Reproducibility and prognostic significance of area of residual tumor (ART) in post-neoadjuvant resections of pancreatic ductal adenocarcinoma.

BACKGROUND: The pathologic assessments of tumor response after neoadjuvant chemoradiotherapy (NACRT) are critical to improving the prognostic stratification for patients with pancreatic ductal adenocarcinoma (PDAC). Here we clarified the utility of our new grading system based on the area of residual tumor (ART) as compared to existing systems, such as the College of American Pathologists (CAP) and MD Anderson (MDA) score. METHODS: Eight reviewers individually evaluated the tumor regression grade of 30 patients with PDAC based on three types of grading systems. The interobserver concordance and clinicopathological characteristics were compared between the three systems. RESULTS: The interobserver concordance (kappa value) of the ART, CAP, and MDA score were 0.61, 0.48, and 0.53, respectively. Discrepant cases, which were 27% of the cases, exhibited smaller tumor and tumor bed sizes than concordant cases. The reduction in tumor size evaluated by microscopy showed a correlation with the rate of change in carcinoembryonic antigen (CEA) level, CA19-9 level, and tumor size on computed tomography (CT). The ART score was correlated with the tumor size on CT before and after NACRT and disease-free survival. The CAP and MDA scores were not associated with prognosis. CONCLUSION: The ART grading system may be the most practical system to assess the tumor response in post-NACRT resections of PDAC.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Serum Angiopoietin-Like Protein 2 and NT-Pro BNP Levels and Their Associated Factors in Patients with Chronic Heart Failure Participating in a Phase III Cardiac Rehabilitation Program.

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Examination of Anterior Leaflet Pseudoprolapse Causing Severe Mitral Regurgitation and Its Ideal Surgical Procedure.

BACKGROUND: The aim of this study is to evaluate severe mitral regurgitation caused by so called atrial leaflet "pseudoprolapse" and verify the effect of simple annular stabilization. METHODS: One-hundred-twenty-two patients underwent surgery for severe mitral regurgitation at our institute between January 2015 to July 2018. Of those, 32 cases diagnosed as anterior leaflet prolapse that underwent mitral repair were analyzed. Ten cases with pseudoprolapse, which is defined as anterior leaflet prolapse without dropping into the left atrium beyond the annular line causing eccentric regurgitation flow directed to the posterior atrium, were classified as the Pseudoprolapse Group. The other 22 cases had obvious anterior leaflet prolapse dropping into the left atrium; these cases were classified as the True Prolapse Group. We compared clinical findings between the 2 groups and reviewed pseudoprolapse cases. RESULTS: Patients in the Pseudoprolapse Group had lower ejection fraction and lower regurgitation volume than those in the True Prolapse Group. A2 lesion as main inflow of regurgitation was more included in the Pseudoprolapse Group. All but one patient in the Pseudoprolapse Group received only simple annuloplasty, and all patients in the True Prolapse Group received leaflet repair and annuloplasty. In both groups, mid-term regurgitation grade and the reoperation rate were satisfactory. In the Pseudoprolapse Group, 6 cases were clarified as atrial functional mitral regurgitation, and 4 cases were considered to have focal posterior leaflet tethering. CONCLUSIONS: Pseudoprolapse cases could be characterized by low ejection fraction, low regurgitation volume, and A2 prolapse. For most cases with pseudoprolapse, simple annuloplasty may be enough, however further study is needed.

[Thrombotic and Bleeding Risks of Patients on Antiplatelet Therapy Undergoing Major Abdominal Malignancy Surgery].

BACKGROUND: Controversies still exist whether to continue or withdraw aspirin (ASA) perioperatively. This study was performed to determine whether patients on preoperative antiplatelet therapy (APT) benefit from continuing ASA in terms of thrombotic and bleeding risk prevention. METHODS: Among 307 consecutive patients who were on APT preoperatively for the secondary prevention of cardiovascular disease and who underwent elective major abdominal malignancy surgery, 148 patients had all the preoperative APT withdrawn and the remaining 159 patients continued only ASA. Comparisons were made between the 2 groups regarding the rate and the amount of exogenous blood transfusion as well as the incidence of thromboembolic events (TEEs) within 1 month after surgery. RESULTS: The incidence of perioperative TEEs of the APT withdrawn group was significantly higher than that of the ASA group (6.2% vs 0%, P = 0.005), while the rate and the amount of exogenous blood transfusion were not different each other (23.6% vs 17.0%, P = 0.146 and 4 units vs 4 units, P = 0.544, respectively). CONCLUSIONS: Considering the relatively low bleeding risk when continued and the increased thrombotic risk after withdrawal, ASA should be continued perioperatively in patients undergoing major abdominal malignancy surgery.

Visualization of microvessels by angiography using inverse-Compton scattering X-rays in animal models.

The fundamental performance of microangiography has been evaluated using the S-band linac-based inverse-Compton scattering X-ray (iCSX) method to determine how many photons would be required to apply iCSX to human microangiography. ICSX is characterized by its quasi-monochromatic nature and small focus size which are fundamental requirements for microangiography. However, the current iCSX source does not have sufficient flux for microangiography in clinical settings. It was determined whether S-band compact linac-based iCSX can visualize small vessels of excised animal organs, and the amount of X-ray photons required for real time microangiography in clinical settings was estimated. The iCSX coupled with a high-gain avalanche rushing amorphous photoconductor camera could visualize a resolution chart with only a single iCSX pulse of ∼3 ps duration; the resolution was estimated to be ∼500 µm. The iCSX coupled with an X-ray cooled charge-coupled device image sensor camera visualized seventh-order vascular branches (80 µm in diameter) of a rabbit ear by accumulating the images for 5 and 30 min, corresponding to irradiation of 3000 and 18000 iCSX pulses, respectively. The S-band linac-based iCSX visualized microvessels by accumulating the images. An iCSX source with a photon number of 3.6 × 10(3)-5.4 × 10(4) times greater than that used in this study may enable visualizing microvessels of human fingertips even in clinical settings.

Entomopathogenic fungus Beauveria bassiana-based bioinsecticide suppresses severity of powdery mildews of vegetables by inducing the plant defense responses.

The entomopathogenic fungus Beauveria bassiana is used commercially as a microbial insecticides against a wide range of agricultural insect pests. Some strains of B. bassiana protect the plants from pathogens, but the underlying mechanisms are largely unknown. Here, we found that prophylactic sprays of commercial bioinsecticide Botanigard on cucumber, tomato, and strawberry plants suppressed the severity of economically damaging powdery mildews. On leaf surfaces, hyphal elongation and spore germination of cucumber powdery mildew, Podosphaera xanthii, were inhibited, but B. bassiana strain GHA, the active ingredient isolated from Botanigard, only inhibited hyphal elongation but had no effect on spore germination of P. xanthii. In addition, strain GHA suppressed powdery mildew symptoms locally, not systemically. Treatment with Botanigard and strain GHA induced a hypersensitive response (HR)-like cell death in epidermal cells of the cucumber leaves in a concentration-dependent manner and inhibited penetration by P. xanthii. Transcriptome analysis and mass spectrometry revealed that GHA induced expression of salicylic acid (SA)-related genes, and treatment with Botanigard and GHA increased the SA level in the cucumber leaves. In NahG-transgenic tomato plants, which do not accumulate SA, the biocontrol effect of tomato powdery mildew by GHA was significantly reduced. These results suggested that B. bassiana GHA induces SA accumulation, leading to the induction of HR-like cell death against powdery mildew and subsequent suppression of fungal penetration. Thus, Botanigard has the potential to control both insect pests and plant diseases.

Platelet aggregation with various morphologies of neutrophils in arterial thrombus in a patient with Coronavirus disease: a case report.

Arterial thromboembolism is a life-threatening condition in COVID-19 patients; however, the mechanism of hypercoagulopathy remains unknown. A 62-year-old man with a history of obesity was diagnosed with COVID-19 pneumonia. After hospitalisation, unfractionated heparin was administered because of increased D-dimer levels; nevertheless, an arterial embolism in the left lower limb developed on the following day. Enhanced computed tomography revealed an occluded left iliac artery and intra-aortic thrombus at the juxtarenal level. Urgent thrombectomy was performed. On post-operative day 6, coumadin was initiated to treat the remaining thrombus. The patient was discharged without any complications. The removed thrombus pathologically presented platelet aggregation and degenerated neutrophils that were in various time axes; some neutrophils had clear margins of nuclear membrane, whereas others had pyknotic and fragment nuclei. We believe that the platelet formation and the neutrophils in several time axes could be key factors in promoting thrombus formation in COVID-19 patients.

Endovascular Repair for Abdominal Aneurysm with Concomitant Aortoiliac Vein Fistula Diagnosed by Four-Dimensional Computed Tomography.

A 78-year-old man complaining of left leg swelling was diagnosed with an abdominal aortic aneurysm with an irregular margin. A four-dimensional computed tomography (CT) showed an aortoiliac vein fistula. An AFX stent graft was urgently implanted, and a Viabahn VBX was inserted into the left iliac vein. The aneurysmal sac was embolized. After the procedure, enhanced CT confirmed a patent stent graft without any endoleak or fistula. The patient was discharged ambulatory. An aortoiliac vein fistula is a differential diagnosis for leg edema, and a four-dimensional CT is beneficial in diagnosing the condition.

Acute Limb Ischemia Caused by Embolus of Primary Lung Cancer Complicating Trousseau's Syndrome.

Limb ischemia caused by tumor embolus is rare. In this study, we report the case of a 77-year-old woman who suffered from acute ischemic limb. Computed tomography showed a tumor in the right bronchus invading the left atrium. The tumor fragments scattered resulting in the occlusion of the right iliac artery. The excluded embolus was revealed as a squamous cell carcinoma. Regarding the popliteal venous thrombus, Trousseau's syndrome was complicated. The patient was discharged without any complications. We believe that advanced lung cancer is a differential diagnosis of acute ischemic limbs and that successful limb rescue contributed to a patient's quality of life.

Establishment of a mouse model of pancreatic cancer using human pancreatic cancer cell line S2-013-derived organoid.

A well-established preclinical model of pancreatic cancer needs to be established to facilitate research on new therapeutic targets. Recently established animal models of pancreatic cancer, including patient-derived tumor models and organoid models, are used for pre-clinical drug testing and biomarker discovery. These models have useful characteristics over conventional xenograft mouse models based on cell lines in preclinical studies, but still cannot accurately predict the clinical outcomes of new treatments and have not yet been broadly implemented in research. We employed pancreatic cancer organoid culture methods using the pancreatic cancer cell line S2-013, and performed pathological and immunohistochemical analyses to characterize tumor xenografts obtained from a mouse model implanted with S2-013 cell line-derived organoids. Serum levels of the pancreatic cancer tumor marker CA19-9 were measured by ELISA. We generated human pancreatic cancer organoids using a co-culture of S2-013 cells, human endothelial cells derived from human umbilical vein endothelial cells, and human mesenchymal stem cells, and established a mouse model with subcutaneously transplanted human pancreatic cancer organoids (S2-013-organoid model). Although blood clotting crater-like formation developed in the middle of subcutaneous xenografts in the S2-013-conventional model, created by subcutaneously injecting S2-013 cells into the right flank of nude mice, the size of xenografts in the S2-013-organoid model gradually increased without crater-like formation. Importantly, tumor xenografts obtained from the S2-013-organoid model exhibited a clinical human pancreatic cancer tissue-like cellular morphology, tissue architecture, and polarity, and actively formed cancer stroma containing mature blood vessels with the high expression of the vascular tight junction marker CD31. In subcutaneous xenografts of S2-013-conventional mice, no blood vessel density or widely expanding areas of necrotic regions were present. Consequently, serum levels of CA19-9 in the S2-013-organoid model correlated with tumor volumes. In addition, epithelial-mesenchymal transition, the conversion of epithelial cells to the mesenchymal phenotype, was observed in tumor xenografts of the S2-013-organoid model. The S2-013-organoid model provides tumor xenografts consisting of clinical human pancreatic cancer-like tissue formation with the effective development of vascularized stroma, and may be valuable for facilitating studies on pre-clinical drug testing and biomarker discovery.

Murine remote ischemic preconditioning upregulates preferentially hepatic glucose transporter-4 via its plasma membrane translocation, leading to accumulating glycogen in the liver.

AIMS: We previously showed that hindlimb ischemia-reperfusion (IR) enhanced glucose uptake in the liver through the activation of the parasympathetic nervous system. Although we suggested that the key glucose transporter (GLUT) in this hepatic glucose uptake was GLUT4 by western blotting, the molecular weight of GLUT4 was nearly the same as that of GLUT2, which is predominantly expressed in the liver. We primarily conducted a histological evaluation to determine whether IR specifically accelerates the overexpression of GLUT4, rather than GLUT2, in the hepatocytes in vitro and in vivo. MAIN METHODS: A total of 54 male C57BL/6J mice were used and subjected to 3 min hindlimb ischemia repeated three times with 3 min interval. Focusing on the area connecting portal and central veins, the GLUT4 and GLUT2 expression in the hepatocytes were examined by real-time PCR and immunohistochemically. Moreover, the alteration of GLUT4 and GLUT2 expression by acetylcholine in the primary hepatocytes were examined by immunofluorescence. KEY FINDINGS: IR significantly upregulated the GLUT4, rather than GLUT2, expression in both mRNA and protein in the liver. Histological examination revealed marked glycogen storage in zone1, the periportal area, coincident with the enhanced GLUT4 immunoreactivity, in the IR-treated liver. Incubation of primary hepatocytes with acetylcholine induced the appearance of GLUT4 on the membrane peripheries. SIGNIFICANCE: The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage in zone1 through energy production linked with increased glucose preference.

Reconstruction for rupture of profunda femoris artery aneurysm in a patient with sarcopenia.

Profunda femoris artery aneurysm (PFAA) is rare and has a high incidence of rupture. Herein, we report the case of an 80-year-old man who developed sarcopenia after gastric surgery. The patient presented to our hospital with a reddish thigh and was diagnosed with PFAA rupture. We performed aneurysmectomy and graft interposition in emergency. Postoperative enhanced computed tomography revealed an interposed graft, and the patient was discharged on postoperative Day 7. We considered that the PFAA patients with sarcopenia has a high risk of rupture because the muscles surrounding the profunda femoris artery became weak, and should be followed-up closely.

Remote simulator training of coronary artery bypass grafting during the coronavirus disease 2019 pandemic.

OBJECTIVES: The coronavirus disease 2019 pandemic presents in-person exposure risk during surgical education. We aimed to validate the feasibility of fully remote faculty-supervised surgical training sessions focused on coronary artery bypass grafting using a synthetic simulator and online videochat software. METHODS: This observational study organized 24 sessions of 2-hour remote training. Each session involved 3 trainees, 1 faculty member, and 1 host. A total of 70 trainees and 24 faculty members were enrolled. The participants joined the remote sessions via online videochat and performed focused training in coronary artery anastomosis using a commercially available simulator. A survey was conducted to validate the feasibility of the remote sessions. Performance improvement of the trainees who repeatedly participated (n = 13) were analyzed comparing initial and final scores of various performance indicators. RESULTS: All trainees and faculty members were satisfied with the efficacy of the remote session. Additionally, most trainees (79%) and faculty members (95%) agreed that the remote training sessions were equivalent to conventional onsite training seminars. A significant improvement between initial and last sessions was observed in the scoring components of near side (3.4 ± 1.0 vs 4.1 ± 0.9; P = .02), far side (3.3 ± 0.8 vs 3.9 ± 0.8; P = .03), external appearance (3.5 ± 0.8 vs 4.2 ± 0.7; P = .01), and internal appearance (2.8 ± 0.9 vs 4.0 ± 0.9; P = .004). CONCLUSIONS: Faculty-supervised remote surgical training sessions were executed with satisfactory results. This methodology may have important implications for surgical education during the coronavirus disease 2019 pandemic.

Murine remote ischemic preconditioning suppresses diabetic ketoacidosis by enhancing glycolysis and entry into tricarboxylic acid cycle in the liver.

AIMS: Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice. MAIN METHODS: Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay. KEY FINDINGS: Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR. SIGNIFICANCE: These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.

Superficial Angiomyxoma of the Nipple in a Japanese Woman: A Case Report and Review of Literature.

Superficial angiomyxoma is a rare, benign, multilobulated cutaneous tumor composed of stellate and spindle cells, a prominent myxoid matrix, and numerous blood vessels. Superficial angiomyxoma may be indistinguishable from cutaneous lesions of the Carney complex, although superficial angiomyxoma can occur independently of the complex. In this article, we present the case of a 39-year-old Japanese woman with a 40 × 30 mm, focally ulcerated, polypoid superficial angiomyxoma on the left nipple without any evidence of Carney complex. The development of superficial angiomyxoma on the nipples in a patient without the Carney complex is extremely rare. Indeed, only 3 cases of superficial angiomyxoma arising on the nipple have been reported to date, and this is the first such report in Japan. In such cases, the majority of superficial angiomyxoma of the nipples develop in premenopausal women. The possibility of superficial angiomyxoma should be considered for all polypoid nipple lesion, particularly in premenopausal women, and complete excision with follow-up observation should be performed.

Pulmonary artery banding for initial treatment of ventricular septal rupture.

Ventricular septal rupture (VSR) is a serious and fatal mechanical complication after acute myocardial infarction. Emergent or urgent, surgical/transcatheter intervention is necessary to treat VSR, though the outcome is not favorable. We performed temporary pulmonary artery banding (PAB) in an 85-year-old man who presented with chest pain to adjust the shunt flow through the VSR, which prevented further pulmonary edema and delayed the timing of surgical repair. There has been no report showing successful PAB performed for VSR after myocardial infarction.

Coronary-Pulmonary Artery Fistula Ligation and Mitral Valve Repair Through a Mini-Thoracotomy Approach.

A 39-year-old man with severe mitral regurgitation was referred to our institution for surgical evaluation. During preoperative workup, a coronary-pulmonary artery fistula was incidentally found by computed tomography. After multidisciplinary cardiac team discussion, the decision was made to proceed with coronary-pulmonary artery fistula ligation and mitral valve repair through a mini-thoracotomy approach. Cardiopulmonary bypass was initiated with femoral vessels. A mini-thoracotomy was made in the fourth intercostal space. First, mitral valve repair with posterior leaflet folding and ring annuloplasty was done. The coronary-pulmonary artery fistula was running on the roof of the left atrium and was ligated with metal clips under thoracoscopic vision. Postoperative computed tomography showed no residual fistula.

Open brachiocephalic artery stent for static obstruction caused by acute type A aortic dissection.

Brachiocephalic artery dissection complicated by acute type A aortic dissection occasionally causes cerebral malperfusion. Although immediate central aortic repair has been the standard treatment for aortic dissection, dissection in supra-aortic vessels frequently remains after the surgery. The residual brachiocephalic artery dissection is reported to be associated with late neurological events. Therefore, additional intervention for brachiocephalic artery dissection during central aortic repair should be considered in selected cases. In this report, we describe two cases requiring open brachiocephalic artery stenting simultaneous with central aortic repair. There were no neurological or stent induced complications at latest follow-up.

A case of pulmonary artery sarcoma that was initially mis-diagnosed as pulmonary embolism.

Pulmonary artery sarcoma is a rare and highly malignant neoplasm. Early diagnosis and a multidisciplinary approach including surgical treatment and optimal medical therapy could prolong survival. Since the clinical symptoms and imaging findings of pulmonary artery sarcoma mimic pulmonary embolism, definitive diagnosis and surgical intervention are often delayed. In this report, a case of pulmonary artery sarcoma that was initially misdiagnosed as pulmonary embolism is presented.