Risk factors for early recurrence after radical gastrectomy followed by adjuvant chemotherapy for stage II or III gastric cancer: a multicenter, retrospective study.

BACKGROUND: Radical gastrectomy followed by adjuvant chemotherapy is the standard treatment for stage II or III gastric cancer in Asian countries. Early recurrence during or after adjuvant chemotherapy is associated with poor prognosis; however, risk factors for early recurrence remain unclear. METHODS: In this multicenter, retrospective cohort study including six institutions, we evaluated the clinicopathological factors of 553 patients with gastric cancer undergoing gastrectomy followed by adjuvant chemotherapy between 2012 and 2016. Patients were divided into the following groups: early recurrence (recurrence during adjuvant chemotherapy or within 6 months after adjuvant chemotherapy completion) and non-early recurrence, which was further divided into late recurrence and no recurrence. Early-recurrence risk factors were investigated using multivariate Cox proportional hazard model. The chronological changes in the recurrence hazard were also examined for each factor. RESULTS: Early recurrence and late recurrence occurred in 83 (15.0%) and 73 (13.2%) patients, respectively. Based on the Cox proportional hazards model, a postoperative serum carcinoembryonic antigen level of ≥5 ng/mL (hazard ratio: 2.220, 95% confidence interval: 1.089-4.526) and a neutrophil-to-lymphocyte ratio of >1.8 (hazard ratio: 2.408, 95% confidence interval: 1.479-3.92) were identified as independent risk factors of early recurrence, but not late recurrence. The recurrence hazard ratios for neutrophil-to-lymphocyte ratio significantly decreased over time (P < 0.001) and carcinoembryonic antigen also had the same tendency (P = 0.08). CONCLUSIONS: A carcinoembryonic antigen level of ≥5 ng/mL and a neutrophil-to-lymphocyte ratio of >1.8 are predictors of early recurrence after radical gastrectomy and adjuvant chemotherapy for stage II or III gastric cancer.

[A Case of Rectal Neuroendocrine Carcinoma with Iris Metastasis].

A 62-year-old man with anal pain was diagnosed with rectal neuroendocrine carcinoma. There were multiple metastases in the liver, lung, paraaortic lymph node, and bone of the patient. After performing a diverting colostomy, irinotecan and cisplatin were administered. Partial response was obtained after 2 courses, and anal pain improved. However, after 8 courses, multiple skin metastases were found on his back. At the same time, the patient also complained of redness, pain, and impaired vision in the right eye. Iris metastasis was diagnosed clinically by ophthalmologic examination and with contrast- enhanced MRI. Iris metastasis was treated with 5 doses of 4 Gy irradiation, ameliorating the eye symptoms. The patient died of the original disease 13 months after the initial diagnosis; however, multidisciplinary treatment appeared effective for palliating cancer symptoms.

[A Case of Jejunal Cancer Treated by Laparoscopic Partial Jejunectomy].

The patient was a 30s male visited our hospital with the complaints of abdominal pain and melena. The internal medicine physician could not detect the cause of the melena by upper and lower gastrointestinal endoscopy. Although the patient resolved with a fast as conservative management so he left our hospital once, he relapsed nausea and abdominal pain. He visited our department. We performed surgery under a preoperative diagnosis of intestinal obstruction. The histopathological diagnosis was moderate differentiated jejunal adenocarcinoma(Stage ⅡA). At present, 1 year 7 months since surgery, the patient survives although with lymphnode recurrence.

The Synergic Role of Actomyosin Architecture and Biased Detachment in Muscle Energetics: Insights in Cross Bridge Mechanism Beyond the Lever-Arm Swing.

Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here, we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and Monte Carlo simulations based on a model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors' distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate less considered components in the chemo-mechanical energy transduction in muscle.

Magnetic Correlation Engineering in Spin-Sandwiched Layered Magnetic Frameworks.

The insertion of "sandwiched spins" between magnetic layers could efficiently affect the interlayer magnetic correlations, but doing so increases the complexity in the interlayer spin alignment because of competition between the inserted spin-layer interaction JNNI and the interlayer through-space interaction JNNNI if the magnitude of JNNI is of the same order as JNNNI with reciprocal signs of the respective interactions. Herein, systematic tuning of the magnetic phase variations by JNNI and JNNNI in two kinds of metal-variable isostructural series of supramolecular pillared layer magnets [MCp*2 ][{Ru2 II,II (2,3,5,6-F4 CO2 )4 }2 (TCNQ)]⋅2 DCE (M=Co, Fe, Cr; 2,3,5,6-F4 PhCO2 - =2,3,5,6-tetrafluorobenzoate; TCNQ=7,7,8,8-tetracyano-p-quinodimethane; DCE=1,2-dichloroethane) and their DCE-free series, in which [MCp*2 ]+ (Cp*=η5 -C5 Me5 ) species with S=0, 1/2, and 3/2 for M=Co, Fe, Cr, respectively, are sandwiched between ferrimagnetic layers of [{Ru2 }2 (TCNQ)]- , is demonstrated. The results showed that the flexible magnetic natures of these magnets are changeable in dependence on JNNI and JNNNI , as well as on interlayer inserted spins M.

3D Vessel Image Reconstruction by MDCT for Surgical Indication and Timing of Strangulating Small Bowel Obstructions.

BACKGROUND: Patients with strangulating small bowel obstructions (SBOs) can rapidly deteriorate, in condition; therefore, immediate and appropriate diagnosis is required. However, some cases of SBO are difficult to diagnose using axial computed tomography (CT) images alone. The impact of 3D vessel imaging for the diagnosis, surgical indication, and timing of strangulating SBOs was investigated, prospectively. METHODS: Clinical data were collected for 111 strangulating SBOs and 48 simple SBOs from patients receiving surgical interventions from January 2009 to March 2018. The accuracy of preoperative diagnoses for the type of SBO was evaluated. Among 159 patients, 27 underwent contrast-enhanced CT imaging as well as prospectively reconstructed 3D vessel imaging of the superior mesenteric artery, vein, and branches. The concordance rate of operative findings and preoperative diagnoses of the type of SBO were compared between axial CT imaging alone and combination of axial and 3D vessel imaging. RESULTS: Overall concordance rate of diagnosis for the type of SBO by axial imaging was 93.1% and that of strangulating and simple SBOs was 92.8% and 93.8%, respectively. Combined axial and 3D vessel imaging resulted in 100% accuracy of preoperative diagnoses for both types of SBO. In addition, abnormalities could be classified from 3D vessel images as central twists or peripheral twists, and deteriorated vascular flow could also be detected. CONCLUSIONS: The combination of axial imaging and 3D vessel imaging can be used to accurately diagnose SBOs, and this imaging technique may be useful for determining the surgical indication and suitable timing of strangulating SBOs.

The association between the increased performance of laparoscopic colon surgery and a reduced risk of surgical site infection.

PURPOSE: Surgical site infection (SSI) is the most frequently occurring nosocomial infection. Remarkable surgical progress has recently been made in laparoscopic surgery. Therefore, our objective was to investigate the association between increased rates of laparoscopic colon surgery and SSI. METHODS: We retrospectively investigated SSI surveillance data from July 2003 to December 2015. Two university hospitals and 25 university-affiliated hospitals participated in prospective SSI surveillance. Univariate and multivariate analyses were performed to detect significant associations. RESULTS: We investigated 9655 colon surgeries. The year in which surgery was performed was significantly associated with the SSI rate (p = 0.0381). The rate of laparoscopic surgery gradually increased during the study period, and by 2012 it was routinely used for > 50% of colon surgeries. Laparoscopic surgery became a significant factor associated with reduced SSI rates compared with conventional open surgery once the performance rate of laparoscopic surgery reached > 50%. CONCLUSIONS: Increasing rates of laparoscopic colon surgery tended to be associated with a reduction in the SSI risk after surgical treatment of colonic disease. The results of this study might encourage surgeons to view laparoscopic surgical techniques as an evidence-based approach for reducing the risk of SSI.

[The Current Status of Palliative Care for Cancer on a Questionnaire Survey].

We evaluated the current status of palliative care for cancer by questionnaire survey in 34 medical institutions belonging to the Hyogo Society for Oncology of the Colon and Rectum. Although 29 institutions(85%)had palliative care teams, the profiles of team members differed between the institutions. The inclusion rates of psychiatrists, nutritionists, medical social workers, clinical psychologists, and rehabilitation therapists was half or less. Ten institutions had some positive screening systems for objective patients. Consultation from a surgical or medical oncologist to a palliative care doctor was most frequently performed at the end of chemotherapy(46%)but was widely distributed from the beginning of chemotherapy to the period of best supportive care. Most institutes positively adopted surgical palliation and palliative radiotherapy as non-pharmacological options. While palliative care teams were prevalent in this survey, the systematic supply of palliative care may be under development with limited resources.

[A Case of Successful Surgical Treatment for Paraaortic Lymph Nodes Recurrence of Gallbladder Cancer].

Cholecystectomy with gallbladder bed resection and regional lymphadenectomy was performed in a 75-year-old man with advanced gallbladder cancer. Pathological examination revealed adenocarcinoma in the gallbladder with regional lymph node metastases. Cancer recurrence was found in paraaortic lymph nodes behind the duodenum 9 months after the surgery. Although chemotherapy using S-1 was initiated, the lymph nodes remained the same size after 2 courses without any new recurrent regions. Lymphadenectomy was then performed as a curative surgery. The patient has remained alive without recurrence for 46 months after the second surgery.

Magnetic Switching by the In Situ Electrochemical Control of Quasi-Spin-Peierls Singlet States in a Three-Dimensional Spin Lattice Incorporating TTF-TCNQ Salts.

Magnetic phase switching in a coordination polymer is reported, which is demonstrated by combining two processes: (A) the pre-organization of magnetic/redox-active molecules into a framework, and (B) a post-treatment through electrochemical tuning of the pre-organized molecules. A TTF.+ -TCNQ.- salt (TTF=tetrathiafulvalene; TCNQ=7,7,8,8-tetracyano-p-quinodimethane) was incorporated into a three-dimensional framework with paddlewheel-type dimetal(II, II) units ([M2II,II ]; M=Ru with S=1, 1; and Rh with S=0, 2), where the [M2II,II ] and TCNQ.- units form the coordinating framework, and TTF.+ is located in the pores of framework, forming an irregular π-stacking alternating column with the TCNQ.- in the framework. In 1, the spins of [Ru2II,II ] and TCNQ.- units make a magnetic correlation through the framework upon decreasing the temperature from 300 K, which is, however, suddenly suppressed below 137 K (=Td (1)) by the formation of a spin singlet in the TTF.+ -TCNQ.- columns, as seen in the spin-Peierls transition (Td (2)=200 K). This material was incorporated as a cathode in a Li-ion battery (LIB); a long-range ferrimagnetic correlation was formed through the three-dimensional [{Ru2II,II }2 TCNQ]- framework at Tc =78 K in the discharge process. The reversible magnetic phase switching between the non-volatile ferrimagnetic and paramagnetic states, resulting from the local spin tuning of quasi-spin-Peierls singlet, is demonstrated through the discharge/charge cycling of the LIB.

Regulation of NO Uptake in Flexible Ru Dimer Chain Compounds with Highly Electron Donating Dopants.

On-demand design of porous frameworks for selective capture of specific gas molecules, including toxic gas molecules such as nitric oxide (NO), is a very important theme in the research field of molecular porous materials. Herein, we report the achievement of highly selective NO adsorption through chemical doping in a framework (i.e., solid solution approach): the highly electron donating unit [Ru2(o-OMePhCO2)4] (o-OMePhCO2- = o-anisate) was transplanted into the structurally flexible chain framework [Ru2(4-Cl-2-OMePhCO2)4(phz)] (0; 4-Cl-2-OMePhCO2- = 4-chloro-o-anisate and phz = phenazine) to obtain a series of doped compounds, [{Ru2(4-Cl-2-OMePhCO2)4}1-x{Ru2(o-OMePhCO2)4}x(phz)] (x = 0.34, 0.44, 0.52, 0.70, 0.81, 0.87), with [Ru2(o-OMePhCO2)4(phz)] (1) as x = 1. The original compound 1 was made purely from a "highly electron donating unit" but had no adsorption capability for gases because of its nonporosity. Meanwhile, the partial transplant of the electronically advantageous [Ru2(o-OMePhCO2)4] unit with x = 0.34-0.52 in 0 successfully enhanced the selective adsorption capability of NO in an identical structurally flexible framework; an uptake at 95 kPa that was 1.7-3 mol/[Ru2] unit higher than that of the original 0 compound was achieved (121 K). The solid solution approach is an efficient means of designing purposeful porous frameworks.

[A Case of Metachronous Liver Metastases of Gall Bladder Cancer Successfully Treated by Liver Resection].

A 73-year-old woman was diagnosed with gall bladder cancer by contrast enhanced CT images.The tumor was detected at the fundus of the gall bladder and enhanced heterogeneously.She underwent radical cholecystectomy including Japanese D2 lymph node dissection for gall bladder cancer.After 4 courses of oral S-1(80mg/m2 administered for 4 weeks and then stopped for 2 weeks)as adjuvant chemotherapy, a liver metastasis at segment 5 appeared 11 months postoperatively.It showed a ring enhanced tumor on contrast enhanced CT images.FDG accumulated in a similar lesion on PET-CT images.The patient successfully underwent partial hepatectomy of segment 5 of the liver.However, another liver metastasis at segment 7 appeared 5 months after the second operation, but it was resected successfully.The primary lesion and both liver metastases showed similar microscopic appearances.Seven courses of gemcitabine therapy(gemcitabine 1,000mg/m2 once every week for 3 weeks and then stopped for 1 week)were administered as adjuvant chemotherapy.She is now doing well without any sign of recurrence 2 years after the initial operation and 14 months after the secondary liver resection.

Electron-Transferred Donor/Acceptor Ferrimagnet with T(C) = 91 K in a Layered Assembly of Paddlewheel [Ru2] Units and TCNQ.

The donor (D)/acceptor (A) assembly reaction of the paddlewheel-type diruthenium(II,II) complex [Ru2(2,4,6-F3PhCO2)4(THF)2] (2,4,6-F3PhCO2(-) = 2,4,6-trifluorobenzoate; abbreviated hereafter as [Ru2]) with 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) in a p-xylene/CH2Cl2 solvent system led to the formation of a two-dimensional layered compound, [{Ru2(2,4,6-F3PhCO2)4}2(TCNQ)]·2(p-xylene)·2CH2Cl2 (1). As expected from this D/A combination, 1 has a one-electron-transfer ionic state with the D(0.5+)2A(-) formulation. This state formally derives a heterospin state composed of S = 1 for [Ru(II,II)2], S = 3/2 for [Ru(II,III)2](+), and S = ½ for TCNQ(•-), possibly causing intralayer ferrimagnetic spin ordering. Most of these types of compounds have an antiferromagnetic ground state because of the coupling of ferrimagnetically ordered layers in dipole antiferromagnetic interactions. However, 1 became a three-dimensional ferrimagnet with T(C) = 91 K because of the presence of interlayer ferromagnetic interactions.

Magnet design by integration of layer and chain magnetic systems in a π-stacked pillared layer framework.

The control of inter-lattice magnetic interactions is a crucial issue when long-range ordered magnets that are based on low-dimensional magnetic frameworks are designed. A "pillared layer framework (PLF)" model could be an efficient system for this purpose. In this report, A magnet based on a π-stacked PLF with a phase transition temperature of 82 K, which can be increased to 107 K by applying a pressure of 12.5 kbar, is rationally constructed. Two types of low-dimensional magnetic framework systems, an electron donor/acceptor magnetic layer and a charge transfer [FeCp*2](+)TCNQ(.-) columnar magnet ([FeCp*2](+) = decamethylferrocenium; TCNQ = 7,7,8,8-tetracyano-p-quinodimethane), are integrated to fabricate the magnet. This synthetic strategy employing a combination of layers and chains is widely useful not only for magnet design, but also for the creation of multifunctional materials with pores and anisotropic frameworks.

[Locoregional recurrence of HER2-positive breast cancer - treatment after complete remission and long-term clinical benefits].

We report 7 cases of locoregional recurrence in human epidermal growth factor receptor 2 (HER2)-positive breast cancer that we treated. An early complete response (CR) and long-term response was achieved in 5 cases. There were 4 HER2- subtype and 3 Luminal HER2-type cases. Metastasis and recurrence were detected in the residual breast tissue and the supraclavicular, axillary, and parasternal lymph nodes. Chemotherapy consisting of trastuzumab was administered as first-line treatment. A CR was observed 3-4 months after the initiation of therapy in 4 cases, and the time to progression was 27.6- 65.8 months. After achieving a CR, 3 patients terminated treatment and 2 patients continued to take trastuzumab. However, due to adverse effects associated with the chemotherapy, 1 patient changed to endocrine therapy. A second, long-term, CR was achieved in 2 relapsed CR patients by re-challenging with the same chemotherapy regimen. Two patients did not achieve CR and died due to distant metastases. For a better quality of life, it is advisable to continue treatment after a clinical CR for solitary or more complex locoregional recurrences. Following the first-line therapy and a so-called chemoholiday, the patient's disease can be re-challenged using the previously sensitive regimen with careful observation.

[Two cases of radiotherapy-induced sarcoma after breast cancer surgery].

We report 2 cases of radiotherapy-induced sarcoma of the residual breast after breast cancer surgery. In 1 case, the patient was a 64-year-old woman. She underwent breast-conserving surgery and axillary lymph node dissection followed by irradiation to the residual breast in July 2001. A 1.1 × 1.0-cm tumor was noted in the residual breast 7 years 5 months after radiotherapy. An excisional biopsy was performed, and a histological diagnosis of angiosarcoma was made. She died of lung and peritoneal metastases 3 years 2 months after the diagnosis. In the other case, the patient was also 64 years old. She underwent breast-conserving surgery and sentinel lymph node biopsy followed by irradiation to the residual breast in October 2006. A 5.7 × 3.9-cm induration was noted in the residual breast 3 years 5 months after radiotherapy. A core needle biopsy was performed, and a histological diagnosis of sarcoma was made. Mastectomy was performed, and the histological diagnosis was malignant fibrous histiocytoma. She died of chest wall and intrapleural tumor recurrence 3 months after the mastectomy. Although radiotherapy-induced sarcoma is rare, early detection of the tumor in the irradiation area is important, as radiotherapy is often performed for breast cancer patients.

A case of intestinal intussusception with unique hemorrhagic polyps due to AL amyloidosis and excessive anticoagulation.

Most adult intussusceptions are secondary to various pathological conditions that serve as a lead point. Because of their serious nature, intussusceptions often require emergency surgery. We report a surgical case of amyloidosis associated with intussusception, probably due to polypoid protrusions and bleeding tendencies. An 80-year-old man with abdominal pain was suspected of having jejunal intussusception on computed tomography. He had been prescribed warfarin for atrial fibrillation, and excessive anticoagulation was observed with a prolonged prothrombin time/international normalized ratio of 5.44 at presentation. After the excessive anticoagulation was resolved, emergency surgery was performed. The intussuscepted jejunum was resected, and a 7 cm long dark-red pedunculated polyp was identified as the lead point, which was accompanied by multiple small pedunculated polyps. Histopathological examination showed that these were all hemorrhagic polyps. Amyloid depositions were observed in the muscularis mucosae, submucosa, and the walls of the blood vessels. Immunohistochemical analysis revealed immunoglobulin light chain amyloidosis. This case is informative to discuss the clinical sequelae of gastrointestinal amyloid deposition.

[The efficacy of early diagnosis of brain metastasis and systemic treatment after radiotherapy in patients with metastatic breast cancer].

We treated 9 patients diagnosed with brain metastasis from breast cancer. Although 1 patient was initially diagnosed as having Stage IV disease, 5 had Stage I/II early breast cancer. All patients had defined brain metastasis after chemotherapy. Brain metastasis was symptomatic in 7 patients, 4 of whom had brain edema, and asymptomatic in 2 patients. The median survival time from breast cancer metastasis was 23 days for patients who did not receive radiotherapy and 19.6 months for those who received radiotherapy. Among the patients treated with radiotherapy, the median survival time was 4.3 months for patients who did not receive further treatment and 19.7 months for those who received chemotherapy or chemotherapy with trastuzumab. One patient with a solitary brain metastasis underwent stereotactic radiosurgery, and treatment is being continued for 1 of the 2 patients who received systemic therapy after whole-brain radiotherapy and additional stereotactic radiosurgery at recurrence to control brain disease. Systemic treatment after radiotherapy is important for brain metastasis from breast cancer, and early diagnosis of brain metastasis facilitates the use of various available treatments.

[A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

A Programmable DNA Origami Nanospring That Reports Dynamics of Single Integrin Motion, Force Magnitude and Force Orientation in Living Cells.

Mechanical forces are critical for regulating many biological processes such as cell differentiation, proliferation, and death. Probing the continuously changing molecular force through integrin receptors provides insights into the molecular mechanism of rigidity sensing in cells; however, the force information is still limited. Here, we built a coil-shaped DNA origami (DNA nanospring, NS) as a force sensor that reports the dynamic motion of single integrins as well as the magnitude and orientation of the force through integrins in living cells. We monitored the extension with nanometer accuracy and the orientation of the NS linked with a single integrin by the shape of the fluorescence spots. We used acoustic force spectroscopy to estimate the force-extension curve of the NS and determined the force with an ∼10% force error at a broad detectable range from subpicoNewtons (pN) to ∼50 pN. We found single integrins tethered with the NS moved several tens of nanometers, and the contraction and relaxation speeds were load dependent at less than ∼20 pN but robust over ∼20 pN. Fluctuations of the traction force orientation were suppressed with increasing load. Our assay system is a potentially powerful tool for studying mechanosensing at the molecular level.