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Background: Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment., Patients and Methods: One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters., Results: ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02-7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82-11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01-10.17), p = 0.049] as independent predictors of ER., Conclusions: For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery., (© 2021. The Author(s).)

The patient was a 57-year-old male. He was diagnosed with locally advanced rectal cancer infiltrating the left levator ani muscle. Chemotherapy(S-1 plus L-OHP plus bevacizumab regimen)was started for the purpose of obtaining a negative circumferential radial margin. After the second course, he presented with perforation of the sigmoid colon for which an emergency operation was performed. The perforation was located 5 centimeters above the tumor in the sigmoid colon. We performed partial resection of the sigmoid colon to repair the perforation and create a sigmoid colostomy. CT, after the initial S-1 plus L-OHP plus bevacizumab chemotherapy regimen, revealed tumor shrinkage. Following 2 more courses of chemotherapy( S-1 plus L-OHP regimen), we performed transanal total mesenteric excision(taTME)as curative surgery. R0 resection was achieved. The combined transanal and laparoscopic approach was highly effective for a patient with pan-peritonitis.

Background: We discuss the significance of neoadjuvant chemotherapy for resectable simultaneous liver metastases in our department., Subject: We examined 73 cases of resectable simultaneous colorectal liver metastases surgeries occurred in our department from 2000 to 2019., Results: There were 13 patients in the chemotherapy before colorectomy group(before colorectomy group), 24 patients in the chemotherapy before hepatectomy group(before hepatectomy group), and 36 patients in the no chemotherapy group(no chemo group). Five-year overall survival in Grade A/B was 77.8%/100% in the before colorectomy group, 50.0%/42.4% in the before hepatectomy group and 45.6%/66.2% in the no chemo group. Three-year progression-free survival in Grade A/B was 51.9%/50.0% in the before colorectomy group, 16.7%/40.4% in the before hepatectomy group and 46.5%/55.6% in the no chemo group. Six patients in the before colorectomy group had no local recurrence, lymph node recurrence, or peritoneal dissemination., Conclusion: Patients in the before colorectomy group were expected to have prolonged survival. There was no local recurrence, lymph node recurrence, or peritoneal dissemination in the before colorectomy group, suggesting the possibility of controlling them.

Objective: We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients., Methods: Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT., Results: In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015-3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071)., Conclusions: This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

We report a case of unresectable gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases leading to conversion therapy. A 70s-year-old man visited previous doctor with epigastralgia. He was diagnosed as stage Ⅳ gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases by upper gastrointestinal endoscopy, contrast enhanced computer tomography(CT), and positron emission tomography(PET). After a regimen consisting of 6 courses of capecitabine plus cisplatin plus trastuzumab, para-aortic lymph node metastasis and liver, lung, and bone metastases were absent in CT and PET images. So, he visited our department for surgery treatment. We judged curative resection could be achieved for gastric cancer. Total gastrectomy, D2 and paraaortic lymphadenectomy, and cholecystectomy were performed. The histopathological examination of the resected specimen revealed the efficacy of chemotherapy was Grade 2b. The patient was discharge 14 days after the operation, and capecitabine plus trastuzumab was started as adjuvant chemotherapy, and the patient remains alive without recurrence 11 months after surgical treatment.

Rationale: Creutzfeldt-Jakob disease (CJD) with a point mutation of valine to isoleucine at codon 180 of the prion protein gene (V180I) is the most frequent form of genetic CJD in Japan. However, peripheral nerve involvement, especially cardiac sympathetic denervation, has not been investigated in cases with V180I genetic CJD.We herein report a genetically confirmed case of V180I genetic CJD presenting with parkinsonism and cardiac sympathetic nerve denervation., Patient Concerns: The patient was a 79-year-old Japanese woman who presented with subacute progressive gait disturbance and cognitive impairment. Clinical diagnosis of Parkinson's disease (PD) with mild cognitive impairment was initially suspected based on parkinsonism, such as bradykinesia, rigidity and tremor, and reduced accumulation of cardiac meta-iodobenzylguanidine (MIBG) scintigraphy., Interventions: Based on parkinsonism and impaired cardiac MIBG findings, levodopa/decarboxylase inhibitor was administered up to 300 mg/day; however, her symptoms were not improved., Outcomes: Her motor and cognitive function progressively deteriorated., Diagnosis: Although the patient had no family history of CJD, genetic CJD was diagnosed according to extensive hyperintensities in the bilateral cortices on diffusion-weighted magnetic resonance images, positive tau protein and 14-3-3 protein in the cerebrospinal fluid and a V180I mutation with methionine homozygosity at codon 129 by prion protein gene analysis., Lessons: We should be aware that reduced uptake of cardiac MIBG scintigraphy in patients presenting with parkinsonism cannot confirm a diagnosis of PD. CJD should be considered when patients show a rapid progressive clinical course with atypical manifestations of PD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Brain metastasis from esophageal cancer is rare. Symptoms such as paralysis caused a decline in quality of life(QOL)and activity of daily life(ADL)and required emergency treatment. We report 2 cases in which QOL was improved by emergency resection for brain metastasis from esophageal carcinoma with paralysis. Case 1: A 50's male was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N2M0, Stage Ⅲ). Brain metastasis was detected owing to development of left hemiparesis. Craniotomy and tumorectomy were performed, left hemiparesis was improved. He died 10 months after diagnosis of brain metastasis due to progression of other metastatic lesions. Case 2: A 61-year-old female was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N1M0, Stage Ⅲ). She developed right hemiparesis 5 months after esophagectomy, admitted to our hospital. Brain and lung metastases were detected, craniotomy and tumorectomy and were performed, right hemiparesis was improved. Although systemic chemotherapy was administered, she died 10 months after diagnosis of brain metastasis due to progression of lung metastasis. Conclusion: Aggressive surgical treatments for brain metastasis were one good treatment option to maintain QOL and ADL.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from Wuhan in December 2019 and resulted in a severe outbreak of pneumonia (COVID-19). SARS-CoV-2 is transmitted through respiratory droplets produced by coughs or sneezes, as well as aerosols containing viral particles. Noninvasive positive pressure ventilation (NPPV) is widely used to support respiration in patients with neuromuscular diseases. However, NPPV is also an aerosol-generating procedure. Without appropriate precautions, the risk of spreading the virus is high in NPPV users infected with SARS-CoV-2. At home, self-quarantine is effective in protecting caregivers of patients using NPPV, whereas in hospitals, using a negative pressure room is preferred. As SARS-CoV-2 can survive on surfaces for several days, disinfecting the NPPV machine and the items frequently touched in the room is essential. Setting viral filters is useful for preventing virus transmission and keeping the inside of the NPPV machine clean. Caregivers must wear appropriate personal protective equipment. Furthermore, it should be paid attention to the potential transmission from asymptomatic SARS-CoV-2 carriers. During the current pandemic, it is necessary to minimize the risk of transmission among patients using NPPV.

Background: Falls are a primary cause of physical disability in older adults, making them a major public health problem. Locomotive syndrome risk assessments have proven to be simple to administer, practical, and useful as screening tools in detecting decreased mobility in middle-aged and elderly adults. The current prospective study investigated whether these tests were associated with future falls among elderly Japanese., Methods: This study was a two-year prospective observational study. A total of 1800 individuals (aged 65-79 years) who were without certification of long-term care or physical disability were initially invited through letters to participate in the study. Of these, 499 individuals (225 men, 274 women) agreed to participate and underwent baseline assessments. Demographic information, body function physical performance measurements, and locomotive syndrome risk tests [Stand-Up Test (SUT), Two-Step Test (TST), and the 25-question Geriatric Locomotive Function Scale (GLFS-25)] were assessed. Following baseline evaluation, we sent a follow-up questionnaire to assess fall history in the past two years. Participants were classified as either "non-fallers" or "fallers" (denoted by one or more falls). Multiple logistic regression was used to evaluate the association between falls and each factor by providing adjusted odds ratio estimates., Results: The follow-up questionnaire was returned by 399 participants, 54 of whom (13.5%) fell at least once during the two-year observation period. The multiple logistic regression analysis revealed that difficulty with standing on one leg from a 40-cm-high seat (a portion of the SUT) was a significant predictor of future falls (odds ratio = 2.20, 95%CI = 1.04-4.69, p = 0.04). A history of falling was also a risk factor of falls., Conclusion: Our results suggest that standing on one leg from a 40-cm-high seat is predictive of falling in older adults, even after adjustment for previous falls and other confounding variables., (Copyright © 2019. Published by Elsevier B.V.)

The linear ubiquitin chain assembly complex (LUBAC), which consists of HOIP, SHARPIN and HOIL-1L, promotes NF-κB activation and protects against cell death by generating linear ubiquitin chains. LUBAC contains two RING-IBR-RING (RBR) ubiquitin ligases (E3), and the HOIP RBR is responsible for catalysing linear ubiquitination. We found that HOIL-1L RBR plays a crucial role in regulating LUBAC. HOIL-1L RBR conjugates monoubiquitin onto all LUBAC subunits, followed by HOIP-mediated conjugation of linear chains onto monoubiquitin, and these linear chains attenuate the functions of LUBAC. The introduction of E3-defective HOIL-1L mutants into cells augmented linear ubiquitination, which protected the cells against Salmonella infection and cured dermatitis caused by reduced LUBAC levels due to SHARPIN loss. Our results reveal a regulatory mode of E3 ligases in which the accessory E3 in LUBAC downregulates the main E3 by providing preferred substrates for autolinear ubiquitination. Thus, inhibition of HOIL-1L E3 represents a promising strategy for treating severe infections or immunodeficiency.

We herein report a 76-year-old Japanese man with myelofibrosis who developed cryptococcal meningitis. After treatment for 5 months with ruxolitinib, the patient presented with fever and disturbance of consciousness. Marked nuchal stiffness was noted. The magnetic resonance imaging results of the brain were normal. Lumbar puncture showed an opening cerebrospinal fluid (CSF) pressure of 110 mm H2O, pleocytosis (85 mononuclear cells and 222 polymorphonuclear cells/μL), decreased CSF/serum glucose ratio (43%), and elevated protein (194 mg/dL). Blood and CSF cultures grew no bacteria or fungi. However, cryptococcal antigen was detected in the blood and CSF samples. We discontinued ruxolitinib and started administration of amphotericin B. His condition improved gradually 1 week after initiation of treatment. There have been only a few reports on cryptococcal meningitis associated with ruxolitinib. Physicians should consider the possibility of cryptococcal meningitis in patients receiving ruxolitinib.

Background: An early clinical differentiation between Parkinson's disease (PD) and multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) remains a challenge. The purpose of this study was to evaluate the usefulness of the combination use of midbrain-to-pontine ratio (M/P ratio) from magnetic resonance imaging (MRI) with cardiac 123 I-metaiodobenzylguanidine (MIBG) uptake for differentiating PD from MSA and PSP., Methods: Ninety-six parkinsonian patients (70 PD, aged 68.5 ± 9.5 years; 16 MSA, aged 67.9 ± 7.5 years; 10 PSP, aged 70.4 ± 9.4 years) who underwent MRI and cardiac MIBG scintigraphy were included in this study. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity for distinguishing PD from MSA and PSP patients. The diagnostic accuracy of these tests was also assessed among patients at the early disease stage (defined as patients with a disease duration of 3 years or less)., Results: The individual diagnostic sensitivity of the M/P ratio and cardiac MIBG scintigraphy was 87.1% and 67.1% in PD vs. MSA and 78.6% and 67.1% in PD vs. PSP, respectively. The diagnostic specificity of the M/P ratio and cardiac MIBG scintigraphy was 56.3% and 100% in PD vs. MSA and 70.0% and 90% in PD vs. PSP, respectively. With the optimal cutoff values, at least one positive result (either the M/P ratio or cardiac MIBG revealed abnormalities) improved sensitivity (95.7%) without decrease of specificity (56.3%) in PD vs. MSA, as well as in PD vs. PSP (100% sensitivity, 70.0% specificity). In contrast, both positive results of two tests had good specificity but low sensitivity in PD vs. MSA (60.0% sensitivity and 100% specificity) and in PD vs. PSP (47.1% sensitivity and 90% specificity). Similar trends were observed in early-stage patients., Conclusion: Although M/P ratio alone was potentially useful for distinguishing PD from MSA or PSP, the combined use with cardiac MIBG scintigraphy can further improve the diagnostic accuracy of PD from MSA or PSP., (© 2019 The Author(s).)

A 50-year-old woman was diagnosed as having pancreatic head cancer with multiple hepatic metastases. FOLFIRINOX therapy was initiated. After completing 18 courses of therapy, partial remission(PR)was achieved based on images, and surgery was then planed. The subtotal stomach-preserving pancreaticoduodenectomy and hepatic S7 partial resection were performed. Macroscopically, complete resection was achieved. Regarding pathological findings of the primary lesion and hepatic metastatic lesions, fibrous formation and hyalinizing condition induced by chemotherapy were noted; moreover, complete disappearance of cancer cells was detected. However, metastasis of poorly differentiated adenocarcinoma was detected in 12b lymph node tissue. One month after the surgery, postoperative adjunctive chemotherapy with S-1 was initiated. However, new hepatic metastasis was detected 3 months after the surgery. Although recurrence treatment was initiated, the disease progressed, and the patient died 11 months after the surgery.

Objectives: To clarify the prevalence and characteristics of pain associated with sarcopenia and to verify the usefulness of evaluation of pain for sarcopenia., Methods: In total, 759 community-dwelling people (aged 65-79 years) with or without sarcopenia and lower limb pain were classified into 4 groups (NSp, nonsarcopenia; NSpP, nonsarcopenia with pain; Sp, sarcopenia; and SpP, sarcopenia with pain). Body composition, motor function, history of fractures since age 50 years, and number of falls in the past 1 year were compared between the groups., Results: Participant proportions by group were: NSp, 53.9%; NSpP, 42.8%; Sp, 1.3%; and SpP, 2.0%. Participants with lower limb pain showed low single leg standing, walking speed, and 2-step value scores and high 25-question Geriatric Locomotive Functional Scale (GLFS-25) score after adjusting for age, sex, body mass index, and presence of sarcopenia. The SpP group showed lower functional reach test and higher GLFS-25 scores than the Sp group. Regarding the history of fractures since 50 years of age and falls in past 1 year, a high retention rate of fracture was noted in the NSpP group. They also experienced significantly more falls in the past 1 year than those in the NSp group. The SpP group noted more falls and fractures although it was insignificant., Conclusions: The results indicate that participants with lower limb pain showed declining motor function and a high risk for falls and fractures. Sarcopenia could escalate this risk. Therefore, evaluating patients for both pain and sarcopenia may be useful for risk assessment and treatment.

Background: Simulation health care education is widely used in medical education and has great potential. However, scenario-based simulation health care education for preventing health care-associated infections has not been described., Methods: A single-center, prospective cohort study was conducted at Tokyo Medical University Hospital (1,015 beds), an acute care teaching hospital, from January 2011 to December 2014. Each training course was held every month and lasted 2 hours. Trainees put on and removed personal protective equipment under scenarios of standard precaution (2 scenarios) and contact precaution with methicillin-resistant Staphylococcus aureus (1 scenario), while considering the timing of hand hygiene. We determined the correlations between the participation rate in the simulation education and the use of alcohol-based hand disinfection and reduction of catheter-related bloodstream infection., Results: There were 1,077 trainees. The total participation rate for hospital staff, which increased gradually during the study period, was 76% by the end of the study. The overall correlation between the use of alcohol-based hand disinfection in the hospital and the course participation rate was significant (correlation coefficient, 0.97). An inverse correlation (-0.94) was observed for the relation between the training course participation rate and the incidence of catheter-related bloodstream infection., Conclusions: Our training course had a positive effect on hand hygiene. This study is the first effective scenario-based simulation health care education on hand hygiene and control of health care-associated infection., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteoporosis Liaison Service(OLS)is not only the fracture prevention of the onset, and the refracture prevention holds important positioning. For OLS activity in the hospitals of the fracture risk by FRAX grasp it, and it is important to evaluate the fall risk. What an interval, a motor function including the lower limbs muscular strength evaluate in a fall risk evaluation and TUG and walking speed temporarily for a fall risk evaluation for, the eye opening single leg right time to leave is desirable. It is a problem that an evaluation and treatment for osteoporosis are insufficient by recent DPC induction.

Dexrazoxane(DXZ)is a drug used for treating extravasation(EV)of anthracycline antitumor antibiotics based on 2 of its mechanisms of action through Topo II. In Japan, it has been used in approximately 150 patients as of January 2016, but there is no detailed report. Three DXZ treatments were carried out for 2 cases in our facilities. One case involved a patient's right forearm while 2 cases occurred involved the left and right forearms of each of the patients, and both were Grade 2(CTCAE v4.0). The EV healed in all cases, and surgical procedures were not needed. Moreover, chemotherapy was performed without extending the treatment period. One year 8 months after administration there was no recurrence in both cases, and skin disorders did not develop. In our hospital, DXZ is managed based on the regimen as well as the anticancer agents, and administration within 6 hours from extravasation was made possible by the cooperation of pharmaceutical wholesalers. Nurses and pharmacists who engage in chemotherapy are encouraged to participate in the study sessions of the hospital, it has been the effort to learn the day-to-day knowledge and technology. DXZ is effective in treating the EV of anthracycline antitumor antibiotics and may be well tolerated. To properly use DXZ by integrating these cases, it is necessary to verify its effectiveness and safety.

Stimulation with inflammatory cytokines such as TNF-α and IL-1 activates the canonical NF-κB pathway through the activation of the IKK complex. The mechanism underlying IKK activation has been extensively studied and the involvement of the ubiquitin system has been well documented. We have recently reported that a novel ubiquitin ligase complex, LUBAC is involved in the activation of the IKK complex. LUBAC consists of one catalytic subunit, HOIP and two accessory molecules, HOIL-1L and SHARPIN and activates the IKK complex by conjugating the linear polyubiquitin chains to NEMO (IKKγ), the regulatory subunit of IKK complex. In this chapter, we describe the protocol for the detection of the linear polyubiquitination of NEMO by the immunoblotting using anti-linear ubiquitin antibody.