Search

Patients with Crohn’s disease (CD) are generally known to be at an increased risk of cancer. The anorectal area is the most frequent cancer site in Japanese CD patients. However, the risks are not well defined. The aim of this study was to clarify the clinicopathological characteristics of Japanese CD-associated anorectal carcinoma patients and to explore screening methods for the detection of cancer at earlier stages. A systematic review of case series and reports of Japanese CD-associated anorectal cancer patients published between 1983 and 2016 was conducted. There were 144 cases of cancer arising from anorectal lesions of CD. The median duration from the onset of CD to the cancer diagnosis was approximately 17 (0–39) years. The most prevalent histological type of cancer was mucinous carcinoma (49.3%), and 82.1% of patients were over T3 invasion. There were only 15.6% cases with early stage disease. A total of 82% patients had enhanced symptoms, whereas 56.3% of the early cancer cases had no symptomatic changes. Approximately 90% of cases were diagnosed preoperatively, and almost all early cancer patients were diagnosed with colonoscopy. The 5-year overall survival rate was 35.8%. CD-associated anorectal carcinoma had a poor prognosis due to the advanced stage of the cases and aggressive histological features. As earlier-stage cancer is associated with a better prognosis than advanced stage disease, and it is also typically diagnosed by colonoscopy, surveillance colonoscopy may therefore help to improve the prognosis in cases without any symptomatic changes.

Obesity is a serious global health issue; however, the roles of genetics and epigenetics in the onset and progression of obesity are still not completely understood. The aim of this study was to determine the role of Kdm4b, which belongs to a subfamily of histone demethylases, in adipogenesis and fat metabolism in vivo. We established conditional Kdm4b knockout mice. Inactivation of Kdm4b in adipocytes (K4bKO) induced profound obesity in mice on a high fat diet (HFD). The HFD-fed K4bKO mice exhibited an increased volume of fat mass and higher expression levels of adipogenesis-related genes. In contrast, the genes involved in energy expenditure and mitochondrial functions were down-regulated. Supporting these findings, the energy expenditure of Kdm4b-deficient cells was markedly decreased. In addition, progression of glucose intolerance and hepatic steatosis with hepatocellular damages was observed. These data indicate that Kdm4b is a critical regulator of systemic metabolism via enhancing energy expenditure in adipocytes.

Background Few studies have investigated surgical outcomes following a colectomy in pediatric patients with ulcerative colitis (UC). Purpose This study aimed to determine long‐term outcomes in a large cohort of pediatric patients who underwent proctocolectomy with ileal pouch‐anal anastomosis (IPAA) for UC. Methods Pediatric patients (

Objectives With endoscopic submucosal dissection and laparoscopic surgery, treatment for colorectal neoplasms has become minimally invasive. However, few studies have compared endoscopic submucosal dissection with laparoscopic surgery for colorectal neoplasms, excluding deeply invasive cancer on preoperative diagnosis. Methods We retrospectively reviewed the files of patients who had undergone endoscopic submucosal dissection or laparoscopic surgery for colorectal neoplasms between November 2005 and December 2015. We limited patients who were not suspected preoperatively to have aggressive submucosal invasion >1,000 μm. Results Ninety-five patients underwent endoscopic submucosal dissection and 37 underwent laparoscopic surgery. Cases of endoscopic submucosal dissection tended to involve rectal neoplasms more often than colonic neoplasms, shorter operative times, and shorter lengths of hospital stay compared with laparoscopic surgery. The perforation rate during colonic endoscopic submucosal dissection in the early period (November 2005 to December 2010) and late period (January 2011 to December 2015) was 14.8% and 2.9%, respectively. In all cases of perforation during colonic endoscopic submucosal dissection, the ability to maneuver the endoscope was compromised. Though tumors were larger in patients who underwent rectal endoscopic submucosal dissection compared with colonic endoscopic submucosal dissection, the perforation and postoperative bleeding rates with rectal endoscopic submucosal dissection were both 3.2%. The most common indication for laparoscopic surgery was difficulty performing endoscopic submucosal dissection. Serious complications were rare. Conclusions For colonic neoplasms, laparoscopic surgery should be considered when endoscopic submucosal dissection is technically difficult in the early period. For rectal neoplasms, endoscopic submucosal dissection is desirable even for those of large size.

Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knockin mice for Cbl that express wild-type Cbl in a steady state and inducibly express CblQ367P, a CMML-associated Cbl mutant. CblQ367P mice exhibited sustained proliferation of myelomonocytes, multilineage dysplasia, and splenomegaly, which are the hallmarks of CMML. The phosphatidylinositol 3-kinase (PI3K)-AKT and JAK-STAT pathways were constitutively activated in CblQ367P hematopoietic stem cells, which promoted cell cycle progression and enhanced chemokine-chemokine receptor activity. Gem, a gene encoding a GTPase that is upregulated by CblQ367P, enhanced hematopoietic stem cell activity and induced myeloid cell proliferation. In addition, Evi1, a gene encoding a transcription factor, was found to cooperate with CblQ367P and progress CMML to AML. Furthermore, targeted inhibition for the PI3K-AKT and JAK-STAT pathways efficiently suppressed the proliferative activity of CblQ367P-bearing CMML cells. Our findings provide insights into the molecular mechanisms underlying mutant Cbl-induced CMML and propose a possible molecular targeting therapy for mutant Cbl-carrying CMML patients.

Isoniazid preventative therapy is widely used for latent tuberculosis infection. Isoniazid is highly effective but has many adverse effects, including neuropsychiatric. We describe the case of an 80-year-old woman with mania. She had received isoniazid preventative therapy during steroid treatment for rheumatoid arthritis and organising pneumonia for the previous 5 months. Her mania resolved after discontinuation of isoniazid. Adverse effects of isoniazid should be considered even if a long time has elapsed since the start of administration. Physicians other than infectious disease and respiratory specialists also must be aware of the adverse effects of isoniazid preventative therapy.

This study examined the relationship between the recognition of movement and actual movement during the standing long jump. A total of 11 healthy elementary school children from 10 to 11 years of age participated in this study. Participants conducted standing long jumps (the target movement) after receiving video instruction. They were then tested on their recognition of the target movement according to an image. A total of 12 markers were then attached to each participant to measure the actual movements taken during subsequent performances of the target movement. They were then tested on the recognition of their own movements (a self-evaluation). The results were as follows: maximum shoulder angle was observed prior to each jump; this became successively lower in the image review, actual movement, and self-evaluation procedures. Knee flexion angle successively decreased in the actual, target, self-evaluation, and image movements during the railway crossing procedure. While jumping, the maximum shoulder angle was significantly larger in the target movement than the actual ( P < .01) movement, but the actual movement was significantly lower than the image ( P < .001) and self-evaluation ( P < .001) movements. The angle between the perpendicular from the acromion and the line segment connecting the acromion to the lateral malleolus successively decreased in the target, image, self-evaluation, and actual movements. Thus, there were obvious points at which it was either easier or more difficult for subjects to recognize movements. Points of relative ease and difficulty were also identified during performance of the target movement.

Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. In this study, UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of COMPASS-like and SWI/SNF complexes, played an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient (UtxΔ/Δ) mice exhibited myeloid skewing with dysplasia, extramedullary hematopoiesis, impaired hematopoietic reconstituting ability, and increased susceptibility to leukemia, which are the hallmarks of hematopoietic aging. RNA-sequencing (RNA-seq) analysis revealed that Utx deficiency converted the gene expression profiles of young hematopoietic stem-progenitor cells (HSPCs) to those of aged HSPCs. Utx expression in hematopoietic stem cells declined with age, and UtxΔ/Δ HSPCs exhibited increased expression of an aging-associated marker, accumulation of reactive oxygen species, and impaired repair of DNA double-strand breaks. Pathway and chromatin immunoprecipitation analyses coupled with RNA-seq data indicated that UTX contributed to hematopoietic homeostasis mainly by maintaining the expression of genes downregulated with aging via demethylase-dependent and -independent epigenetic programming. Of note, comparison of pathway changes in UtxΔ/Δ HSPCs, aged muscle stem cells, aged fibroblasts, and aged induced neurons showed substantial overlap, strongly suggesting common aging mechanisms among different tissue stem cells.

A 60s man was diagnosed with unresectable advanced rectal cancer with synchronous solitary liver metastasis. Chemotherapy was administered and the primary tumor shrank immediately. However, he still demonstrated dorsal extension; therefore, chemotherapy was continued for approximately 1 year. After long-term chemotherapy, the primary tumor was deemed to be resectable because the dorsal extension had decreased. We achieved curative resection by performing a primary tumor and liver resection and he has shown no recurrence without adjuvant chemotherapy. Although the primary tumor was initially diagnosed as unresectable, it is important to consider the potential for curative resection after long-term chemotherapy.

A 60s man was diagnosed as having unresectable advanced rectal cancer with swelling of the para-aortic lymph nodes. Chemotherapy was administered, and the primary tumor immediately shrank. He still had para-aortic lymph node swelling; therefore, chemotherapy was continued for approximately 2 years. After long-term chemotherapy, we diagnosed his tumor as resectable because the para-aortic lymph node swelling had shrunk. We achieved curative resection, and he has shown no recurrence without adjuvant chemotherapy. Although chemotherapy is the main treatment for unresectable advanced colorectalcancer, it is important to consider curative resection, as in this case with long-term chemotherapy.

Background In recent years, enteral nutrition has become relatively easy to perform through the penetration of percutaneous endoscopic gastrostomy (PEG). However, there have been reports of complications, such as mispuncture of other organs at the time of performing PEG. Previously, we had constructed a gastrostomy under the laparotomy for difficult PEG cases, and 2 years ago, we introduced laparoscopically assisted PEG. This study aimed to clarify the feasibility and safety of LAPEG for elderly people over 65 years old. Methods We evaluated the perioperative outcomes in 7 elderly patients who underwent LAPEG during these 2 years. In these subjects, the safety of LAPEG was evaluated retrospectively based on the surgical outcomes, perioperative complications, and postoperative course using the clinical archives. Results The subjects' mean age was 81.1 ± 8.03 years. LAPEG was successful in all 7 patients. The median operation time was 38 minutes (range, 31-71 minutes). Intraoperative and postoperative early or late complications from LAPEG were not observed in our cases. Enteral nutrition was commenced 2 days after PEG placement in all cases without complications. Conclusion We summarized the LAPEG cases performed at our institution for the elderly, and have reported its feasibility and safety. The strongest advantage of LAPEG was that it allowed placement of the PEG without any complication under direct observation of the intraperitoneal cavity to confirm the safety of each organ.

Background Solitary adrenal metastasis from colorectal cancer is rare. Adrenal metastasis is usually detected with synchronous multiple metastases in other organs and is, therefore, considered to be unsuitable for surgical resection. The long-term outcomes of patients with solitary adrenal metastasectomy from colorectal cancer have been reported; however, the survival advantage has not been established. We herein report two cases of curative adrenal resection in patients with solitary adrenal metastasis from colorectal cancer who achieved long-term survival of > 9 years without recurrence after surgical resection. Case presentation The first case involved a 71-year-old man who underwent abdominoperineal rectal resection for rectal cancer. Preoperative CT revealed a mass in the right adrenal, which was growing after surgery. After chemotherapy the adrenal mass decreased in size, and adrenalectomy was performed at 8 months after the first surgery. A pathological examination confirmed metastasis from rectal cancer. The patient received adjuvant chemotherapy and is currently alive without recurrence at 9 years after the adrenalectomy. The second case involved a 53-year-old man who underwent sigmoidectomy for sigmoid colon cancer. Four years later, lobectomy was performed for isolated lung metastasis. Twenty months later, PET-CT revealed solitary metastasis in the left adrenal gland and adrenalectomy was performed. A histopathological examination revealed metastatic adenocarcinoma of sigmoid cancer. Postoperative chemotherapy was administered after adrenalectomy and the patient is currently alive and apparently disease-free at more than 9 years after undergoing adrenal metastasectomy. Conclusion Curative resection for solitary adrenal metastasis from colorectal cancer may be beneficial for survival.

The purpose of this study was to investigate the effects of running speed on both ground reaction forces (GRFs) and lower limb kinematics during the deceleration phase of the single-leg stop movement. With 7 male university students participating in this study, each subject accelerated forwards at 3 approach speeds (2.50, 2.75, and 3.00 m·s), and stopped with the right leg landing on the force plate. Kinematic data were recorded from a lateral view using 1 high-speed camera. The result was that all subjects indicated the same stopping pattern, and 3 peaks of the resultant GRF were observed. The first peak (P1) appeared before full foot-ground contact, and the time to peak from initial foot contact to P1 was significantly shorter with increasing approach speeds (p ≤ 0.05). The second (P2) and third (P3) peaks were observed after full foot-ground contact, and the resultant GRF at P3 and the posterior GRF at P2 and P3 were significantly greater with increasing approach speeds (p ≤ 0.05). The hip flexion and the planter flexion angles at each peak were larger with increasing approach speeds (p ≤ 0.05). However, there was no significant difference in the vertical GRF, range of motion, and angular velocity of hip, knee, and ankle joints when comparing different approach speeds. This study suggests that to improve the stop movement strategy under faster approach speeds, it is important to increase the magnitude of posterior GRF and the hip and ankle flexion angles under increasing speeds.

Crohn's disease (CD) is associated with an increased risk of developing colorectal cancer. In particular, cases in which long-term survival is achieved by patients with local recurrence of CD-associated rectal cancer are rare. We report a case in which curative resection was achieved for a 47-year-old man with long-standing CD and locally recurrent rectal cancer. In this case, the patient obtained a long-term survival without recurrence after surgical resection with adjuvant chemotherapy and immunosuppressive therapy. In the management of inflammatory bowel disease patients with cancer, the management of both cancer and inflammatory bowel disease treatment is important for the long-term prognosis.

Background & Aims Patients with Crohn’s disease (CD) can require multiple intestinal operations. We examined time trends and risk factors for reoperation in patients with CD who underwent intestinal surgery, focusing on the effects of post-operative medical treatments. Methods We performed a retrospective analysis of 1871 patients with CD who underwent initial intestinal resection at 10 tertiary care institutions in Japan, with initial operative date after May 1982. We collected data on background characteristics of all patients, including Montreal Classification, smoking status, and medical therapy after surgery (tumor necrosis factor antagonists [anti-TNF agents] or immunomodulators). The primary outcome was requirement for first reoperation. Rate of reoperation was estimated using the Kaplan-Meier method, and risk factors for reoperation were identified using the Cox regression model. Results The overall cumulative 5- and 10-year reoperation rates were 23.4% and 48.0%, respectively. Multivariable analysis revealed that patients who underwent the initial operation after May 2002 had a significantly lower rate of reoperation than patients who were operated on before April 2002 (hazard ratio [HR], 0.72; 95% CI, 0.61–0.86). Preoperative smoking (HR 1.40; 95% CI, 1.18–1.68), perianal disease (HR, 1.50; 95% CI, 1.27–1.77), and ileocolic type of CD (HR, 1.42; 95% CI, 1.20–1.69) were significant risk factors for reoperation. Post-operative use of immunomodulators (HR, 0.60; 95% CI, 0.44–0.81) and anti-TNF therapy (HR, 0.71; 95% CI, 0.57–0.88) significantly reduced the risk. Anti-TNF was effective in the bio-naive subgroup. Conclusions The rate of reoperation in patients with CD significantly decreased after May 2002. Post-operative use of anti-TNF agents might reduce the reoperation rate for bio-naive patients with CD.

Longer term efficacy results in Japanese patients enrolled in PREVAIL demonstrate continued treatment benefit of enzalutamide compared with placebo in men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer., A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population.

Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD. Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital. No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml. Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

In laparoscopic colorectal cancer (Lap-CRC) surgery, determination of a suitable mesentery division line and the appropriate degree of lymphadenectomy by tracing the blood supply is critical. We performed visualization of the lymph and blood flow by laparoscopic indocyanine green (ICG) fluorescence imaging (Lap-IGFI). ICG is injected into the submucosa near the tumor via colonoscopy, and the lymph flow is observed. Intestinal blood flow is evaluated by administering ICG intravenously. For lymph flow, visualization of the main lymph node basin helped to determine the surgical division line for cases in which the blood flow was not completely visualized. Lap-IGFI changed the surgical plan of the lymphadenectomy in 23.5 %. In our experience, the metastatic rate of ICG-positive nodes was 10.0 %, and the metastatic rate of ICG-negative nodes was 5.3 %. Furthermore, there were no metastatic nodes that were ICG negative more than 5 cm from the tumor. For blood flow, the blood flow distribution of the intestinal wall from the last branch of the vasa recta of the anastomotic site was clearly visualized and proved useful in choosing the extent of intestinal resection. Lap-IGFI changed the surgical plan of the extensive intestinal resection in 16.7 %. Lap-IGFI can noninvasively provide detailed lymph and blood flow information and is a useful device to aid in the accurate identification of individual patients’ lymph drainage. This helps dictate adequate lymphadenectomy and the extent of intestinal resection in Lap-CRC surgery.

Objectives To investigate the therapeutic outcomes of neoadjuvant and concurrent androgen-deprivation therapy and intensity-modulated radiation therapy with gold marker implantation for intermediate- and high-risk prostate cancer. Methods This was a retrospective study of 325 patients with intermediate- or high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines who underwent androgen-deprivation therapy and intensity-modulated radiation therapy (76 Gy) after gold marker implantation between 2001 and 2010. Results The 5-year distant metastasis-free survival rate was significantly lower for very high-risk patients than for intermediate- and high-risk patients (82.6% vs 99.4% and 96.5%, respectively; P

This study focused on two-dimensional deformation behavior of sports surfaces. Shock attenuation tests and friction tests are generally performed to assess the vertical and horizontal properties of the sports surfaces, respectively. Although the diagonal impacts are often observed in human activities, these tests treat only the vertical impact test. Therefore two-dimensional impact test device were developed for examining the two-dimensional properties of sport surfaces. In previous studies, we evaluated two-dimensional shock attenuation properties of sports surfaces with the VFR (Vertical Force Reduction) and HFR (Horizontal Force Reduction) values. Additionally, we evaluated vertical and horizontal displacement by two-dimensional impact tests with high-speed video analysis in this study.

Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this study, we reviewed our experience of axitinib as a first-line therapy for mRCC in Japanese patients, focusing on its efficacy and safety. We retrospectively assessed 26 patients treated with axitinib as a first-line therapy for mRCC from July 2010 to July 2014 at Chiba Cancer Center and Kinki University Hospital. Observation period was 24.6 ± 18.3 months. The objective response rate was 50.0%, and the median progression-free survival was 27.5 months. Overall survival was not estimable. Common grade 3 adverse events were hypertension in 19 patients and proteinuria in 5 patients. Axitinib demonstrated significant efficacy as a first-line therapy in Japanese patients with mRCC. Careful monitoring and management of the adverse effects may help to control its toxicities.

Pilocytic astrocytomas are found predominantly in the pediatric population and are extremely rare in elderly patients. We describe a case of pilocytic astrocytoma in an elderly patient who presented with the symptoms of an enlarged tumoral cyst. A 70-year-old woman was found to have an asymptomatic small solid tumor with a cystic component in the right frontal lobe at "Ningen Dock(medical checkup)of the Brain". She was hospitalized and underwent further examinations including cerebral angiography. At that time, she was opposed to undergoing an operation for tumor removal owing to lack of symptoms. Approximately fourteen years later, she presented with dizziness upon posture conversion and recent memory disturbance. Computed tomography scanning revealed an enlarged cyst in the frontal lobe and perifocal edematous changes. Gadolinium-enhanced magnetic resonance imaging partially revealed the solid tumor and cystic capsule. The solid tumor had not enlarged substantially. The cystic fluid was aspirated and the solid tumor was resected via a frontal transcortical approach. The histological diagnosis was pilocytic astrocytoma without malignant features. After surgery, the patient's symptoms improved and additional therapy was not provided. After a year of postoperative follow-up, the size of the cystic lesion has reduced, and no recurrence of the solid tumor has been observed.

Although several complications capable of causing pouch failure may develop after restorative proctocolectomy (RPC) for ulcerative colitis (UC), the incidences and causes are conflicting and vary according to country, race and institution. To avoid pouch failure, this study aimed to evaluate the rate of pouch failure and its risk factors in UC patients over the past decade via a nationwide cohort study. We conducted a retrospective, observational, multicenter study that included 13 institutions in Japan. Patients who underwent RPC between January 2005 and December 2014 were included. The characteristics and backgrounds of the patients before and during surgery and their postoperative courses and complications were reviewed. A total of 2376 patients were evaluated over 6.7 ± 3.5 years of follow-up. Twenty-seven non-functional pouches were observed, and the functional pouch rate was 98.9% after RPC. Anastomotic leakage (odds ratio, 9.1) was selected as a risk factor for a non-functional pouch. The cumulative pouch failure rate was 4.2%/10 years. A change in diagnosis to Crohn’s disease/indeterminate colitis (hazard ratio, 13.2) was identified as an independent risk factor for pouch failure. The significant risk factor for a non-functional pouch was anastomotic leakage. The optimal staged surgical procedure should be selected according to a patient’s condition to avoid anastomotic failure during RPC. Changes in diagnosis after RPC confer a substantial risk of pouch failure. Additional cohort studies are needed to obtain an understanding of the long-standing clinical course of and proper treatment for pouch failure.

We herein report the case of a patient with a cecal cancer with simultaneous liver, spleen, and ovarian metastases as well as peritoneal dissemination who achieved a long-term survival. The patient was a 67-year-old female. Ileocecal resection with partial hepatectomy, splenectomy, simple total hysterectomy, bilateral salpingo-oophorectomy, and resection of the peritoneal dissemination were performed. The final diagnosis was Stage IV (T4a, N1, M1b[H1, P3, OTH]). Adjuvant chemotherapy was administered, but abdominal computed tomography(CT)revealed a metachronous liver metastasis 41 months later. We performed partial hepatectomy, and the patient continued adjuvant chemotherapy. The patient is currently alive and disease-free 30 months after the last operation, 72 months after the initial surgery.

A 66-year-old woman underwent total pelvic exenteration for a pelvic tumor. The pathological diagnosis was sigmoid colon cancer T4b(in the small intestine, uterus, and vagina), N0, M0, Stage II . The patient was treated with XELOX for 6 months as adjuvant chemotherapy and was then treated with IRIS for another 6 months. Brain metastasis developed in the left occipital lobe after 12 months, and she underwent craniotomy and enucleation of the tumor. Liver metastasis and peritoneal dissemination metastasis developed 16 months after her initial diagnosis. The patient underwent re-craniotomy and radiotherapy for recurrence of the brain metastasis 18 months after diagnosis and started taking TAS-102 3 months later. She began treatment with CPT-11 plus panitumumab 24 months after diagnosis, and the dose was increased 9 months later(ie, 35 months after the initial diagnosis). The patient remains alive 42 months after surgery.

A 75-year-old man was diagnosed with sigmoid colon cancer with multiple liver metastases at our hospital in May 2010. He underwent mFOLFOX6 and panitumumab chemotherapy for 6 months. He then underwent sigmoidectomy, lymphadenectomy D3, partial resection of 2 parts of S6, and cholecystectomy in January 2011. However, he underwent partial resection of the liver an additional 4 times in the 5 years followingthe primary operation. Despite multiple liver metastases, he is alive 5 years after the primary operation, havingsurvived 5 hepatectomies for multiple resectable liver metastases.

Supplemental Digital Content is available in the text, Background: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P

Renal cell carcinoma expresses CXCR3 but the function of CXCR3 in renal cell carcinoma has not been clarified. We explored the function of CXCR3 in renal cell carcinoma and investigated CXCR3 regulating factors.We obtained 56 clinical samples of clear cell renal cell carcinoma and corresponding normal renal tissue samples from the surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As renal cell carcinoma cell lines, we used 786-O, ACHN and Caki-1. The expression profiles of CXCR3 and its splice variants were examined. For functional analyses 786-O and interferon-γ inducible 10 kDa protein or IP-10 (CXCL10) were selected as representatives.CXCR3 and its ligands were abundant in renal cell carcinoma samples compared to corresponding normal kidney samples. The CXCR3-A-to-CXCR3-B ratio was 1.5 times higher in renal cell carcinoma samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion, and these effects were inhibited by neutralizing antibody. Phosphorylated RhoA and pro/active matrix metalloproteinase-9 expression was up-regulated by CXCL10 treatment. In clinical samples CXCR3 and CXCR3-A expression was significantly higher in metastatic than in nonmetastatic carcinoma samples. Finally, the expression of CXCR3-A and HIF-1α correlated significantly in clinical samples. In 786-O treatment with CoCl2 up-regulated CXCR3 and HIF-1α expression 4.5 and 2.2-fold, respectively.We determined the association of CXCR3 and renal cell carcinoma metastasis. CXCR3 expression may be regulated by hypoxia.

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.

This study focused on two-dimensional shock attenuation properties of sports surfaces. Shock attenuation tests and friction tests are generally performed to access the vertical and horizontal properties of the sports surfaces, respectively. Although the diagonal impacts are often observed in human activities, these tests treat only the vertical impact test. Therefore two- dimensional impact test device were developed for examining the two-dimensional cushioning characteristics of sport surfaces in previous studies. In this study, the various cushioned and non-cushioned impact tests with various impact angles were examined to calculate the VFR (Vertical Force Reduction) and HFR (Horizontal Force Reduction) values without slippery conditions.

We report a case of local recurrence of cancer after rectal endoscopic submucosal dissection (ESD). A 52-year-old male underwent a curative resection with ESD for rectal intramucosal cancer. Seventy-four months after ESD, surveillance colonoscopy showed an elevated lesion on the ESD scar, suspicious of a recurrence. The patient subsequently underwent a low anterior resection (intersphincteric) with lymph node dissection. Pathology revealed a well-differentiated adenocarcinoma, similar to the ESD specimen. We suspected that the local recurrence was caused by implantation of tumor cells during the ESD, due to surgical manipulation performed with the tumor in an exposed setting for a long period of time.

Objective Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated. Methods A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma. Results Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8–6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130–1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand–foot syndrome (64%) and diarrhea (56%) for axitinib, and hand–foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand–foot syndrome, hypothyroidism and stomatitis. Conclusions Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.