Search

This review focuses on cancer, a serious health issue in modern society, and explores the advancements and applications of single-cell RNA sequencing(scRNA-seq)as an advanced technique for understanding its pathobiology. Cancer often arises due to genetic mutations or epigenetic changes, which manifest through fluctuations in gene expression. Therefore, transcriptome information(transcriptomics)plays an indispensable role in cancer research. In this field, there has been a shift from hybridization to next-generation sequencing, and the emergence of scRNA-seq technology enables the analysis of dynamic gene expression properties at the single-cell level. Consequently, significant advancements have been made in cancer research, including understanding complex intercellular variations and interactions, as well as revealing the roles of the tumor microenvironment and immune cells, and the contribution of non-coding RNAs. This review focuses on the progress and applications of scRNA-seq technology, providing an overview of new insights and prospects for cancer research and therapy.

A woman in her 90s underwent laparoscopic hernia repair for a recurrent left inguinal hernia with abdominal wall defect 2 years ago. She came to our department with a complaint of a mass in the hernia wound, which was suspected to be a skin cancer, and the pathology diagnosis was adenocarcinoma. A colonoscopy was performed and she was diagnosed with sigmoid rectal cancer with only skin metastasis and the operation was performed. Laparoscopic anterior resection of the rectum, excision of the skin tumor, mesh removal, and rectus abdominis skin grafting were performed, and these were radical surgery. Simultaneous cutaneous metastasis of rectal cancer is extremely rare, being part of the 2.0% of other sites, and is reported with some literature review.

A 78-year-old man who was diagnosed as having hepatocellular carcinoma(segment 4/8)underwent laparoscopic hepatectomy. About 5 hours after the start of the operation, SpO2 and systolic blood pressure suddenly dropped to 87% and 40 mmHg. EtCO2 level decreased to 8 mmHg and PaCO2 was 48.5 mmHg. Based on the discrepancy between the PaCO2 and EtCO2, the patient was diagnosed as having pneumoperitoneum-induced carbon dioxide embolism. The surgical procedure was immediately interrupted and the patient was hyperventilated with pure oxygen. After surgical interruption, general status was recovered to the normal condition. We carefully restarted the operation and completed it laparoscopically. The patient was discharged from the hospital on the 15th day without any postoperative complications. Carbon dioxide embolization is a serious life-threatening complication that requires careful monitoring.

A woman in her 80s, had undergone radical surgery for an endometrial carcinoma 9 years earlier, and her 5-year postoperative follow-up had been completed without recurrence. She consulted an orthopedic surgeon with a chief complaint of a mass in the left inguinal region, and was referred to surgery after MRI scan revealed lymph node metastases in the left inguinal and external iliac region and a sigmoid colon tumor. Due to postoperative adhesion of the uterine cancer, the colonoscope could not be inserted to the tumor, and no tissue diagnosis was made. CT and PET scans revealed a sigmoid colon tumor plus periungual lymph node metastasis, and it was determined that radical surgery was possible, and the patient underwent resection. Surgery was performed by laparoscopic resection of the sigmoid colon and lymphadenectomy, with R0 resection. The sigmoid colon tumor and lymph nodes were of the same histology as the 9-year-old endometrial carcinoma, leading to the diagnosis of colon and lymph node recurrence 9 years after endometrial carcinoma surgery.

A 64-year-old woman underwent right hemicolectomy for transverse colon cancer. Histopathological findings revealed T, type 2, 24×22 mm, tub2, pT2N1a(1/23)M0, and pStage Ⅲa. Postoperative adjuvant chemotherapy was not administered at the patient's request. One year after surgery, carcinoembryonic antigen(CEA)level was elevated, and Gd-EOB-DTPA- enhanced MRI revealed a nodule in segment 2 and 4/8 of the liver. Based on the diagnosis of hepatic metastasis, laparoscopic partial hepatectomy was performed. Three years after hepatectomy, CEA level was found to be elevated again, and chest CT showed a solitary pulmonary nodule in segment 7 of the right lung. With a diagnosis as pulmonary metastasis, FOLFIRI plus bevacizumab was performed. After 41 courses of FOLFIRI plus bevacizumab, the pulmonary nodule decreased in size, and no new lesions appeared. The chemotherapy was terminated at the patient's request. Six months later, the pulmonary nodule increased in size, and thoracoscopic partial pulmonary resection was performed. Hepatic and pulmonary resection specimens were histopathologically consistent as metastasis of colorectal cancer. The patient has been alive without recurrence for about 4 years after final surgery(pulmonary resection)without postoperative adjuvant chemotherapy. We report a case of long-term survival with metachronous hepatic and pulmonary metastases from transverse colon cancer by multidisciplinary treatment.

A 67-year-old woman presented with a history of upper abdominal pain and weight loss. Physical examination revealed a lump in the right lower quadrant. She had undergone esophagogastroduodenoscopy at another hospital ten years ago, which showed a 15-mm elevated lesion in the duodenal bulb. The patient had not undergone further examinations or received treatment during the 10 years. Esophagogastroduodenoscopy conducted in our hospital revealed an enlarged tumor that was difficult to assess on the whole image. The tumor was diagnosed as a well-differentiated adenocarcinoma based on a biopsy specimen. Enhanced computed tomography revealed a hypervascular duodenal tumor with liver and lymph node metastases. The patient was treated with capecitabine plus oxaliplatin for the duodenal cancer. Lymph node metastases increased markedly after 2 courses of chemotherapy. The patient died 3 months after the initiation of chemotherapy. The natural history of sporadic non-ampullary duodenal epithelial tumors remains to be fully elucidated due to the low incidence rate. This case suggests that sporadic non-ampullary duodenal epithelial tumors have a biological potential for invasive malignancy.

Our patient was a man in his 70s who underwent proximal gastrectomy with double tract reconstruction in 2013. He was diagnosed with cStage Ⅳ unresectable remnant gastric cancer with paraaortic lymph node metastases in 2021. He was treated with 5 courses of S-1 plus oxaliplatin therapy. Computed tomography revealed that the lymph node metastases had decreased in size after treatment. We performed conversion surgery and achieved R0 resection. Furthermore, the elevated jejunum was preserved and total gastrectomy was possible without re-anastomosis. Postoperative adjuvant chemotherapy with S-1 was started and he remains alive without recurrence at 6 months postoperative.

The patient was 40s male, who underwent laparoscopic low anterior resection for his upper rectal cancer with final pathology results of tub2, pT3(SS), no lymph metastasis and fStage Ⅱ. He was followed up without adjuvant chemotherapy. Half a year after surgery, tumor marker was elevated and CT scan revealed multiple liver metastases. He was treated with oxaliplatin, irinotecan, Leucovorin and 5-fluorouracil(FOLFOXIRI)plus bevacizumab because of RAS mutant type. In the third courses, he has pain in the lower extremities and was diagnosed with acute lower extremity arterial occlusion. Subsequently, chemotherapy was resumed with the exception of bevacizumab, in combination with DOAC, which resulted in tumor shrinkage and allowed resection of the liver metastases.

In general, nitrite in food is extracted under slightly alkaline conditions, deproteinized, and analyzed by a colorimetric method using color development by diazotization. However, depending on the sample, the sample solution may become cloudy and difficult to filter by the deproteinization treatment of the analytical method. Recently, an improved analytical method that solves these problems has been reported. Therefore, a validation study was performed on the improved analytical method was performed. The concentrations of sodium nitrite added to cod roe, fish sausage, and ham, which were not labeled with sodium nitrite, were set at the upper limits of the standards for use. We set the target values of 70-120% for trueness, less than 15% for intralaboratory reproducibility, and less than intralaboratory reproducibility for repeatability. As a result, the target values were met for the three samples verified: 88-92% for trueness, 2.0-3.0% for repeatability, and 3.2-4.3% for intralaboratory reproducibility. In addition, an interlaboratory study was conducted by eight institutes on the improved analytical method for nitrite. At each institution, sodium nitrite was added to the same three samples as in the validation study, at concentrations equivalent to twice the lower limit of quantification and the upper limit of the standards for use and analyzed in triplicate. The estimated trueness from the obtained analyses ranged from 82 to 95%, the repeatability ranged from 2.3 to 5.8%, and the inter-room reproducibility ranged from 3.5 to 11%. Thus, the improved analytical method could be useful for determining nitrite in foods.

Case 1 is a 56-year-old man. During postoperative adjuvant chemotherapy for pancreatic cancer, weakness in the right upper and lower limbs appeared, and a head CT scan was performed, but no abnormal findings were noted. Diffusion- weighted MRI scan of the head showed multiple cerebral infarcts, and a diagnosis of Trousseau syndrome was made. Case 2 is an 86-year-old man. During chemotherapy for postoperative recurrence of distal bile duct carcinoma, he developed weakness in the right upper and lower limbs, and a head MRI scan was performed. Diffusion-weighted MRI showed scattered high-signal areas, and a diagnosis of Trousseau syndrome was made. Trousseau syndrome is a condition in which stroke is caused by hypercoagulability associated with malignant tumor. The initial symptoms of cerebral infarction in patients with cancer are similar to those of chemotherapy-induced adverse events and brain metastases, and therefore, a head MRI scan is recommended even if there is no obvious abnormality on head CT scan.

A 33-year-old man was admitted due to dyschezia and melena. Colonoscopy revealed a circulating type 4 rectal tumor. Further examination revealed intestinal obstruction due to rectal cancer, paraaortic lymph node metastasis, and multiple bone metastases, and an ileus tube was transanally inserted for decompression. Bone scintigraphy revealed multiple abnormal uptake regions in the entire skeleton. We planned to perform primary tumor resection and postoperative adjuvant chemotherapy and radiotherapy administration. Peritoneal signs in the lower abdomen appeared after 6 days of tube insertion. Abdominal computed tomography demonstrated intestinal perforation, and emergency surgery was performed. During the surgery, tube penetration in the anterior abdominal wall was observed in the sigmoid colon proximal to the tumor. Postoperatively, the patient developed disseminated intravascular coagulation(DIC). The patient had multiple bone metastases and juvenile cells in peripheral blood figure analysis; therefore, we concluded that DIC was caused by carcinomatosis of the bone marrow. After an informed consent was obtained, FOLFOX4 with simultaneous DIC treatment was initiated, and DIC remission was observed. The patient was transferred to a different hospital near his home, but died 35 days postoperatively.

The patient was a 74 year-old woman. She came to the hospital with the chief complaint of vomiting, difficulty walking, and disorientation. The MRI study showed increased FLAIR and DWI signals in the bilateral medial thalamus. Abdominal enhanced CT scan showed a 2.4 cm tumor in the jejunum. And ileus due to small intestinal tumor was observed. She diagnosed Wernicke's encephalopathy associated with gastrointestinal transit disorder. Vitamin B1 300 mg/day for 3 days was started, and eye movements and disorientation improved on the day following the start of administration. On the 10th day after admission, partial resection of the small intestine was performed for a small intestinal tumor. She was diagnosed as small intestinal cancer. She was transferred to the hospital on the 20th postoperative day.

Objectives: This study aimed to examine the present state of activities of occupational health physicians (OHPs) and companies' opinions about them., Methods: Questionnaires, to be answered anonymously, were sent to 1,898 companies with ≥ 50 employees. We analyzed the data according to type of industry and the size of the company., Results: We received 692 responses. First, we compared the data with the results of a previous study we had conducted in 2003. The percentage of companies that employed OHPs was found to have increased from 77% to 97%. The implementation rate of work place inspection conducted by OHPs had increased from 41% to 65%, and the attendance rate of health committees increased from 24% to 56%. Regarding overtime, we found that the percentage of workers who did more than 80 hours of overtime work per month had decreased from 29% to 7%, but in the transportation industry the high rate of 38% was maintained. Stress assessments were conducted by 98% of the companies with ≥ 50 employees., Conclusions: This study determined the present situation in companies, with regard to recent law revisions. Stress assessments are carried out more frequently, the number of workers doing overtime has decreased, and measures against second-hand smoke are being promoted. In addition, we found an increase in the frequency of work place inspection and attendance of health committees, but in one-third of the companies these were not carried out.

Aim: The present study investigated the relationship between the type of residential area and each factor of the International Classification of Functioning, Disability and Health (ICF) framework among elderly subjects receiving home-visit rehabilitation., Methods: This was a cross-sectional study conducted at two institutions. A total 84 participants (46 men and 38 women, age: 79.1±7.8 years old) who were receiving home-visit rehabilitation in urban and rural areas were examined. The parameters measured included the modified Gait Efficacy Scale (mGES), grip strength, 30-seconds chair stand test (CS-30), Functional Independence Measure (FIM), Life-Space Assessment (LSA), Frenchay Activities Index (FAI), Ikigai-9, and Home and Community Environment (HACE), which is based on the ICF concepts of health status, physical structure, physical and mental functions, activities, participation, personal factors, and environmental factors respectively; these points were evaluated by physical or occupational therapists. The health status was based on the diagnosis obtained from the clinical record., Results: Receiving home-visit rehabilitation in a rural area was significantly associated with the LSA (odds ratio [OR]=1.075, p=0.028), optimistic and positive feelings for life (OR=0.698, p=0.040), and community mobility scores (OR=5.755, p=0.001)., Conclusions: Environmental factors, activities, and personal factors differed depending on the region where the elderly subject received home-visit rehabilitation. Thus, intervention methods concerning home-visit rehabilitation may need to be adjusted according to the region where the patient lives.

A 59-year-old woman presented with a left adrenal tumor 4 cm in diameter. The ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy showed apparent accumulation in the left adrenal tumor. However, the patient had no sign or symptoms suggesting pheochromocytoma. No biochemical evidence of catecholamine excess was noticed. Computed tomography (CT) revealed relatively strong enhancement in the arterial phase, which persisted until the portal phase. The computed tomography (CT) and magnetic resonance imaging showed 2 liver nodule suspected to be metastatic tumors. No ¹²³I-MIBG accumulation was seen in these nodules. CT also showed thyroid nodules with calcification, which suggested papillary thyroid cancer. Based on the findings, open left adrenalectomy, partial hepatectomy and segmentectomy were performed under the clinical diagnosis of pheochromocytoma and metastatic liver tumors. Histopathological diagnosis was adrenocortical cancer. There was only lymphocyte infiltration in the liver nodules. Postoperative recovery was uneventful, and the patient underwent partial thyroidectomy 6 months later. The pathological diagnosis was papillary thyroid cancer. She has been without recurrence or metastases for 18 months after adrenalectomy. We found only 6 cases of MIBG scintigraphy-positive adrenocortical cancer in the literature. The mechanisms for MIBG uptake in adrenocortical cancer are discussed with a review of the literature.

In very elderly patients with low back pain, we must consider the possibility of osteoporotic vertebral fracture (OVF). In most patients with OVF, improvement can be observed without surgical intervention. However, even after providing the best possible conservative treatment, symptom recovery is not observed in some patients, and such patients experience delayed neurological deficits due to neural compression with the proceeding deformity of the vertebral body. Moreover, it is well known that once patients have OVF, the risk of another osteoporotic fracture in them increases. The clinical course of such patients eventually results in the loss of healthy life and increased mortality. Therefore, we should initiate medical treatment for osteoporosis at the earliest possible when OVF is detected in a patient. Patients who remain symptomatic even after undergoing adequate conservative therapy are candidates for balloon kyphoplasty. However, this minimally invasive surgery has some pitfalls. Furthermore, occasionally, we have to select instrumentation surgery for patients with delayed neurological deficits. In this "super-aged society," neurosurgeons also encounter patients with OVF not only in surgical situations but also in outpatient clinics. Thus, we should be aware about the clinical options for the management of osteoporosis.

Lumbar canal stenosis is the most common pathological condition causing spinal degeneration. Symptomatic patients who fail conservative treatment are considered candidates for surgical treatment. Many types of minimally invasive procedures for lumbar decompression have been proposed, most of which are effective and have shown good long-term results. However, in special cases, a second operation may be needed for spondylolisthesis caused by degeneration of the same segment. Two major minimally invasive approaches are available for bilateral decompression of lumbar canal stenosis: unilateral approach and midline approach. The unilateral approach is used to preserve midline structures, the contralateral facet joint, and the contralateral paravertebral muscle. The midline approach is used to preserve the left and right facet joints and the enthesis of the paravertebral muscle. These two approaches are suitable for specific situations based on their own concepts. Nevertheless, it is important to understand the advantages and disadvantages of each procedure. In this article, the varieties of lumbar decompressive methods and the pitfalls of decompression procedures will be discussed.

Objectives: Optimal beam quality for detection of pulmonary nodules in digital chest radiography using CsI-flat panel detector (FPD) was investigated in consideration of image quality and patient dose., Methods: The human chest phantom with inserted imitated nodules (diameter: 10 mm, CT value: +30 Hounsfield unit (HU), -375 HU, -620 HU) was used for the measurement of contrast-to-noise ratio (CNR) of imitated nodules by twenty beams arranged by five tube voltages and four filters., Results: The CNR varies with X-ray tube voltage and added filter. CNR correlates weakly to the tube voltage, fairly to the effective energy in second-order polynomial and strongly to the quality index (effective energy divided X-ray tube voltage). In order to improve the CNR, the effective energy and the quality index are kept about 50 keV and more than 0.5, respectively, using an 80-100 kV beam with a copper filter., Conclusion: A 90 kV (2.5 mm Al inherent filtration) beam with a 0.15 mm copper filter and a 90 kV or 100 kV (2.5 mm Al inherent filtration) beam with a 0.2 mm copper filter are appropriate for chest radiography using CsI-FPD.

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, and AXL, among others. This drug is considered to exert excellent antitumor effects by inhibiting these targets simultaneously. Significant improvement in the primary endpoint (overall survival or PFS) were observed in patients on CAB in comparison with controls in a phase-III study in patients with renal cell carcinoma, progressed after treatment with anti-angiogenic agents, and in another phase-III study in patients with previously treated, advanced hepatocellular carcinoma. These results led to the approval of CAB in Japan in 2020 as a therapeutic agent for unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma progressed after cancer chemotherapy, under the trade name of CABOMETYX ® (20 mg, and 60 mg tablets). It has been suggested that CAB may modulate the immune system in favor of antitumor immunity and combined use with PD-1 checkpoint inhibitors may exert a synergistic effect. In a phase-III study that examined the efficacy of combination therapy with CAB and nivolumab in treatment-naive patients with advanced renal cell carcinoma, progression-free survival was significantly increased in patients on combination therapy over patients on sunitinib monotherapy. Three global phase-III clinical studies of combination therapy with atezolizumab and CAB in patients with non-small cell lung cancer, castration-resistant prostate cancer, and renal cell carcinoma, are in progress to confirm the efficacy of CAB.

Objectives: Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan., Methods: Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion., Results: Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12)., Discussion: CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.

Ependymoma is the most common primary intramedullary tumor of the spinal cord, accounting for a quarter of these tumors. We experienced a case of 'ependymoma of the spinal cord with a cystic lesion that presented as an intradural extramedullary tumor extending from the thoracic to lumbar vertebrae. In review of past literature on reports of spinal intradural extramedullary ependymoma, lesions spanning three or more vertebrae with cystic lesions were frequent, and about half were World Health Organization grade II or higher. Dissemination or recurrence of these tumors may occur after surgery. There is no consensus on postoperative adjuvant therapy for intradural extramedullary spinal ependymoma, but careful consideration should be given to the intraoperative findings and the characteristics of the tumor.

Purpose: Automated analysis of skeletal muscle in whole-body computed tomography (CT) images uses bone information, but bone segmentation including the epiphysis is not achieved. The purpose of this research was the semantic segmentation of eight regions of upper and lower limb bones including the epiphysis in whole-body CT images. Our targets were left and right upper arms, forearms, thighs, and lower legs., Method: We connected two 3D U-Nets in cascade for segmentation of eight upper and lower limb bones in whole-body CT images. The first 3D U-Net was used for skeleton segmentation in whole-body CT images, and the second 3D U-Net was used for eight upper and lower limb bones' segmentation in skeleton segmentation results. Thirty cases of whole-body CT images were used in the experiment, and the segmentation results were evaluated using Dice coefficient with 3-fold cross-validation., Result: The mean Dice coefficient was 93% in the left and right upper arms, 89% in the left and right forearms, 95% in the left and right thighs, and 94% in the left and right lower legs., Conclusion: Although the accuracy of the segmentation results of relatively small bones remains a challenge, the semantic segmentation of eight regions of upper and lower limb bones including the epiphysis in whole-body CT images has been achieved.

A 56-year-old man presented with a painless swelling of the left scrotum. Cytologic examination of blood stained hydrocele fluid suggested malignancy. Left high orchiectomy was performed under the suspicion of malignant tumor of the tunica vaginalis testis. The final pathologic report revealed malignant mesothelioma of the tunica vaginalis testis. There is no evidence of recurrence after 114 months followup. It is important to perform en bloc resection for this disease to prevent recurrence.

Zinc (Zn) is one of the essential trace elements required for human developments and it plays an important role in the maintenance of numerous tissue homeostasis. The amount of Zn levels was below the constant level which induced the various harmful health effects such as impaired growth, hair loss, taste disturbance, anorexia. Maintenance of Zn homeostasis in body mainly depends on two families of Zn transporters; Zrt- and Irt-like proteins (ZIPs), and Zinc transporters (ZnTs). Some studies based on the gene knock-out mice and human genetic analysis have been reported the relationship between zinc transporters and human diseases. Recent studies have shown that Zn transporter-mediated Zn ion behaves as a signaling factor, called Zn signal, that exerts a multiple function in cellular events. In this review article we describe important physiological roles of Zn transporters and their contribution at the molecular, biochemical, and genetic levels underlying the mechanisms of human diseases.

As a primate animal model for neuroscience research, the common marmoset (Callithrix jacchus) provides an unprecedented opportunity to gain a better understanding of the human brain function and pathophysiology of neurological and psychiatric disorders, thereby helping in the diagnosis and treatment of those disorders. The marmoset is particularly useful in studying the neural mechanisms underlying social behavior, as their prosocial behavior and visual and vocal communication systems are well-developed. Despite recent advances in biotechnology such as the creation of genetically engineered marmosets, our understanding of the marmoset brain, including its dysfunction in disease, at the circuit level remains limited due to the lack of comprehensive knowledge of the neuronal connections in the marmoset brain. Here we describe the development of genetic and viral engineering techniques for a particular type of neuron in non-transgenic animals. These approaches, combined with rabies viral tracing, imaging, and electrophysiology, will make it possible to map the connectome and relate neuronal connectivity to function in the marmoset brain. Such circuit-level studies will open a new avenue for non-human primate research that can bridge the gap between basic research and human studies.

A 30-year-old woman who was 14 weeks pregnant was admitted to our hospital due to purpura, nasal bleeding, and abdominal pain. She was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP) based on the presence of hemolytic anemia, thrombocytopenia, decreased ADAMTS 13 activity (<0.01 IU/ml), and high ADAMTS 13 inhibitor levels (4.8 BU/ml). Plasma exchange (PE) and steroid therapy were immediately administered. However, because she did not respond to these therapeutic approaches, rituximab was additionally administered on the sixth day of treatment. The level of ADAMTS 13 inhibitor increased to 12.5 BU/ml on the seventh day. Renal insufficiency, disturbed consciousness, and genital bleeding did not improve in spite of daily PE, steroid therapy, and second dose of rituximab. She finally died after sudden convulsions on the 14th day. Although the treatment outcomes of TTP have remarkably improved, some cases are refractory to therapy. Establishment of adequate treatment strategies for acquired TTP in pregnant women is required.

Traumatic carotid cavernous fistula(CCF)is known to present a direct connection between the cavernous segment of the internal carotid artery(ICA)and the cavernous sinus(CS). In rare cases, the fistula is formed between the intradural internal carotid artery(ICA)and the cavernous sinus(CS)via a pseudoaneurysm(pAN), requiring appropriate management and aggressive surgical treatment. We describe a 58-year-old man who sustained a severe head injury diagnosed as traumatic CCF treated with an intradural pAN procedure and transarterial coil embolization combined with a Low-profile Visualized Intraluminal Support(LVIS)stent. While slow arteriovenous shunt flow persisted at the end of the surgery, the fistula was completely occluded on the digital subtraction angiography obtained 2 weeks after the procedure. It was suspected that the flow-diversion effect of the LVIS stent might have caused the curable progression of the fistula occlusion.

Background and Purpose: Gastrointestinal bleeding is an important complication in the acute phase of hemorrhagic stroke. In this study, we aimed to identify the risk factors for gastrointestinal bleeding in patients with hemorrhagic stroke despite the administration of antiulcer drugs., Methods: We conducted a retrospective cohort study of our hemorrhagic stroke cases. We analyzed the background factors associated with gastrointestinal bleeding in the study population and their outcomes., Results: The study included 837 patients: 598 with intracerebral hemorrhages and 239 with subarachnoid hemorrhages. Among them, 22 patients developed gastrointestinal bleeding. Intraventricular hemorrhage (P=0.0019) and ongoing oral anticoagulant use (P=0.0177) were significantly associated with gastrointestinal bleeding. Gastrointestinal bleeding was significantly associated with severe disability at discharge (P=0.0333) and number of days of hospitalization (P=0.0190)., Conclusions: The risk factors of poorly controlled gastrointestinal bleeding during the acute phase of hemorrhagic strokes were intraventricular hemorrhage and use of anticoagulant drugs. Patients with a high risk for gastrointestinal bleeding need to be identified and to be given effective prophylactic therapy. (Received October 12, 2017; Accepted March 29, 2018; Published August 1, 2018).

Ixazomib (Ninlaro ® capsule) is an oral small molecule 20S proteasome inhibitor created by Millennium Pharmaceuticals, Inc (Takeda Oncology Company). Ubiquitin proteasome system is a major regulatory system for maintaining protein homeostasis, and an important mechanism for degrading proteins, such as those involved in proliferation regulation, cell cycle regulation and apoptosis, in cells. Ixazomib selectively and reversibly binds to the β5 subunit of the 20S proteasome, inhibits its chymotrypsin-like activity, and thereby accumulates ubiquitinated proteins. It induces ER stress and apoptosis of myeloma cells. The phase 3, randomized, double-blind, multicenter global study (TOURMALINE-MM1) in patients with relapsed and/or refractory multiple myeloma, who have received 1 to 3 prior lines of therapy, showed that addition of ixazomib to lenalidomide-dexamethasone (ixazomib-Rd) demonstrated significant improvement in progression-free survival (hazard ratio = 0.742, P = 0.012) versus placebo-Rd (20.6 vs. 14.7 months in the median) (data cut-off as of October 30, 2014). Ixazomib has been approved by the United States Food and Drug Administration in November 2015, and the European Medicines Agency in November 2016 for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy. In Japan, ixazomib was approved for the treatment of relapsed and/or refractory MM in March, 2017. It is expected to demonstrate that the oral proteasome inhibitor ixazomib is an effective and convenient treatment option in clinical practice.

To investigate the efficacy and safety of first-line Pazopanib advanced or metastatic renal cell carcinoma (RCC): a single-institution study. (Patients and methods) We gathered 23 RCC patients treated between April 2014 and February 2018 in our institution and examined the treatments outcome and adverse events (AEs). (Results) Their risk criteria were categorized as follows: Favorable (n=2), Intermediate (n=12) and Poor (n=9) by International mRCC Database Consortion (IMDC). Median progression free survival (PFS) was 8.6 months and median overall survival (OS) was unreached. Best response (BR) of Pazopanib was partial response (PR): n=10, 50.0%, stable disease (SD): n=8, 40.0% and progression disease (PD): n=2, 10.0% (Three patients had no evaluable data,). AEs of Grade3 had liver dysfunction (n=3), thrombocytopenia (n=2), hand-foot syndrome (n=1), vomiting (n=1) and bowel bleeding (n=1). (Conclusion) The fist-line pazopanib demonstrated good clinical benefit with well-tolerance.

In June 1997, the patient underwent an operation for cecal colon cancer pStage II .I n May 1999, a liver metastasis at S6 was detected and the patient received a partial liver resection.In April 2004, a liver metastasis in S4 was detected and another partial liver resection was performed.In November 2008, he complained of hemoptysis and cough.The chest CT examination showed lymph node metastases in the mediastinum that invaded the left main bronchus.We performed chemo-radiotherapy for local control from January 2009. Because the lymph nodes were reduced remarkably and clinical complaints disappeared, we administrated a mFOLFOX6 regimen from June.We recognized the effect of treatment to be a complete response.In February 2014, we detected a lymph nodes recurrence around a right pulmonary artery.We performed chemo-radiotherapy again because the patient declined surgery.However, lymph node metastases did not completely respond.We then performed chemotherapy 30 times using a FOLFIRI plus panitumumab regimen.On PET-CT, the recurrent lesion did not show a hot spot.We experienced a case that responded to chemo-radiotherapy for long-term control of lymph node recurrence.

A 69-year-old woman was referred to our department for refractory cystitis. Incomplete emptying of the bladder was observed, and symptoms did not improve after medication. Clean intermittent catheterization was initiated. Two years after introduction of catheterization, a mass in the bladder dome was detected by routine abdominal ultrasonography. She was diagnosed with malignant tumor of the bladder diverticulum based on cystoscopy, computed tomography, and magnetic resonance imaging. Partial cystectomy and lymph node dissection was performed following transurethral resection of the bladder tumor. Histopathology revealed squamous cell carcinoma and no signs of lymph node metastasis. She is alive and recurrence-free 28 months after surgery.

Half scan can acquire images at the 200° rotation in image-guided radiation treatment using cone-beam CT and is useful to evaluate the influence of the half-scan-imaging start angle and imaging direction on image registration accuracy. The half-scan-imaging start angle is changed from 180° to 340° in the clockwise direction and from 180° to 20° in the counter clockwise direction to calculate the registration error. As a result, registration errors between -0.37 mm and 0.27 mm in the left and right directions occur because of the difference in the imaging start angle and approximately 0.3° in the gantry rotation direction because of the difference in the imaging direction. Because half scan does not have data for 360° rotation, depending on the subject structure, inconsistency of opposing data can lower reconstruction accuracy and cause a verification error. In addition, in image acquisition during rotation, the slower the shutter speed is, the more the actual gantry angle and angle information of the image are apart, which is considered the cause of rotation errors. Although these errors are very minute, it is thought that there is no influence on the treatment effect, but these errors are considered an evaluation item indispensable for ensuring the accuracy of high-precision radiation treatment. In addition, these errors need to be considered for ensuring the quality of high-precision radiation treatment.

Although penetrating head injuries are very rare in Japan, an extremely rare case is reported in which an ivory chip, embedded in the subcutaneous tissue by a cosmetic rhinoplasty, penetrated the cranium. A 69-year-old woman with a psychiatric disorder suddenly jumped down from a window and bruised her face. The ivory chip went into her left frontal lobe via the frontal sinus. At surgery, it was completely removed via the nasion. There were no postoperative complications after adequate frontal sinus repair and closure of dura mater with a piece of pericranium. The literature dealing with Japanese penetrating head injuries was also reviewed. (Received May 27, 2015; Accepted December 1, 2015; Published June 1, 2016).

We analyzed 11 patients with multiple myeloma (MM) treated using denosumab in our institute. The median age was 69 years (range, 54-76 years), and 7 patients were male. Seven patients had presented with newly diagnosed MM. Four patients were initially treated with zoledronic acid, which was then later switched to denosumab. The median number of injections was 15 (range, 1-27). No patients developed skeletal-related events (SRE) during denosumab treatment. Hypocalcemia was defined as serum calcium levels below the baseline in all patients. To prevent hypocalcemia, 8 patients were administered oral calcium. The first course of denosumab injections in 9 patients resulted in more marked decreases in serum calcium concentrations than subsequent courses. Two patients discontinued denosumab after osteonecrosis of the jaw (ONJ) was suspected, but squamous cell carcinoma was later identified in one of these cases. Denosumab might be effective and safe for preventing SRE. Cautionary measurement of serum calcium concentrations and prophylactic supplementation with oral calcium are warranted to avoid hypocalcemia after the first denosumab injection. The possibility of ONJ also merits attention. The clinical diagnosis of ONJ should be considered based on performing appropriate histological analyses.

The risk of anticoagulant-associated intracranial hemorrhage(ICH)is relatively low in patients treated with non-vitamin K antagonist oral anticoagulants(NOAC). The anticoagulant-associated ICH comprises mainly intraparenchimal hemorrhage. Subdural hematoma and subarachnoid hemorrhage(SAH)are rare complications after treatment with NOAC, trauma being the most common cause for these two types of ICH. We report a case of non-traumatic convexal SAH(cSAH)associated with Apixavan. A 68-year-old man with repeated history of cerebral embolism with cardiogenic cause presented with weakness of the lower limbs. Magnetic resonance imaging revealed infarctions, and treatment with apixaban(5 mg twice per day)was administered. Three days later, SAH in the right superior frontal sulcus was discovered incidentally on computed tomography(CT). NOAC-associated SAH is a rare manifestation. Cerebral amyloid angiopathy(CAA)is the most common cause of cSAH in the elderly, and cSAH is supposed to be a warning sign of cerebral hemorrhage in CAA. Patients with CAA started on NOAC require careful monitoring.

Minimally invasive esophagectomy has become popular as a surgical procedure for esophageal cancer. We describe bilateral continuous thoracic paravertebral blocks for perioperative pain management in 3 patients who underwent minimally invasive esophagectomy. After anesthesia induction, bilateral thoracic paravertebral catheters were placed under ultrasound guidance with the patients in left lateral decubitus position at the sixth or seventh right intercostal space and eighth or ninth left intercostal space, respectively. Multiple ports for thoracoscopic procedures were located between the right third and ninth intercostal spaces. Laparoscopy-assisted gastric tube reconstruction was performed with skin incisions at bilateral T7-10 dermatomes. Intraoperative intermittent bolus injections of ropivacaine through the thoracic paravertebral catheters were used in combination with sevoflurane-remifentanil anesthesia, followed by continuous thoracic paravertebral infusion of ropivacaine for postoperative analgesia with continuous intravenous fentanyl infusion and periodical intravenous acetaminophen administration. Numerical rating scales of postoperative pain at rest and when coughing were 4 or less for 48 hr after surgery. No complications related to thoracic paravertebral catheterization were observed. Bilateral continuous thoracic paravertebral blocks at different intercostal levels can provide good perioperative analgesia for minimally invasive esophagectomy.

When crises such as natural disasters or industrial accidents occur in workplaces, not only the workers who are injured, but also those who engage in emergency or recovery work may be exposed to various health hazards. We developed a manual to enable occupational health (OH) experts to prevent health hazards. The manual includes detailed explanations of the characteristics and necessary actions for each need in the list of "OH Needs During Crisis Management" developed after an analysis of eight cases in our previous research. We changed the endings of explanatory sentences so that users could learn how often each need occurred in these eight cases. We evaluated the validity of the manual using two processes: 1) Providing the manual to OH physicians during an industrial accident; 2) Asking crisis management experts to review the manual. We made improvements based on their feedback and completed the manual. The manual includes explanations about 99 OH needs, and users can learn how and what to do for each need during various crisis cases. Because additional OH needs may occur in other crises, it is necessary to collect information about new cases and to improve the comprehensiveness of the manual continuously. It is critical that this crisis management manual be available when a crisis occurs. We need to inform potential users of the manual through various media, as well as by posting it on our website.

Peritoneal dissemination (PD) is the most common type of metastasis in advanced gastric cancer. The standard treatment of gastric cancer patients with PD is combination therapy with S-1 and cisplatin (SP therapy). Here, we describe the results of SP therapy for gastric cancer with PD. Sixteen gastric cancer patients with PD were treated with SP therapy as first-line chemotherapy. Second-look staging laparoscopy was performed for 10 patients who showed a good response to SP therapy. Gastrectomy was performed for 5 patients with P0CY0 and 1 case with P0CY1. The median survival time of all 16 patients was 571 days (19 months). The patients, who had surgery, had a significantly better survival time than the others (25 months vs 12.7 months). In conclusion, SP therapy is effective for gastric cancer with PD, and surgery for cases showing a good response to chemotherapy might improve the prognosis of patients with PD.

We created a new normal database of elderly individuals (Tsukuba-NDB) for easy Z-score Imaging System (eZIS), a statistical imaging analysis software, comprised of 44 healthy individuals aged 75 to 89 years. The Tsukuba-NDB was compared with a conventional NDB (Musashi-NDB) using Statistical Parametric Mapping (SPM8), eZIS analysis, mean images, standard deviation (SD) images, SD values, specific volume of interest analysis (SVA). Furthermore, the association of the mean cerebral blood flow (mCBF) with various clinical indicators was statistically analyzed. A group comparison using SPM8 indicated that the t-value of the Tsukuba-NDB was lower in the frontoparietal region but tended to be higher in the bilateral temporal lobes and the base of the brain than that of the Musashi-NDB. The results of eZIS analysis by Musashi-NDB in 48 subjects indicated the presence of mild decreases in cerebral blood flow in the bilateral frontoparietal lobes of 9 subjects, precuneus and posterior cingulate gyrus of 5 subjects, lingual gyrus of 4 subjects, and near the left frontal gyrus, temporal lobe, superior temporal gyrus, and lenticular nucleus of 12 subjects. The mean images showed that there were no visual differences between both NDBs. The SD images intensities and SD values were lower in Tsukuba-NDB. Clinical case comparison and visual evaluation demonstrated that the sites of decrease in blood flow were more clearly indicated by the Tsukuba-NDB. Furthermore, mCBF was 40.87 ± 0.52 ml/100 g/min (mean ± SE), and tended to decrease with age. The tendency was stronger in male subjects than female subjects. Among various clinical indicators, the platelet count was statistically significantly correlated with CBF. In conclusion, our results suggest that Tsukuba-NDB, which is incorporated into a statistical imaging analysis software, eZIS, is sensitive to changes in cerebral blood flow caused by Cranial nerve disease, dementia and cerebrovascular accidents, and can provide precise diagnosis of these brain diseases in the rapidly aging Japanese population.