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The long-term outcomes of patients with stroke or transient ischemic attack (TIA) after widespread use of direct oral anticoagulants (DOACs) were investigated. Patients with ischemic stroke or TIA admitted between April 2014 and September 2015 were prospectively enrolled and followed for up to 5 years after the index stroke or TIA. Primary outcome measures were any cause of death and stroke recurrence. A total of 555 consecutive patients (323 men; mean age, 75 years; ischemic stroke, n = 520; TIA, n = 35) were analyzed. The follow-up rate was 93%, and the mean follow-up period was 48 ± 20 months. DOACs accounted for 52% of anticoagulants at discharge. During follow-up, 162 patients died, for cumulative mortality rates of 30% (particularly, 53% in cardioembolism) at 5 years. Recurrent stroke occurred in 90 patients, with cumulative risks of stroke recurrence of 19% at 5 years. The 5-year mortality rate remain even after widespread use of DOACs, and further treatment approaches are warranted.

Differentiated cell nuclei can be reprogrammed after nuclear transfer (NT) to oocytes and the produced NT embryos can give rise to cloned animals. However, development of NT embryos is often hampered by recurrent reprogramming failures, including the incomplete activation of developmental genes, yet specific genes responsible for the arrest of NT embryos are not well understood. Here, we searched for developmentally important genes among the reprogramming-resistant H3K9me3-repressed genes and identified Alyref and Gabpb1 by siRNA screening. Gene knockout of Alyref and Gabpb1 by the CRISPR/Cas9 system resulted in early developmental arrest in mice. Alyref was needed for the proper formation of inner cell mass by regulating Nanog , whereas Gabpb1 deficiency led to apoptosis. The supplement of Alyref and Gabpb1 mRNA supported efficient preimplantation development of cloned embryos. Alyref and Gabpb1 were silenced in NT embryos partially because of the repressed expression of Klf16 by H3K9me3. Thus, our study shows that the H3K9me3-repressed genes contain developmentally required genes, and the incomplete activation of such genes results in preimplantation arrest of cloned embryos., (© 2023 Ihashi et al.)

Background: Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF., Methods: Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge., Results: Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002)., Conclusions: Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The patient was a 78-year-old man. He was transferred to the emergency room presenting with aphasia and right hemiplegia. Head CT and CT angiography demonstrated a narrow territory of early ischemic signs and occlusion of the horizontal segment of the left middle cerebral artery (MCA), respectively. Endovascular thrombectomy was performed and complete recanalization of MCA was achieved. After admission, transthoracic echocardiography revealed a cystic mass near the left coronary apex of the aortic valve, which was diagnosed as an aneurysm of the sinus of Valsalva (ASV) by contrast-enhanced chest computed tomography. Transesophageal echocardiography showed a severe smoke-like echo within ASV, despite being in sinus rhythm. Intravenous anticoagulant therapy was started, and patch closure was performed by cardiovascular surgeons on the 13th day despite of early period after stroke onset. During the operation, no thrombus was seen around the inlet of ASV. On the two days after the operation, paroxysmal atrial fibrillation was detected and anticoagulant therapy was continued. In this patient, ASV was regarded as the embolic source of cerebral embolism, and anticoagulant therapy and surgical intervention were selected in the early period after stroke onset to prevent embolism recurrence, resulting in a favorable clinical course.

A 57-years-old man with a history of bronchial asthma and pansinusitis developed acute progressive muscle weakness and sensory disturbance of the distal limbs after upper respiratory infection. On day 15 after onset of sensory disturbance and muscle weakness, the patient admitted to our hospital. A neurological examination revealed asymmetry weakness of both proximal and distal muscles, "glove and stocking type" hypoesthesia, and paresthesia without obvious pain. Blood tests and a nerve conduction study demonstrated eosinophilia and elevation of MPO-ANCA, axonal multiple mononeuropathy, respectively. The cerebrospinal fluid was normal. Eosinophilic granulomatosis with polyangiitis (EGPA) or Guillain-Barré syndrome (GBS) were suspected. So intravenous immunoglobulin therapy (IVIg) and high dose methylprednisolone pulse therapy (HDMP) followed by oral prednisolone were started. However, neurological symptoms did not improve. Sural nerve biopsy on day 31 revealed varying myelinating fiber loss at every nerve bundle and perivascular lymphocytic infiltration. The results did not fulfill the pathologic criteria for EGPA, but supported the changes of vasculitis. Cyclophosphamide (CPA) pulse therapy was administered for the additional therapy. Neurological symptoms did not improve and worsened again after decreasing oral prednisolone; therefore, combined therapy with IVIg, HDMP, and CPA was administered. Neurological symptoms then diminished gradually and the MPO-ANCA level and number of eosinophils normalized. This case suggests the importance of early nerve biopsy to obtain pathological findings supportive of EGPA diagnosis to allow introduction of aggressive immunosuppressive therapy such as CPA in a case with acute progressive motor-sensory neuropathy due to EGPA mimicking GBS.

The utilisation and fermentation of highly cross-linked phosphate starches made from two different origins, potato (HXL-P) and tapioca (HXL-T) were investigated in rats and humans. HXL-P and HXL-T were highly resistant to digestion by carbohydrate enzymes and were also resistant to fermentation by gut microbiota in rats. The postprandial blood glucose scarcely increased after administration of HXL-P or HXL-T in healthy humans. Incremental AUC of both HXL-P and HXL-T for 180 min was significantly lower than that of glucose ( p  < .05). Breath hydrogen excretion was very low after oral administration of HXL-P or HXL-T, and AUCs of breath hydrogen excretion for 13 h after administration were significantly lower than that of fructooligosaccharide as a reference of fermentation ( p  < .05). These results show that HXL-P and HXL-T were hardly digested and were highly resistant to fermentation. In conclusion, HXL-P and HXL-T could be good low-energy bulking ingredients to replace wheat flour.

An 82-year-old man with advanced lung cancer who had declined aggressive therapy was transferred to our hospital due to sudden-onset consciousness disturbance, global aphasia, and right hemiplegia. An electrocardiogram showed atrial fibrillation, and brain MRI and MRA revealed acute ischemic lesions of the left hemisphere and occlusion of the left internal carotid artery (ICA), respectively. We diagnosed acute ischemic stroke due to left ICA occlusion and performed endovascular thrombectomy, which resulted in complete recanalization of the left ICA after retrieval of the culprit embolus. Pathological examination of the retrieved thrombus revealed the presence of tumor tissue, as well as fibrin or red blood cells. Treatment was continued after admission, but the patient died of respiratory failure on day 40 of hospitalization. Autopsy revealed invasion of the tumor in the pulmonary vein, but not in the wall of the left atrium where thrombi were present. However, pathological examination of these thrombi in the left atrium revealed tumor tissue, along with fibrin or red blood cells. These findings suggest that the wall of the left atrium, in which lung cancer had not invaded, may be an incubator of a mixed embolus containing tumor tissue and thrombi in a case of cerebral embolism associated with both lung cancer and atrial fibrillation.

A 72-year-old man on hemodialysis for 7 years with end-stage renal disease was admitted to our institution due to an acute headache. Physical examination revealed normal signs except for noise on the back of his neck. His head CT and brain MRI showed no abnormal findings, while his MRA demonstrated abnormal signals in the left transverse to sigmoid sinus (T-S) suggesting a left dural arteriovenous fistula. After admission, his headache persisted and left orbital numbness also occurred. His digital subtraction angiography performed on the 5th day after admission showed no vascular malformation of either the T-S or cavernous sinus (CS). However, it showed occlusion of the left brachiocephalic vein (BCV) and the origin of the left internal jugular vein (IJV) resulting in intracranial venous reflux. These findings indicated the possibility that his acute headache was caused by intracranial venous reflux and increase of intracranial pressure resulting from the occlusion of the BCV ipsilateral to a dialysis shunt. Percutaneous transluminal angioplasty (PTA) for occlusion of the left BCV was performed on the 9th day and successful dilation of the lesion with a residual stenotic ratio less than 30 percent was obtained. After the angioplasty, venous reflux to the intracranial vein was markedly reduced and his headache and orbital numbness disappeared. One day after the procedure, MRA demonstrated the disappearance of the abnormal signals of the left T-S. Twelve months after discharge, he felt discomfort in the left of his face and the re-occlusion of the left VCV was demonstrated by angiography, therefore he received re-PTA. We recommend that physicians consider occlusion of the BCV ipsilateral to a dialysis shunt and intracranial venous reflux as a cause of acute headache in patients on hemodialysis.

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis., (© 2020 Chapa-y-Lazo et al.)

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an OTC drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action. Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to the 5-hydroxytryptamine (5HT) 2B receptor in concentration-dependent manner with modest inhibitory effects on monoamine oxidase-A and transient potential vanilloid 1 channel. The 5HT 2B receptor antagonist activity of ETZ was also confirmed in a cellular functional assay. Furthermore, the drug exerted no inhibitory effects on cycrooxygenase-1 and -2. In the rat formalin test, oral administration of ETZ significantly reduced the nociceptive responses of the second phase and also the number of c-Fos-expressing cells in the spinal dorsal horn, in a dose-dependent manner. Moreover, intrathecal administration of ETZ significantly reduced the nociceptive responses. These results suggest that the analgesic effect of ETZ is exerted at least in the spinal cord, and the effect would be attributed to multiple mechanisms of action including 5HT 2B receptor blockade.

A 66-year-old woman was admitted to our institution with sudden-onset weakness of her left upper limb. Neurological examination revealed monoplegia and sensory loss of the limb. A brain MRI did not find evidence of an acute ischemic stroke. Her medical history revealed that she had fallen and bruised her shoulder 3 days earlier. Detailed physiological examination revealed that there was a mild subcutaneous ecchymosis with tenderness in the left shoulder. An additional contrast-enhanced chest CT scan showed a fracture of the clavicle diaphysis and a pooling contrast agent demonstrating a 60*40 mm mass near the left subclavian artery (SUB-A) which suggested a pseudoaneurysm. We determined that her symptoms were due to compression of the brachial plexus by immediate growth of a traumatic SUB-A pseudoaneurysm (TSAP) due to her earlier fall. For reduction of pressure to the brachial plexus by the TSAP and prevention of rupture, an endovascular treatment team performed endovascular internal trapping of the left SUB-A just distal to the orifice of the left vertebral artery and a cardiovascular surgeon performed percutaneous drainage of the pseudoaneurysm. After the procedure, the palsy and sensory loss of the left hand gradually improved. A TSAP could be one of the causes of sudden-onset palsy of the upper limb within a few days after a fall.

A 69-year-old man presented with a history of personality change for several years. He was admitted to our hospital due to partial seizure. A cerebrospinal fluid test and an electroencephalogram showed no specific abnormalities, but brain magnetic resonance imaging revealed abnormal findings in the right temporal pole, bilateral amygdala to hippocampus, and insular cortex. He was diagnosed with limbic encephalitis accompanied by partial seizure, and received infusion of an antiepileptic agent and acyclovir. Additional examinations for malignancy and autoimmune disease were performed, and neck CT and MRI revealed a neck tumor. Neck lymph node biopsy suggested lymph node metastasis of a neuroendocrine neoplasm derived from other organs. He did not want aggressive treatment involving surgical resection and chemotherapy, and thus, conservative treatment was chosen by an otorhinolaryngologist and immunotherapy was not used. After discharge, the neck tumor grew gradually. To manage the focal mass effect, chemotherapy and surgical resection followed by chemoradiotherapy were performed by the otorhinolaryngologist on days 244 and 325 of the disease course, respectively. Histology of resected tissues disclosed neck neuroendocrine carcinoma derived from a submandibular gland. His personality change improved temporarily after surgical resection, but then worsened again with regrowth of the tumor. He died on day 723. After death, a blood test revealed the presence of anti-amphiphysin antibody. This case suggests that neck neuroendocrine carcinoma can induce paraneoplastic limbic encephalitis, and in such cases, early surgical resection of the neck tumor with suspected lymph node metastasis is necessary both to control symptoms associated with encephalitis and to exclude carcinoma derived from the neck itself.

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m 2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m 2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We experienced 2 cases of pelvic recurrence from rectal cancer. These patients received radiofrequency ablation(RFA) therapy. Case 1 was a 76-year-old man who underwent intersphincteric resection for lower rectal cancer in October 2013. In May 2015, the patient received systemic chemotherapy for multiple lung metastases and pelvic local recurrence. In January 2017, RFA was performed to reduce the pain of the pelvic recurrence. Immediately after RFA, the pain markedly reduced, and 2 months after treatment, the patient discontinued his pain therapy. Case 2 was a 48-year-old man who underwent Hartmann 's procedure for ulcerative colitis with rectal cancer in November 2011. In July 2012, we performed abdominoperineal resection for rectal cancer that developed in the remnant rectum. In November 2012, he received systemic chemotherapy for multiple lung metastases and pelvic recurrence. In addition, we performed stereotactic radiotherapy(SRT)for the pelvic recurrence. In May 2016, because he developed bilateral hydronephrosis and painful pelvic recurrence, we performed bilateral nephrostomy and RFA for the painful pelvic recurrence. After RFA, pain reduced, but he developed a pelvic abscess that was treated by CT-guided drainage. He underwent complete ablation for the recurrent pelvic mass 2 years after RFA but died of exacerbation of multiple lung metastases. CT-guided RFA for painful pelvic recurrence from rectal cancer can be considered a feasible and effective treatment to reduce pain.

Introduction: The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up., Methods: We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC., Results: The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC)., Conclusions: The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

A 61-year-old man was admitted to our institution with progressive hypoacusia, double vision, and lightheadedness. Neurological examination on day 6 of his illness showed severe hypoacusia, mild confusion, ocular motility disorder, truncal ataxia and absence of a deep tendon reflex. MRI fluid-attenuated inversion recovery imaging revealed symmetrical high intensities in the tectum of the midbrain, involving the bilateral inferior colliculi and the bilateral medial thalami, which suggested Wernicke encephalopathy (WE). Thiamine was administered immediately after completion of the MRI, and the patients' hearing and other abnormal neurologic signs improved rapidly within a few days, except for the absence of the deep tendon reflex. Whole blood examination at admission revealed very low levels of vitamin B1. The patient was discharged on day 19, and MRI on day 39 showed the disappearance of the abnormal high intensities involving the bilateral inferior colliculi. The present case indicates that hypoacusia and abnormal MRI signal due to WE might be normalized by administration of thiamine a few days after the onset of symptoms.

A 67-year-old woman was diagnosed with cecal cancer, para-aortic lymph node metastasis, peritoneum dissemination, and left breast cancer. We administered mFOLFOX6 plus panitumumab for cecal cancer and an aromatase inhibitor for her breast cancer. She received 7 courses of systemic chemotherapy and showed a partial response. She additionally received 5 courses of mFOLFOX6 plus panitumumab. We performed ileocecal resection, sigmoidectomy, right oophorectomy, dissection of the para-aortic lymph nodes, and peritoneal dissemination. The histopathological findings revealed adenocarcinoma, ypT3, ypN0, ycM0, ypStage II (therapeutic effect Grade 2). One month later, she underwent an enforced left breast segmental resection and sentinel lymph node biopsy(0/2). The results of the pathological examination indicated no residual cancers (therapeutic effect Grade 3). The patient is now in good health and was administered S-1 as an outpatient.

Case 1: 63-year-old woman received abdominoperineal resection with lateral lymph node dissection for rectal cancer in 2008. After adjuvant chemotherapy, she suffered from lung metastasis and received partial pneumonectomy in 2012. However, chemotherapy was performed again for lung metastasis and mediastinal lymph nodes in 2013. Radiofrequency ablation (RFA)was performed to lung metastasis in 2016 due to ineffectiveness of chemotherapy. Case 2: 81-year-old man received Hartmann's procedure for rectal cancer with lung and liver metastasis in 2012. After 6 months of chemotherapy, liver partial resection and pulmonary partial resection were performed. In spite of additional chemotherapy, He received partial pneumonectomy in 2013. In 2014, he restart chemotherapy due to lung metastasis. In 2016, he received RFA for lung metastasis because of ineffectiveness of chemotherapy. After that, he received g-knife for brain metastasis. He is going to receive RFA for another lung metastasis.

We had 2 cases of liver-limited and unresectable liver metastases from colorectal cancer with RAS mutations. These patients received hepatic arterial infusion chemotherapy(HAI), finally achieving pCR. Case 1 was a 76-year-old female with rectosigmoid cancer and multiple liver metastases. We underwent anterior resection for primary lesion. After surgery, the patient had received first-line and second-line systemic chemotherapy for the multiple liver metastases. The patient achieved SD and had Grade 3 neutropenia. We then performed HAI as third-line chemotherapy and we therefore underwent hepatectomy. The results of the pathological examination after hepatectomy pCR and is currently alive without cancer recurrence for 61 months. Case 2 was a 53-year-old male with sigmoid colon cancer and multiple liver metastases. We underwent sigmoidectomy with laparoscopic assistance. Three months after surgery, we underwent resection of the lateral segment of the liver under laparoscopy. This patient had cancer recurrence in the remnant liver at 6 months after surgery and had received first-line systemic chemotherapy. The patient had Grade 3 neutropenia after 1 course of chemotherapy and showed no improvement. We then performed HAI as second-line chemotherapy, and we therefore underwent hepatectomy. The results of the pathological examination after hepatectomy were pCR and he is currently alive without cancer recurrence for 30 months.

Background: Adjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide., Patients and Methods: We assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis., Results: The number of patients aged <64, 65-74 and >75 years was 2007 (44%), 1614 (35%) and 977 (21%), respectively. Tumour location, tumour marker positivity, clinical stage, performance of adjuvant therapy, CS and overall survival (OS) were significantly different among these age groups (P < 0.0001). Among patients aged ≥75 years with stage III CRC, 35% with colon cancer and 21% with rectal cancer received adjuvant therapy; these proportions were much lower than those in younger patients. Application of adjuvant therapy was dependent on the CS in patients aged ≤74 years, but not in older patients. Sex, the carcinoembryonic antigen concentration and adjuvant therapy were significantly associated with OS in elderly patients with stage III CRC., Conclusion: Age and comorbidities worsened the OS of patients with CRC who underwent curative surgery. However, patients aged ≥75 years were undertreated regardless of their CS despite the possibility of OS improvement by adjuvant therapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research. One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. The DCCHs performed better with regard to usage of Japan Society of Colorectal Cancer Research guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011-2015, which is fewer than the number expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was carried out in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more surgery than non-DCCH departments, although most of the management, including surgical procedures and use of non-steroidal anti-inflammatory drugs, was similar. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Computational prediction of compound-protein interactions (CPIs) is of great importance for drug design as the first step in in-silico screening. We previously proposed chemical genomics-based virtual screening (CGBVS), which predicts CPIs by using a support vector machine (SVM). However, the CGBVS has problems when training using more than a million datasets of CPIs since SVMs require an exponential increase in the calculation time and computer memory. To solve this problem, we propose the CGBVS-DNN, in which we use deep neural networks, a kind of deep learning technique, instead of the SVM. Deep learning does not require learning all input data at once because the network can be trained with small mini-batches. Experimental results show that the CGBVS-DNN outperformed the original CGBVS with a quarter million CPIs. Results of cross-validation show that the accuracy of the CGBVS-DNN reaches up to 98.2 % (σ<0.01) with 4 million CPIs., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes., Methods: Between January 2008 and December 2014, 54 consecutive patients with T3-4, N0-2, M0-1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6-8 weeks after CRT. We assessed malnutrition after completion of CRT (5-6 weeks after CRT start date) and at surgery (11-14 weeks after CRT start date), defining weight loss as ≥5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone., Results: Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1-3 patients., Conclusion: Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT., Competing Interests: Compliance with ethical standards Informed consent was obtained from all included patients and the Medical Ethics Committee of the hospital approved this study.

Background: Extramural tumor deposits (TDs) and extracapsular lymph node involvement (ECLNI) are considered to be poor prognostic factors in patients with T3-4, N0-2, M0 colorectal cancer (CRC). Although TDs are known to have multiple origins and pleomorphic features, the prognostic significances of the different type of TDs have not yet been established., Methods: We performed a retrospective review of 385 consecutive patients with T3-4, N0-2, M0 CRC who received curative resection at our institution between 2006 and 2012. We classified the TDs into two groups: invasive-type TD (iTD), which is characterized by the presence of lymphatic invasion, vascular invasion, perineural invasion, or undefined cancer cell clusters and nodular-type TD (nTD), which is characterized by a smooth or irregular-shaped tumor nodule other than an iTD. ECLNI was defined as invasion of cancer cells into capsular collagen tissues or adipose tissues beyond the capsular collagen. Multivariate analyses were used to assess the prognostic significance of iTD, ND, and ECLNI for relapse-free survival (RFS), disease-specific survival (DSS), and sites of recurrence., Results: In patients without lymph node (LN) metastasis, the incidences of iTD and nTD were both in the range of 2-3 %. Conversely, in patients with LN metastasis, the incidences of iTD, nTD, and ECLNI were 31, 22, and 34 %, respectively. iTD, nTD, and ECLNI were all significant independent adverse factors for RFS in rectal cancer, and were all associated with pT, pN, and LN ratio. iTD was a significant independent adverse prognostic factor for DSS in rectal cancer, metastasis to the liver in colorectal cancer, and distant LN metastasis in colon cancer. ECLNI was a significant independent prognostic factor for RFS in colon cancer., Conclusions: Classifying TDs and assessing ECLNI may help establish significant prognostic factors for patients with T3-4, N0-2, M0 CRC.

A 49-year-old woman was admitted to our hospital with gradually progressive weakness of the limbs for about 20 days. She presented with weakness of the limbs, predominantly in the proximal portion, and slight dysesthesia of the limbs, predominantly in the distal portion. Repeated nerve conduction examination revealed axonopathy dominantly in the motor neurons. Therefore, we suspected her as having Guillain-Barré syndrome, and initiated intravenous administration of high-dose immunoglobulin. However, her symptoms progressed gradually and finally she found it difficult to walk. Her urine analysis simultaneously demonstrated albuminuria, and a kidney biopsy indicated focal segmental glomerulosclerosis. At that point, laboratory examination showed high levels of anti SS-A antibody and salivary gland biopsy revealed infiltration of a significant number of lymphocytes around the gland, which led to the diagnosis of Sjögren's syndrome. We considered the etiology of the neural and renal dysfunction as due to the inflammatory mechanism associated with Sjögren's syndrome. Therefore, we administered a second course of immunoglobulin therapy and steroid therapy, which included both pulse and oral administration. Her neurologic symptoms and albuminuria improved rapidly after steroid therapy. The present case indicates that both motor dominant neuropathy and focal segmental glomerulosclerosis can occur in patients with Sjögren's syndrome.

A 64-year old woman was admitted to our hospital with subacute onset paraparesis and sensory disturbance at a level below Th10. Spinal MRI showed a T2 weighted high-signal intensity lesion at a level from Th5 to Th12, and an abdominal CT showed a mass in the left kidney. Her paraparesis deteriorated rapidly, and administration of high dose methyl prednisolone followed by oral steroid therapy was started before obtaining of a definitive diagnosis. However her symptoms did not improve after the beginning of treatment. At the same time, a bone marrow puncture, and biopsies from kidney and spinal cord were performed. These biopsies demonstrated no clues, diagnostically. Therefore a random skin biopsy was performed at the five sites on the 17th day after the steroid dosage end. From this, pathological evidence of intravascular large B cell lymphoma (IVLBCL) was shown. For rapid diagnosis of acute myelopathy with mass lesion of another organ due to IVLBCL, a biopsy is taken not only from spinal cord or mass lesions, but is also taken of multiple sites in skin randomly. This must be performed without a delay before a sudden deterioration of neurologic symptoms can occur from ischemic events not responsive to steroid therapy.

In the EMBRACE trial, eribulin was reported to significantly increase overall survival compared to treatment of the physician 's choice when given to patients with recurrent or metastatic breast cancer who had received prior treatment, including an anthracycline and a taxane. In April 2011, eribulin was approved in Japan for the treatment of inoperable or recurrent breast cancer. In this article, we report on the efficacy and safety of eribulin in cases we encountered. Twenty patients with advanced and recurrent breast cancer were administered eribulin in our hospital during the period from August 2011 to December 2012. The median age was 62 years(range, 42-76 years); 16 patients had the estrogen receptor(ER)(+)/human epidermal growth factor receptor 2(HER2)(-)subtype, whereas 4 patients had the triple-negative subtype. Following recurrence, the median number of chemotherapy regimens was 3(range, 0-5). Regarding the antitumor effects of eribulin, no cases showed complete response(CR), 5 cases showed partial response(PR), and 10 cases showed stable disease(SD); therefore, the response rate(CR+PR)was 25% and the clinical benefit rate(CR+PR+B6-month SD)was 35%. Median progression free survival was 146 days, and median overall survival was 482 days. In terms of adverse events(AEs), observed cases of hematotoxicity were of neutropenia(75%), leucopenia(75%), and anemia(80%). Cases of Grade 3 hematotoxicity or higher were of neutropenia(40%), leucopenia(20%), and febrile neutropenia(1 case, 5%). The observed non-hematotoxic AEs were peripheral neuropathy(30%)and general malaise(35%), although none were of Grade 3 or higher. The therapeutic efficacy of eribulin in the present study was relatively better than that in previous reports(EMBRACE trial, Japan Domestic 221 trial). The frequency of Grade 3 or higher AEs was low, and the drug was well tolerated. We believe that eribulin is a novel drug that provides therapeutic efficacy while maintaining quality of life(QOL).

Emergency neuroendovascular revascularization is a reperfusion therapy for acute stroke. The operator for this therapy has to obtain a license as a specialist in endovascular procedures. For neurologists wishing to acquire this license, there are two kinds of training programs: full-time training and concurrent training. Full-time training was chosen by the first author of this review, while concurrent training will be performed by staff in the author's department. The advantage of full-time training is the acquisition of a lot of experience of various diseases that are treated with endovascular procedures and managed in the periprocedural period. However, full-time training has the disadvantages of a requirement to discontinue medical care of neurological diseases except for stroke and employment at a remote institution. The advantages and disadvantages of concurrent training are the reverse of those of full-time training. Neither training system can succeed without cooperation from Departments of Neurology in neighboring universities and the institutional Department of Neurosurgery. It is particularly important for each neurologist to establish a goal of becoming an operator for recanalization therapy alone or for all fields of endovascular procedures because training will differ for attainment of each operator's goal.

In recent years, although the number of elderly patients with breast cancer is increasing, there are very few reports of breast cancer in elderly patients aged 90 years and older. In this study, we examined breast cancer patients who were 90 years of age or older. Patient background characteristics, clinicopathologic features, and treatment strategies were examined for 9 elderly breast cancer patients aged 90 or older who were treated at our department from January 2000 to December 2012. The median age of the patients was 91 (range, 90-99)years, and complications were reported in 7 patients (77.8%). The median tumor diameter was 4.3 (range, 1.4-6.0) cm, and T4 disease was observed in 6 patients (66.7%). Axillary lymph node status was negative in 6 patients (66.7%). Pathological diagnoses were invasive ductal carcinoma in 8 patients and ductal carcinoma in situ in 1 patient. Seven patients were hormone receptor positive and 1 patient was hormone receptor negative. Human epidermal growth factor receptor (HER)-2 status was negative in 8 patients. Surgery was performed safely in 5 patients and there were no signs of postoperative metastases. Four patients were treated with hormone therapy. The response rate( partial response[ PR] and complete response[ CR]) was 50%. Our findings suggest that when treating breast cancer patients aged 90 years or older, it would be necessary to offer medical treatment considering the possibility of comorbidities and the complications associated with medical treatment.

We report the case of a patient with ampullary carcinoma, diagnosed as having liver metastases by staging laparoscopy, who underwent subsequent laparoscopic biliary bypass during the same operation. A 61-year-old man with jaundice was found to have ampullary carcinoma on CT and ERCP. However, no metastatic lesions were detected on FDG-PET, and we decided to perform laparoscopic pancreaticoduodenectomy. After 1 month of bile drainage and control of cholangitis, we performed a preoperative CT scan that indicated the presence of multiple small low-density areas in the liver. However, it was difficult to distinguish whether the hepatic lesions were metastases or inflammatory changes. Therefore, we decided to choose the operative approach based on the findings obtained from staging laparoscopy. During the procedure, small nodules were observed on the liver surface and were resected. As the resected specimens were found to be adenocarcinomas on pathological examination, we performed Roux-en-Y laparoscopic hepaticojejunostomy using running 4-0 PDS sutures. The postoperative course was uneventful and the patient was discharged on postoperative day 18, after the introduction of systemic chemotherapy. Laparoscopic biliary bypass followed by staging laparoscopy is among the useful methods for unresectable peripancreatic malignancies.

A 55-year-old woman presented to our hospital with a chief complaint of abdominal pain. Computed tomography (CT) revealed a massive tumor originating from the tail of the pancreas, with liver and lymph node metastasis. Percutaneous biopsy was performed and yielded a diagnosis of pancreatic neuroendocrine carcinoma. The patient underwent distal pancreatectomy, lateral segmentectomy of the liver, para-aortic lymph node dissection, and cytoreductive surgery for treatment of peritoneal dissemination. Octreotide was administered on post-operative day (POD) 3. Treatment with everolimus (10 mg/day) was initiated on POD 32. Stable disease according to the Response Evaluation Criteria in Solid Tumors( RECIST) was observed for 4 months, and the patient survived for a total of 9 months after surgery. Everolimus was tolerated safely and was effective for the treatment of pancreatic neuroendocrine carcinoma.

An 85-year-old woman with rectal carcinoma was referred to our hospital for surgical treatment. She had a history of constipation treated with oral magnesium oxide. She received 34 g of magnesium citrate (Magcolol P(®)) orally for 2 days as a mechanical bowel preparation prior to the operation. Just before the operation, she suddenly developed nausea, vomiting, and cyanosis and went into cardiac arrest. Despite support by mechanical ventilation, dopamine, dobutamine, and norepinephrine, she exhibited repeated bradycardia that was nearly fatal and required temporary pacing. The following day, her laboratory tests revealed marked hypermagnesemia (14.3 mg/dL). After a hemodialysis session, she recovered dramatically and all vasopressors were withdrawn. We conclude that preoperative mechanical bowel preparation with magnesium-containing cathartics can cause fatal hypermagnesemia in elderly patients even if their renal function is normal.

Objective: In order to identify the factors that influence the swallowing function in patients who develop Wallenberg syndrome (WS) following lateral medullary infarction (LMI), we examined various patient characteristics, including the passage pattern abnormality (PPA) of a bolus through the upper esophageal sphincter (UES)., Methods: Fifty-four pure LMI patients with dysphagia participated in this study. PPA, defined as the failure of bolus passage through the UES corresponding to the intact side of the medulla, was identified during videofluorographic swallowing evaluations of each patient. On brain magnetic resonance imaging, the subjects' lesions were classified vertically into three levels and horizontally into seven levels in relation to the involvement of the ambiguous and/or solitary nuclei. Logistic regression analyses were performed for age, sex, PPA and the vertical and horizontal sites of the lesions., Results: In terms of severity, 15 subjects were categorized as having mild dysphagia, 26 subjects were categorized as having moderate dysphagia and 13 were categorized as having severe dysphagia. Subjects with cephalic lesions, greater vertical spread of the lesion and PPA were more likely to have severe dysphagia. PPA and a greater vertical spread of the lesion were related to the severity of the functional outcome (p<0.01). The horizontal extent of the lesion was not strongly related to the prognosis., Conclusion: The presence of PPA in LMI patients is suggestive of abnormalities in the swallowing pattern and, in turn, damage to the medullary central pattern generator. The presence of PPA and a greater vertical spread of the lesion can be useful predictors of severe dysphagia.

A 74-year-old man presented to a physician with a chief complaint of jaundice. He was diagnosed with bile duct carcinoma and admitted to our hospital. Laboratory data revealed abnormally elevated levels of total bilirubin, serum hepatic transaminase, and CA19-9. Endoscopic retrograde cholangiopancreatography revealed neoplastic stenosis from the hilus hepatis to the common bile duct. Abdominal computed tomography (CT) revealed an enhancing tumor in the hilus hepatis bile duct, and positron emission tomography-CT (PET-CT) revealed abnormal fluorodeoxyglucose accumulation in the tumor. Under a diagnosis of hilar cholangiocarcinoma, the patient underwent an extended right hepatectomy and left hepatico -jejunostomy. Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and CD56. The tumor was diagnosed as primary neuroendocrine carcinoma of the bile duct. The patient exhibited multiple liver metastasis 6 months after the operation. Transcatheter arterial chemoembolization (TACE) was performed for the liver metastasis. Although TACE exerted a cytoreductive effect temporarily, multiple liver abscesses developed. The patient died of liver failure 16 months after the operation. We report this rare case of primary neuroendocrine carcinoma of the bile duct.

A 69-year-old man with recurrent hepatocellular carcinoma (HCC) in S7/8 after radiofrequency ablation therapy (RFA)was admitted to our hospital. Serum alpha-fetoprotein and protein induced by vitamin K absence or antagonists (PIVKA-II) were elevated to 367 ng/mL and 18,973 mAU/mL, respectively. Abdominal computed tomography scan revealed that the size of the tumor was 56 mm and a portal vein tumor thrombus progressed from the right anterior branch to the left main branch(Vp3). The clinical stage was cT3N0M0, cStage III(JPS). He received 3 courses of intra-arterial infusion chemotherapy with cisplatin(CDDP IA-call)into the right hepatic artery at a dose of 65 mg/m2 every 2 months. Elevated serum alpha-fetoprotein(AFP)and PIVKA-II markedly decreased and returned to normal levels after the second course of treatment. The liver tumor and portal vein tumor thrombus disappeared, and only arterioportal shunting remained. The response to treatment was partial response (PR) and complete response (CR), according to the Response Evaluation Criteria In Solid Tumors and the modified version, respectively. He has been alive for more than 1 year without recurrence. CDDP is an effective treatment for advanced HCC with portal vein tumor thrombus.

The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.