Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report

Rationale:In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO.Patient concerns:A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome.Diagnoses:He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent.Interventions:Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min).Outcomes:Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient''s respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased.Lessons:TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.     

A successful case of varix of the left gastroepiploic vein preoperatively diagnosed by 3D-CT angiography and resected by laparoscopy: A case report

Introduction:Gastric varices can be present in up to 20% of patients with portal hypertension. However, a varix of the left gastroepiploic vein (LGV) is extremely rare. Surgery is required if bleeding occurs; thus, precise diagnosis is crucial. We present a successful case of preoperative diagnosis intraabdominal varix of the LGV using three-dimensional-computed tomography angiography (3D-CTA) followed by laparoscopic resection. This is the first report of a case with variant LGV. Our study demonstrates the efficacies of 3D-CTA and laparoscopic surgery for the diagnosis and safe resection of the intraabdominal varix, respectively.Patient concerns:A 74-year-old woman was referred to our department with a tumor in the abdominal cavity. On physical examination, no lumps were palpable in the upper abdomen.Diagnosis:The enhanced CT was revealed that the tumor was not enhanced in the early phase, but in the equilibrium phase. Moreover, 3D-CTA clearly revealed that the tumor was being supplied by the LGV. Thus, it was diagnosed as a variant of the LGV.Interventions:Surgical resection was performed laparoscopically as per the guidance of preoperative 3D-CTA findings. During surgery, a dark tumor was found along the gastroepiploic vessels, supplied by the LGV. The tumor was resected safely based on the preoperative information.Outcomes:Histopathological examination of the tumor showed accumulation of various vessels, but no malignant cells. Therefore, we made a final diagnosis of the tumor as an LGV varix. For follow-up, an annual CT examination was performed and after 3 years postoperation, no recurrence was observed.Conclusions:In the present case, we have achieved a successful preoperative diagnosis using 3D-CTA, and resection was safely accomplished using laparoscopy guided by preoperative anatomical information. This is the first report of an LGV variant. Appropriate management is crucial because bleeding is a catastrophic event. Therefore, imaging procedures such as 3D-CTA for diagnosis, followed by safe resection by laparoscopic surgery, are effective tools for the treatment of epiploic vein varices.     

Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami–Ogata syndrome)

Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, −1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29–70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith–Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name ‘Kagami–Ogata syndrome'' for UPD(14)pat and related conditions.     

Treatment of pediatric lymphoma in Japan: Current status and plans for the future

Results of pediatric lymphoma treatment have improved markedly over the past 30 years. In Hodgkin's lymphoma, the 5 year event‐free survival (EFS) was 81.5% in a retrospective study. In the ALB‐NHL03 study, the 5 year EFS according to clinical stage in patients with lymphoblastic T‐cell lymphoma (T‐LBL) was 70.6% for stage III and 88.9% for stage IV. In mature B‐cell lymphoma, the B‐NHL03 study indicated that the 4 year EFS according to treatment group was 94% for group 1, 98% for group 2, 84% for group 3, and 78% for group 4. Moreover, the 2 year EFS rate was 81% in Japanese advanced stage patients based on the international ALCL99 study. Thus, EFS >80% was achieved in any subtype of pediatric lymphoma. With regard to refractory or recurrent lymphoma, however, treatment methods for improvement of the survival rate in these patients still need to be developed. Also the difference between child, and adolescent and young adult patients still needs to be clarified, and treatment protocols developed. Although lymphoma treatment does not greatly change according to country, it does differ between other countries and Japan for some subtypes of lymphoma. In particular, the results of treatment of stage III T‐LBL in Japan are worse than those in the USA and Europe. The priority in future studies will be to collect data on these differences, and the reasons for these differences.     

Infective endocarditis associated with acute leukemia: Report of two cases

There have been few reports regarding infective endocarditis (IE) in patients with leukemia. In the first case, a 15‐year‐old girl with Down syndrome was diagnosed with acute lymphoblastic leukemia. On admission, methicillin‐sensitive Staphylococcus aureus (MSSA) was detected on blood culture. Echocardiography was performed because MSSA was detected repeatedly even after treatment. Vegetation in all of the atria and ventricles met the Duke criteria defining IE. She died of multiple organ failure 21 days after diagnosis. In the second case, an 11‐year‐old boy with acute myeloid leukemia underwent peripheral blood stem cell transplantation (PBSCT). He had fever 68 days after PBSCT, and methicillin‐resistant S. aureus (MRSA) was detected on blood culture. Echocardiography showed vegetation in the right atrium and ventricle. Daptomycin was administered for 7 weeks, and recurrence was not observed. IE should be considered when S. aureus bacteremia is documented even in patients with leukemia.     

An extramural gastrointestinal stromal tumor of the duodenum mimicking a pancreatic head tumor

We report the case of a 53‐year‐old woman with a gastrointestinal stromal tumor (GIST) of the duodenum that showed only extramural growth, mimicking a pancreatic tumor. Preoperatively, computed tomography (CT) and angiography revealed a hypervascular mass, 3.0 cm in diameter, in the pancreatic head. Hypotonic duodenography showed compression of the second and third portions of the duodenum by the pancreatic lesion. Endoscopic examination showed no specific mucosal abnormalities in the duodenal lumen. The pancreatic head tumor was diagnosed preoperatively as a nonfunctioning islet cell tumor of the pancreas, and the patient underwent pylorus‐preserving pancreaticoduodenectomy. A hard mass was palpated intraoperatively in the pancreatic head region, and neither peritoneal dissemination nor metastasis was detected. Histologically, the tumor was composed of spindle‐shaped cells with a fascicular growth pattern, and only a few mitotic features were seen. Immunohistochemically, most of the tumor cells were positive for c‐kit oncoprotein and CD34, but negative for alpha‐smooth muscle actin and S‐100 protein. Therefore, this neoplasm was finally diagnosed as a duodenal GIST of the uncommitted type. This is a rare case of a duodenal GIST with exclusively extramural growth mimicking a pancreatic head tumor.     

Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis

To determine whether “autoimmune hepatitis type IIb” should be categorized as a subgroup of autoimmune hepatitis, we conducted a clinicopathological study of 25 adult Japanese patients who were positive for anti-liver/kidney microsome-1 (anti-LKM-1) antibody and infected with the hepatitis C virus (HCV). Anti-LKM-1 was determined by indirect immunofluo-rescence and by the double immunodiffusion assays we have developed. Twenty-two patients did not present any unusual symptoms or any associated diseases during the course of their chronic HCV infection. The spectrum of HCV genotypes of these patients did not significantly differ from that of anti-LKM-1-negative Japanese patients with chronic hepatitis C. Histological examination of liver biopsy specimens showed the usual characteristics of chronic hepatitis C and lack of characteristics of autoimmune hepatitis type I. No disease-specific HLA haplotypes were noted, and HLA-DR4, which is detectable in 88.7% of Japanese patients with autoimmune hepatitis type I, was detected in only 50.0% of our group, the same rate as the background frequency. Prednisolone was effective in none of the six patients treated, but interferon was effective in six of ten treated patients (60%). From these results, we conclude that “autoimmune hepatitis type IIb” should not be categorized as autoimmune hepatitis, and that this subgroup is essentially chronic hepatitis C in which an autoantibody has been produced during the course of chronic HCV infection.     

Vanadyl‐TrBR4‐Catalyzed Oxidative Polymerization of Diphenyl Disulfide

A newly established catalyst system for oxygen‐oxidative polymerization of diphenyl disulfide is reported. Combination of vanadyl compounds (e.g., VO(acac)₂) and triphenylmethylium tetrakis(pentafluorophenyl)borate (TrB(C₆F₅)₄) proceeds the polymerization to give poly(1,4‐phenylene sulfide) (PPS) at 100 °C. When triphenylmethylium tetrafluoroborate (TrBF₄) is applied with vanadyl tetraphenylporphyrin (VO(TPP)) or N,N′‐(ethylenebis(salicylideneaminato))oxovanadium (VO(salen)), PPS is also given via polymerization under conditions near 160 °C. Combination of the vanadyl complex and the borate affords the first protic‐acid‐free catalytic system for the polymerization of the disulfide, suggesting the overall reaction to produce PPS and H₂O from O₂ and protons that are eliminated from the monomer.

     

Significance of intravascular ultrasound and exercise stress echocardiography in diagnosis of exercise-induced vasospastic angina at the site of moderate stenosis

Recently, exercise-induced spastic coronary artery occlusion at the site of moderate stenosis, which Prinzmetal’s angina or cardiac syndrome X does not cover, was reported. Multi-modality imaging is important for the diagnosis of coronary artery disease with a complex ischemic mechanism. However, the previous report did not include findings from intracoronary imaging at the site of moderate coronary stenosis. We report a case of exercise-induced vasospastic angina at the site of moderate stenosis, where multi-modality imaging, including exercise stress echocardiography and intravascular ultrasound, was utilized to make a definitive diagnosis and investigate underlying causes.     

Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.