoviral gene therapy has been reported to be a potentially useful therapeutic modality, the adenovirus itself has a dose-limiting toxicity. A novel system was constructed using adenoviral oncolytic suicide gene therapy targeting carcinoembryonic antigen (CEA), and its therapeutic effect and the possibility to reduce the total viral dose while still preserving the antitumor effect were assessed.Three types of adenoviruses were prepared for this novel system: (A) Ad/CEA-Cre, (B) Ad/lox-CD::UPRT for a Cre/loxP system, and (C) Ad/CEA-E1 for conditionally replicating adenovirus. The antitumor effect of the oncolytic suicide gene therapy (A + B + C) was then evaluated in vitro. Mice bearing peritoneal dissemination of human gastric cancer were treated with either this system (A + B + C) or with a tenfold viral dose of suicide gene therapy (A + B). The adverse effects in terms of hepatotoxicity were then evaluated between the two groups.The current system (A + B + C) demonstrated significantly better cytotoxic effect for CEA-producing cell lines than did suicide gene therapy (A + B) at the same viral dose in vitro. The effect of oncolytic suicide gene therapy was almost equal to that of the tenfold viral dose of suicide gene therapy in vivo. The hepatotoxicity of the two treated groups was also found to be equivalent.It was possible to reduce the total adenoviral dose of oncolytic suicide gene therapy while still preserving the antitumor effect.

症例は86歳の男性で, 下血を主訴に精査を行い, 直腸内腔全体を占める全周性のRb直腸癌と診断された. 手術前の検討では肛門機能温存が不可能な低位直腸癌と診断され, 腹会陰式直腸切断術が予定されたが, 手術中に直腸癌による腸重積が判明し, これを解除することにより超低位前方切除術を行うことができた. 下部直腸癌で内腔全体を占める腫瘍の場合, 直腸癌による腸重積を考慮に入れ, 慎重な術式の選択をする必要があることが示唆された. 直腸癌による腸重積は極めてまれであり, 若干の文献的考察を加え報告する.

We developed a stretchable freestanding ultra-thin sheet composed by poly(styrene-butadiene-styrene) (SBS) and evaluated its optomechanical properties. The freestanding SBS sheet with a thickness of 675 nm was formed above a through hole of a PDMS sheet. Deflection of the freestanding sheet with a size of 10.4 mm × 10.4 mm was found to be 50 nm by optical surface profiler. In evaluation of the sheet stretch measured by reflection spectra of a thin-film interference peak, SBS nanosheet revealed about 38% of elastic strain. This result demonstrated that the SBS nanosheet is stretchable even though its thickness is one order magnitude of thinner than PDMS.

Surgical resection is the most effective therapy for colorectal liver metastases, subsequently there are chemotherapy and thermal destruction technique using microwave coagulation therapy (MCT) and radiofrequency ablation therapy (RFA). As the surgical approach is generally guided by these criteria (cancer factors : Tumor staging, differentiation of tumor, recurrence free interval, node status and transition of CEA. patient factors : age, liver function and performance status) and these criteria are intricated, the majority of patients present practically with unresectable. The thermal destructive therapy is well acceptable for hepatocellular cancer but not for colorectal liver metastases. We review the patients of colorectal liver metastases that we performed the thermal destructive therapy.

Objective Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension. Methods Forty-seven uncontrolled hypertensive patients who had previously been treated with anti-hypertensive drugs were examined retrospectively. Thirty-two patients received add-on therapy consisting of eplerenone (Group E) and 15 patients received add-on therapy with a Calcium channel blocker (CCB) or an increased dose of CCB (Group C) in addition to their baseline medications. Both the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly decreased at two and 12 months in Group C. In contrast, neither the SBP nor DBP values were significantly changed at two months and eventually decreased at 12 months in Group E. The degree of arterial stiffness, as evaluated according to the cardio-ankle vascular index (CAVI), did not improve at either two or 12 months in Group C, whereas the CAVI values improved as early as at two months and the improvement was sustained at 12 months in Group E. The extent of change in the CAVI was not associated with the level of changes in the SBP or DBP values in Group E. Conclusion Treatment with eplerenone added to the patient's baseline medications improves the degree of arterial stiffness as early as at two months after the beginning of treatment, independent of the blood pressure-lowering actions of these drugs in patients with uncontrolled hypertension.

Thrombin (coagulation factor IIa) is a serine protease encoded by the F2 gene. Pro-thrombin (coagulation factor II) is cut to generate thrombin in the coagulation cascade that results in a reduction of blood loss. Procoagulant states that lead to activation of thrombin are common in bone fracture sites. However, its physiological roles and relationship with osteoblasts in bone fractures are largely unknown. We herein report various effects of thrombin on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed proteinase-activated receptor 1 (PAR1), also known as the coagulation factor II receptor. They also produced monocyte chemoattractant protein (MCP-1), tissue factor (TF), MCSF and IL-6 upon thrombin stimulation through the PI3K-Akt and MEK-Erk1/2 pathways. Furthermore, MCP-1 obtained from thrombin-stimulated MC3T3-E1 cells induced migration by macrophage RAW264 cells. All these effects of thrombin on MC3T3-E1 cells were abolished by the selective non-peptide thrombin receptor inhibitor SCH79797. We also found that thrombin, PAR-1, MCP-1, TF as well as phosphorylated AKT and p42/44 were significantly expressed at the fracture site of mouse femoral bone. Collectively, thrombin/PAR-1 interaction regulated MCP-1, TF, MCSF and IL-6 production by MC3T3-E1 cells. Furthermore, MCP-1 induced RAW264 cell migration. Thrombin may thus be a novel cytokine that regulates several aspects of osteoblast function and fracture healing.