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Currently, individuals leave a digital trace of their activities when they use their smartphones, social media, mobile apps, credit card payments, Internet surfing profile, etc. These digital activities hide intrinsic usage patterns, which can be extracted using sequential pattern algorithms. Sequential pattern mining is a promising approach for discovering temporal regularities in huge and heterogeneous databases. These sequences represent individuals’ common behavior and could contain sensitive information. Thus, sequential patterns should be sanitized to preserve individuals’ privacy. Hence, many algorithms have been proposed to accomplish this task. However, these techniques add noise to the candidate support before they are validated as, frequently, and thus, they cannot be applied without having access to all the users’ sequences data. In this paper, we propose a differential privacy graph-based technique for publishing frequent sequential patterns. It is applied at the post-processing stage; hence it may be used to protect frequent sequential patterns after they have been extracted, without the need to access all the users’ sequences. To validate our proposal, we performed a detailed assessment of its utility as a pattern mining algorithm and calculated the impact of the sanitization mechanism on a recommender system. We further evaluated its information loss disclosure risk and performed a comparison with the DP-FSM algorithm.

Synthesis of novel 7,7-difluoroprostacyclin and 15-deoxy-15,15-difluoro-PGF2? derivatives will be presented. These compounds show high affinity to prostaglandin receptors and potent biological activities.

Background: Hematoma expansion (H-Ex) in small-/medium-sized acute epidural hematoma (AEDH) cases upon emergency admission is critical. Predicting H-Ex can lead to early surgical interventions, improving outcomes, and eliminating the need to check for expansion via computed tomography (CT). This study aimed to identify the most reliable predictors of AEDH expansion., Methods: We retrospectively collected data from patients with pure AEDH not requiring surgical treatment upon emergency admission from 2012 to 2022. We assessed clinical and laboratory data, time from injury to the first CT, and time to follow-up CT. Factors predictive of H-Ex on the second follow-up CT, including the leakage sign (LS), were analyzed., Results: A total of 23 patients with pure AEDH without surgery at admission were included, and LS was positive in 18. Thirteen patients showed H-Ex. The H-Ex group showed a significantly higher rate of positive LS and a lower mean platelet count than the group without H-Ex. LS's predictive value for AEDH expansion showed 100% sensitivity and 50% specificity. All patients with negative LS and normal platelet counts showed no H-Ex. Analyzing the time from injury to the first CT suggested that LS (+) within 120 minutes strongly predicted H-Ex. Reconstructed three-dimensional images of the leakage point on the skull revealed multiple mottled bleeding points on the dural surface., Conclusions: LS can predict H-Ex in patients with pure AEDH for whom emergency surgery is unnecessary at admission. The time from injury and platelet counts must also be considered., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis., Procedure: To overcome this difficulty, we performed an assay for transposase-accessible chromatin with sequencing (ATAC-seq) in 10 AML patients with various gene alterations. ATAC-seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq analysis revealed increased accessibility of the DOCK1 gene in patients with AML harboring poor prognostic factors. Following the ATAC-seq results, quantitative reverse transcription polymerase chain reaction was used to measure DOCK1 gene expression levels in 369 pediatric patients with de novo AML., Results: High DOCK1 expression was detected in 132 (37%) patients. The overall survival (OS) and event-free survival (EFS) among patients with high DOCK1 expression were significantly worse than those patients with low DOCK1 expression (3-year EFS: 34% vs. 60%, p < .001 and 3-year OS: 60% vs. 80%, p < .001). To investigate the significance of high DOCK1 gene expression, we transduced DOCK1 into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells., Conclusions: Our results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti-cancer agents in patients with AML with high DOCK1 expression., (© 2024 Wiley Periodicals LLC.)

Background: Very few studies have examined the association between contrast-enhanced computed tomography (CT) findings observed in portal venous gas (PVG) and pneumatosis intestinalis (PI) and the underlying diseases in these conditions., Objectives: In this study, we analyzed this association and report the findings for predicting mortality., Materials and Methods: Overall, 50 patients diagnosed with PVG or PI, observed on contrast-enhanced CT, underwent treatment at our hospital. Based on the underlying disease, we divided the patients into three groups, those with ischemic disease, infectious disease, or gastrointestinal dilatation. Furthermore, cases that underwent surgical treatment or needed surgery but were inoperable were assigned to the high risk group (n=16) and patients who received conservative treatment were assigned to the low risk group (n=34). We reviewed the patients' medical charts, laboratory data, and CT images retrospectively, and analyzed the relationship between CT findings, underlying disease, and association with the high risk or low risk group in each case., Results: Poor enhancement of the intestinal wall, mesenteric fat stranding, extrahepatic PVG, advanced age, and renal disease were significantly associated with ischemic disease (p=0.02, p=0.02, p=0.005, p=0.008 and p=0.049, respectively). PI alone was strongly associated with gastrointestinal dilatation (p=0.009). Patients in the low risk group had more favorable outcomes with conservative treatment. In multivariate analysis, extrahepatic PVG was the only factor associated with the high risk group (p=0.002)., Conclusion: Extrahepatic PVG associated with ischemic disease was the strongest predictive factor of mortality. Other CT findings, though useful in diagnosing the underlying disease, were not significant predictive factors.

Abstract: Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes. However, the molecular basis for refractoriness and relapse and the full spectrum of driver mutations in ML-DS remain largely unknown. We conducted a genomic profiling study of 143 TAM, 204 ML-DS, and 34 non-DS acute megakaryoblastic leukemia cases, including 39 ML-DS cases analyzed by exome sequencing. Sixteen novel mutational targets were identified in ML-DS samples. Of these, inactivations of IRX1 (16.2%) and ZBTB7A (13.2%) were commonly implicated in the upregulation of the MYC pathway and were potential targets for ML-DS treatment with bromodomain-containing protein 4 inhibitors. Partial tandem duplications of RUNX1 on chromosome 21 were also found, specifically in ML-DS samples (13.7%), presenting its essential role in DS leukemia progression. Finally, in 177 patients with ML-DS treated following the same ML-DS protocol (the Japanese Pediatric Leukemia and Lymphoma Study Group acute myeloid leukemia -D05/D11), CDKN2A, TP53, ZBTB7A, and JAK2 alterations were associated with a poor prognosis. Patients with CDKN2A deletions (n = 7) or TP53 mutations (n = 4) had substantially lower 3-year event-free survival (28.6% vs 90.5%; P < .001; 25.0% vs 89.5%; P < .001) than those without these mutations. These findings considerably change the mutational landscape of ML-DS, provide new insights into the mechanisms of progression from TAM to ML-DS, and help identify new therapeutic targets and strategies for ML-DS., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objective: Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition., Methods: The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed., Results: This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C., Conclusions: This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Autoimmune lymphoproliferative syndrome (ALPS) is a disease of lymphocyte homeostasis caused by FAS-mediated apoptotic pathway dysfunction and is characterized by non-malignant lymphoproliferation with an increased number of TCRαβ+CD4-CD8- double-negative T cells (αβDNTs). Conversely, RAS-associated leukoproliferative disease (RALD), which is caused by gain-of-functional somatic variants in KRAS or NRAS, is considered a group of diseases with a similar course. Herein, we present a 7-year-old Japanese female of RALD harboring NRAS variant that aggressively progressed to juvenile myelomonocytic leukemia (JMML) with increased αβDNTs. She eventually underwent hematopoietic cell transplantation due to acute respiratory distress which was caused by pulmonary infiltration of JMML blasts. In general, αβDNTs have been remarkably increased in ALPS; however, FAS pathway gene abnormalities were not observed in this case. This case with RALD had repeated shock/pre-shock episodes as the condition progressed. This shock was thought to be caused by the presence of a high number of αβDNTs. The αβDNTs observed in this case revealed high CCR4, CCR6, and CD45RO expressions, which were similar to Th17. These increased Th17-like αβDNTs have triggered the inflammation, resulting in the pathogenesis of shock, because Th17 secretes pro-inflammatory cytokines such as interleukin (IL)-17A and granulocyte-macrophage colony-stimulating factor. The presence of IL-17A-secreting αβDNTs has been reported in systemic lupus erythematosus (SLE) and Sjögren's syndrome. The present case is complicated with SLE, suggesting the involvement of Th17-like αβDNTs in the disease pathogenesis. Examining the characteristics of αβDNTs in RALD, JMML, and ALPS may reveal the pathologies in these cases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients., Aim: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC., Discussion: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Background: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma., Methods: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses., Results: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance., Conclusion: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Background: Surgical site infection (SSI) is one of the most important complications of surgery for gastroenterological malignancies because it leads to a prolonged postoperative hospital stay and increased inpatient costs. Furthermore, SSI can delay the initiation of postoperative treatments, including adjuvant chemotherapy, negatively affecting patient prognosis. Identifying the risk factors for SSI is important to improving intra- and postoperative wound management for at-risk patients., Methods: Patients with gastroenterological malignancies who underwent surgery at our institution were retrospectively reviewed and categorized according to the presence or absence of incisional SSI. Clinicopathological characteristics such as age, sex, body mass index, malignancy location, postoperative blood examination results, operation time, and blood loss volume were compared between groups. The same analysis was repeated of only patients with colorectal malignancies., Results: A total of 528 patients (330 men, 198 women; mean age, 68 ± 11 years at surgery) were enrolled. The number of patients with diseases of the esophagus, stomach, small intestine, colon and rectum, liver, gallbladder, and pancreas were 25, 150, seven, 255, 51, five, and 35, respectively. Open surgery was performed in 303 patients vs. laparoscopic surgery in 225 patients. An incisional SSI occurred in 46 patients (8.7%). Multivariate logistic regression analysis showed that postoperative hyperglycemia (serum glucose level ≥140 mg/dl within 24 h after surgery), colorectal malignancy, and open surgery were independent risk factors for incisional SSI. In a subgroup analysis of patients with colorectal malignancy, incisional SSI occurred in 27 (11%) patients. Open surgery was significantly correlated with the occurrence of incisional SSI ( P  = 0.024)., Conclusions: Postoperative hyperglycemia and open surgery were significant risk factors for SSI in patients with gastroenterological malignancies. Minimally invasive surgery could reduce the occurrence of incisional SSI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yamamoto, Yoshitomi, Oshimo, Nishikawa, Hisano, Nakano, Kawai, Okuchi, Iguchi, Tanaka, Fukuda, Taura and Terajima.)

Background: Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions. Anterior commissurotomy (AC) has been historically performed with CC. However, the efficacy and safety of adding AC to CC remain unknown., Objective: To describe the surgical technique of extraventricular AC and retrospectively investigate its clinical efficacy and safety by assessing patients who underwent CC with and without AC., Methods: AC has been added to CC at our institution since 2018. Fifty-five consecutive patients who received total callosotomy from 2016 to 2020 were included and categorized into 2 groups: 26 patients with additional AC and 29 patients without additional AC. Seizure outcome 1 year after surgery were compared between groups for assessing the efficacy of adding AC. The perioperative factors were compared for assessing the safety and feasibility., Results: Seizure reduction rate (50% and 60%; P = .60) and disappearance of drop attacks (42% and 58%; P = .25) were not significantly different between CC and CC + AC groups. No statistical group differences were found in intraoperative estimated blood loss, number of days to first oral intake, duration of postoperative intravenous hydration, and length of hospital stay., Conclusion: Disconnection of the anterior commissure is a feasible and relatively safe procedure. This study failed to show the significant efficacy of adding AC to CC. However, further investigation is needed to prove its efficacy in ameliorating epilepsy., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background/aim: Malignant biliary obstruction (MBO) is a life-threatening condition. We aimed to investigate the outcome of salvage percutaneous transhepatic biliary drainage (PTBD) in patients with unresectable MBO due to failure of management by endoscopic retrograde cholangiopancreatography (ERCP) and/or prior surgical bypass., Patients and Methods: Fifty-two consecutive patients (mean age, 69 years; 44.2% women) underwent salvage PTBD between 2013 and 2020., Results: The median overall survival rate was 4.2 months, with a 95% confidence interval (CI) of 1.9-5.7. The median overall survival (OS) were 11.1 months and 1.9 months for patients who underwent chemotherapy (n=17) and best supportive care (n=35), respectively (p=0.0005). Independent factors predicting poor outcome were best supportive care, with a hazard ratio (HR) of 3.3 (95%CI=1.3-8.5), American Society of Anesthesiologists physical status classification (ASA) with a HR of 13.5 (95%CI=1.3-136.0) and Eastern Cooperative Oncology Group (ECOG) performance status of 4, with a HR of 3.3 (95%CI=1.0-6.2)., Conclusion: Salvage PTBD with chemotherapy has the potential to achieve prolonged survival in patients with unresectable MBO, including those with failure of ERCP and/or surgical bypass., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract: Percutaneous drainage catheters (PDCs) are required for the management of benign biliary strictures refractory to first-line endoscopic treatment. While biliary patency after PDC placement exceeds 75%, long-term catheterization is occasionally necessary. In this article, we assess the outcomes of patients at our institution who required long-term PDC placement.A single-institution retrospective analysis was performed on patients who required a PDC for 10 years or longer for the management of a benign biliary stricture. The primary outcome was uncomplicated drain management without infection or complication. Drain replacement was performed every 4 to 12 weeks as an outpatient procedure.Nine patients (three males and six females; age range of 48-96 years) required a long-term PDC; eight patients required the long-term PDC for an anastomotic stricture and one for iatrogenic bile duct stenosis. A long-term PDC was required for residual stenosis or patient refusal. Drain placement ranged from 157 to 408 months. In seven patients, intrahepatic stones developed, while in one patient each, intrahepatic cholangiocarcinoma or hepatocellular carcinoma occurred.Long-term PDC has a high rate of complications; therefore, to avoid the need for using long-term placement, careful observation or early surgical interventions are required., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to examine the beneficial effects of a novel prophylactic barbiturate therapy, step-down infusion of barbiturates, using thiamylal with normothermia (NOR+sdB), on the poor outcome in the patients with severe traumatic brain injuries (sTBI), in comparison with mild hypothermia (MD-HYPO). From January 2000 to March 2019, 4133 patients with TBI were admitted to our hospital. The inclusion criteria were: a Glasgow coma scale (GCS) score of ≤8 on admission, age between 20 and 80 years, intracranial hematoma requiring surgical evacuation of the hematoma with craniotomy and/or external decompression, and patients who underwent management of body temperature and assessed their outcome at 6-12 months. Finally, 43 patients were included in the MD-HYPO (n = 29) and NOR+sdB (n = 14) groups. sdB was initiated intraoperatively or immediately after the surgical treatment. There were no significant differences in patient characteristics, including age, sex, past medical history, GCS on admission, type of intracranial hematoma, and length of hospitalization between the two groups. Although NOR+sdB could not improve the patient's poor outcome either at discharge from the intensive care unit (ICU) or at 6-12 months after admission, the treatment inhibited composite death at discharge from the ICU. The mean value of the maximum intracranial pressure (ICP) in the NOR+sdB group was <20 mmHg throughout the first 120 h. NOR+sdB prevented composite death in the ICU in patients with sTBI, and we may obtain novel insights into the beneficial role of prophylactic barbiturate therapy from suppression of the elevated ICP during the first 120 h.

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

KIT D816V mutation within exon 17 has been particularly reported as one of the poor prognostic factors in pediatric acute myeloid leukemia (AML) with RUNX1-RUNX1T1. The exact frequency and the prognostic impact of KIT D816V minor clones at diagnosis were not examined. In this study, the minor clones were examined and the prognostic significance of KIT D816V mutation in pediatric patients was investigated. Consequently, 24 KIT D816V mutations (7.2%) in 335 pediatric patients were identified, and 12 of 24 were only detected via the digital droplet polymerase chain reaction method. All 12 patients were confined in core binding factor (CBF)-AML patients. The 5 year event-free survival of the patients with KIT D816V mutation was significantly inferior to those without KIT D816V mutation (44.1% [95% confidence interval (CI), 16.0%-69.4%] vs. 74.7% [95% CI, 63.0%-83.2%] P-value = 0.02, respectively). The 5 year overall survival was not different between the two groups (92.9% [95% CI, 59.0%-NA vs. 89.7% [95% CI, 69.6%-96.8%] P-value = 0.607, respectively). In this study, KIT D816V minor clones in patients with CBF-AML were confirmed and KIT D816V was considered as a risk factor for relapse in patients with RUNX1-RUNX1T1-positive AML., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non-advanced and 301 advanced-stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide-specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8-2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4-9.9; P<0.01). 'Immune boosting' was defined when IgG levels before vaccination increased more than 2-fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive-response rates and peptide-specific IgG levels in pre- and post-vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre-vaccination factors associated with reduced clinical benefits were high c-reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post-vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre-vaccination inflammatory signatures, rather than pre- or post-vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer., (Copyright: © Uchino et al.)

Objective: Endoscopic third ventriculostomy (ETV) has now become an accepted mode of hydrocephalus treatment. However, the long-term effects of ETV for myelomeningocele-related hydrocephalus (MMC-rH) after shunt malfunction remains unclear. We aimed to assess the long-term outcome and the factors associated with the success of ETV for MMC-rH after shunt malfunction., Methods: We performed a retrospective analysis of data collected between 2001 and 2018 from 8 patients with MMC-rH after shunt malfunction, who underwent ETV at the Kurume University Hospital and were followed up for at least 5 years. We extracted data regarding age, sex, clinical symptoms, radiological imaging, intraoperative findings, and outcomes., Results: The overall success rate was 62.5% and their ETV success score is 67.5. The most frequent clinical symptom was intracranial hypertension symptoms (100 %), followed by Chiari type II symptoms (87.5 %). In preoperative MRI scans, we observed aqueduct stenosis in 6 cases, Chiari type II malformations in 7 cases, four patients had a narrow prepontine cistern, five patients had an absent septum pellucidum, and three presented with stenosis of the foramen of Monro. All cases in the failure group had the above 5 symptoms. Based on intraoperative findings, a thick third ventricle floor was found in 5 patients. Two patients had a thin hypothalamic adhesion in the third ventricle floor. They had no major complications., Conclusion: ETV for MMC-rH after shunt malfunction is an effective treatment option. However, we recommend that a neurosurgeon with extensive experience in neuroendoscopy perform ETV because MMC patients more often had intraventricular malformations than those with other hydrocephalus diseases., (Copyright © 2020. Published by Elsevier B.V.)

Objective: The optimal treatment method for persistent Blake's pouch cyst (BPC) remains unclear owing to its low prevalence. We aimed to characterize a patient population with adult BPC and to identify the risk factors associated with endoscopic third ventriculostomy (ETV) for BPC. This study reports the largest number of BPC cases in adults and is the first report to reveal the long-term outcomes of ETV in such patients., Methods: We performed a retrospective analysis of data collected from seven adult patients with BPC between 2005 and 2019. They underwent ETV at the Kurume University Hospital and were followed up for five years or more. We extracted data regarding patient age, sex, clinical symptoms, radiological imaging, intraoperative findings and outcomes., Results: The ages of the patients ranged between 30 and 60 years (45 ± 12 years). The mean postoperative follow-up time was 92.1 ± 13.5 months. The overall success rate was 71.4%. The most frequent symptom was headache (86%), followed by mild cognitive impairment (71%). The average cerebrospinal fluid pressure was slightly elevated (18.4 ± 1.4 cmH2O). A decrease in ventricular size (Evans' index) detected early after ETV was associated with satisfactory clinical outcomes (p = 0.02). The incidence of prepontine scarring was observed in all cases of the ETV failure group. A significant risk factor for ETV was the to-and-fro movements of the third ventricle floor after ETV (p = 0.048)., Conclusions: ETV could be a safe and effective treatment option for adult patients with BPC. It is important that prepontine scarring and the to-and-fro movements of the third ventricle after ETV should be confirmed carefully when performing ETV on adult patients with BPC., (Copyright © 2020. Published by Elsevier B.V.)

Background: Reactive lymphoid hyperplasia (RLH) of the liver is a benign disorder. It is usually observed in the skin, orbit, thyroid, lung, breast, or gastrointestinal tract, but rarely in the liver. Since the first report of RLH of the liver in 1981, only 75 cases have been described in the past literature. Herein, we report a case of RLH of the liver in a patient with autoimmune hepatitis (AIH), which was misdiagnosed as hepatocellular carcinoma (HCC) preoperatively and resected laparoscopically., Case Presentation: A 43-year-old Japanese woman with autoimmune hepatitis was followed up for 5 years. During her medical checkup, a hypoechoic nodule in segment 6 of the liver was detected. The nodule had been gradually increasing in size for 4 years. Abdominal ultrasound (US) revealed a round, hypoechoic nodule, 12 mm in diameter. Contrast-enhanced computed tomography (CT) demonstrated that the nodule was slightly enhanced in the arterial dominant phase, followed by perinodular enhancement in the portal and late phases. A magnetic resonance imaging (MRI) scan showed low signal intensity on the T1-weighted image (T1WI) and slightly high signal intensity on the T2-weighted image (T2WI). The findings of the Gd-EOB-DTPA-enhanced MRI were similar to those of contrast-enhanced CT. Tumor markers were all within the normal range. The preoperative diagnosis was HCC and a laparoscopic right posterior sectionectomy was performed. Pathological examination revealed that the nodular lesion was infiltrated by small lymphocytes and plasma cells, and germinal centers were present. Immunohistochemistry was positive for B cell and T cell markers, indicating polyclonality. The final diagnosis was RLH of the liver., Conclusions: The pathogenesis of RLH of the liver remains unknown, and a definitive diagnosis based on imaging findings is extremely difficult. If a small, solitary nodule is found in female patients with AIH, the possibility of RLH of the liver should be considered.

Background: Carcinoma of the ampulla of Vater with distant metastases is regarded as unresectable. Systemic chemotherapy is basically the treatment of choice for such tumors., Case Presentation: A 68-year-old woman was referred to our hospital and diagnosed with carcinoma of the ampulla of Vater with lymph node and multiple liver metastases. She underwent systemic chemotherapy with a combination of gemcitabine and cisplatin. After 19 months of treatment, the primary tumor and liver metastases were difficult to detect on follow-up images. Shrinkage of the enlarged lymph nodes was also confirmed. Surgical resection was performed with curative intent after a multidisciplinary meeting. Pathological examination of the resected specimen showed no residual tumors. Systemic chemotherapy achieved a pathological complete response. The postoperative course was uneventful, and the patient remained free of recurrent disease at 10 months of follow-up., Conclusion: This case shows the possibility of conversion surgery after systemic chemotherapy for carcinoma of the ampulla of Vater.

Background: For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized., Methods: Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated., Results: A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively)., Conclusion: cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup.

Background: Several possible mechanisms exist for the spread of a primary tumor to the leptomeninges in leptomeningeal carcinomatosis. This report describes a case caused by direct bleeding in the subarachnoid space from a neoplastic cerebral aneurysm rupture., Case Description: A 48-year-old Japanese woman, who was diagnosed with breast carcinoma (pT3 pN2 M0) at the age of 45 years and underwent mastectomy and chemotherapy, was admitted in a coma following a sudden-onset severe headache. Computed tomography revealed diffuse hemorrhage in the subarachnoid space, and angiography revealed an aneurysm at the distal middle cerebral artery. Superficial temporal artery-middle cerebral artery bypass, aneurysmal trapping, and aneurysm resection were performed within 24 hours of admission. Staining for AE1/AE3 revealed accumulation of atypical cells with a high nuclear-cytoplasmic ratio in the aneurysmal wall. After showing initial improvement, she developed disturbed consciousness due to complicated ventricular enlargement on day 45. Although the cerebrospinal fluid in the acute phase had no atypical cells, subsequent testing revealed atypical cells, which supported a diagnosis of leptomeningeal carcinomatosis due to breast cancer dissemination. The patient died on day 78 after receiving standard endocrine therapy and radiation therapy., Conclusions: Tumor cells reach the leptomeninges via hematogenous spread or direct extension from preexisting lesions and can undergo neuraxis dissemination via the cerebrospinal fluid. Subarachnoid hemorrhage and leptomeningeal carcinomatosis are both devastating conditions with extremely poor prognoses. This patient experienced delayed disturbed consciousness leptomeningeal carcinomatosis with decreased performance status, which made it difficult to justify aggressive treatment on the basis of her poor prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Microvascular invasion (MVI) is recognized as a risk factor for early recurrence of hepatocellular carcinoma (HCC) within the Milan criteria after curative treatment., Methods: One hundred eleven consecutive patients with HCC within the Milan criteria who underwent hepatic resection were retrospectively reviewed. Independent preoperative predictors of MVI were identified, and a scoring system was developed using significant predictors., Results: MVI was identified in 51 of 111 patients (46%). Multivariate analysis identified the following independent predictors of MVI: alpha-fetoprotein (AFP) of > 95 ng/mL (odds ratio [OR], 9.87; 95% confidence interval [95% CI], 2.24-56.8; P = 0.002), des-γ-carboxy prothrombin (DCP) of > 55 mAU/mL (OR, 5.50; 95% CI, 2.09-15.4; P < 0.001), tumor size of > 2.8 cm (OR, 6.10; 95% CI, 2.07-20.0; P < 0.001), and non-smooth tumor margin in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) (OR, 5.34; 95% CI, 1.84-16.9; P = 0.002). A clinical scoring system was developed using these four variables. Within a total possible score of 0 to 4, the prevalence of MVI with a score of 0, 1, 2, 3, and 4 was 4.5%, 24.0%, 45.5%, 91.7%, and 100%, respectively (P < 0.001). The area under the curve of the scoring system was 0.865 based on the receiver operating characteristic curve analysis of the prediction score., Conclusions: Our clinical scoring system, consisting of AFP, DCP, tumor size, and tumor margin in Gd-EOB-DTPA-enhanced MRI, can be valuable for predicting MVI in HCC within the Milan criteria before curative treatment.

Background: It remains unclear whether indocyanine green (ICG) angiography could reduce the rate of postoperative anastomotic leakage (AL) following rectal surgery. The aim was to determine whether intraoperative ICG angiography could decrease symptomatic AL following laparoscopic low anterior resection (LAR)., Methods: This is a retrospective study of 149 patients with rectal cancer who underwent laparoscopic LAR at a single institution. Propensity score matching (PSM) was employed to compare groups with and without ICG angiography., Results: Before PSM, the symptomatic AL rate was 10.4% (5/48) in patients with ICG angiography, compared with 6.9% (7/101) in cases without ICG angiography (P = 0.52). In patients with ICG angiography, poor perfusion of the proximal colon judged by ICG angiography led to additional colon resection in 27.1% (13/48). Symptomatic AL occurred in 30.8% (4/13) of the patients who had revision of the transection site, whereas it occurred in only 2.9% (1/35) of the patients who did not need revision of the transection site (P = 0.015). After PSM, the symptomatic AL rate was 8.8% (3/34) in patients with ICG angiography, compared with 14.7% (5/34) in cases without ICG angiography (P = 0.71). In univariate analysis, high BMI, preoperative chemotherapy, and lateral lymph node dissection were significantly associated with symptomatic AL. Multivariate analysis indicated that only lateral lymph node dissection remained significantly associated with AL (odds ratio, 10.05; 95% confidence interval, 1.75-58.61; P = 0.011)., Conclusions: Intraoperative ICG angiography is useful for prediction of AL following laparoscopic LAR.

Background: Acute subdural hematoma (ASDH) is a serious traumatic disease, and predictive methods for hematoma growth are necessary to decide whether emergent operation is necessary. This study aimed to evaluate the incidence of "leakage" using computed tomography angiography (CTA) in patients with ASDH and to identify its prognostic value., Methods: Sixty-seven patients with ASDH were examined using CTA (mean age 64.1 ± 20.6 years; 24 men) by analyzing two serial scans (CTA phase and delayed phase). We defined a positive leakage sign as a > 10% increase in Hounsfield units (HU) in the region of interest. Hematoma expansion was determined using plain CT after 24 h in patients who did not undergo emergent surgery., Results: Of the 67 patients, conservative therapy was administered to 35 patients; of these patients, 9 showed hematoma expansion, and 8 of these 9 patients (88.9%) showed positive leakage signs. The sensitivity and specificity of leakage signs to hematoma expansion in the no-surgery group were 88.8% and 76.1%, respectively. All positive leakage signs were found within 4.5 h of injury; patients showing negative leakage signs showed a decreased tendency towards hematoma 24 h after injury. Patients presenting with positive leakage signs had poor outcomes., Conclusions: The results indicated that the leakage sign is a sensitive predictor of hematoma expansion and poor outcomes in ASDH. If the hematoma is small but leakage sign-positive, strict observation is necessary and aggressive surgery may improve outcomes.