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Patients diagnosed with resectable pancreatic ductal adenocarcinoma often experience early recurrence even after upfront R0 resection. This study aimed to define early recurrence and identify preoperative risk factors for early recurrence after upfront pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma of the pancreatic head.This multicenter, retrospective study involved 500 patients who underwent pancreaticoduodenectomy resectable pancreatic ductal adenocarcinoma of the pancreatic head at 10 institutions between 2007 and 2016. Preoperative, intraoperative, and postoperative clinicopathological results were compared between early and non-early recurrence groups. Predictors of early recurrence were determined using statistical analyses.Log-rank tests revealed a significant difference (P.001) between recurrence within 3 to 6 months and 6 to 9 months. Early recurrence was subsequently defined as recurrence within 6 months. Patients were categorized into early recurrence (n = 104) and non-early recurrence groups (n = 389). The median overall survival of the early and non-early recurrence groups was 8.6 months and 42.6 months (P.001), respectively. Preoperatively, high carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion, and diabetes mellitus were identified as independent predictive risk factors for early recurrence according to multivariate analysis. Comparing survival rates among patients with 3, 2, 1, or none of these factors, the median overall survival was 17.6 (n = 90), 21.2 (n = 184), 47 (n = 141), and 61.5 (n = 73) months, respectively.The optimal period that defines the early recurrence for resectable pancreatic ductal adenocarcinoma of the pancreatic head is 6 months. Tumor size ≥20 mm, preoperative carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion of the tumor, and the presence of diabetes mellitus are independently associated with early recurrence.

Phenotypic alterations in the lung epithelium have been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown because of the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 57,918 cells from lungs of patients with COPD, smokers without COPD, and never-smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. Although epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that increased in patients with COPD and specifically expressed a series of chemokines including CXCL1 and CXCL8. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.

While right ventricular (RV) involvement is commonly observed in patients with cardiac sarcoidosis (CS), the utility of strain imaging to detect RV involvement is unclear. We aimed to investigate the association between RV free wall longitudinal strain (RVFWLS) and cardiovascular events in patients with CS.We studied 51 patients with CS who were diagnosed between 2012 and 2020. All patients underwent comprehensive echocardiographic evaluation, and RVFWLS was assessed using 2-dimensional speckle tracking echocardiography. The primary outcome was major adverse cardiovascular events (MACEs).During a median follow-up duration of 548 days, 11 patients exhibited MACEs. In the univariable Cox proportional hazards model, the baseline RVFWLS was associated with MACEs (hazard ratio: 1.29, p = 0.008). The addition of RVFWLS to the conventional echocardiographic parameters exhibited a significant incremental value associated with MACEs. Patients with reduced RVFWLS showed a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging in RV wall (p = 0.02) and trends toward higher prevalence of fluorodeoxyglucose uptake in RV (p = 0.06). A serial echocardiographic evaluation revealed that patients with events showed a worsening in RVFWLS, while others showed a trend toward improvement.Impaired RVFWLS at baseline was associated with MACEs in patients with CS. RVFWLS could be an important surrogate of disease activity and prognosis by detecting active RV involvement in CS.

Balloon-assisted enteroscopy allows endoscopic treatments in the deeper segments of the small bowel. Endoscopic balloon dilation has become a popular minimally invasive alternative for the treatment of Crohn's disease-associated small intestinal strictures. As a supplement to the Clinical Practice Guidelines for Enteroscopy, the Japan Gastroenterological Endoscopy Society's Working Committee has developed the present "Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures," based on new scientific techniques and evidence. The guidelines cover standard procedures for the insertion route of the balloon endoscope, bowel preparation, indications, procedure-related complications, efficacy, target diameter and duration, management of multiple strictures, and the current state of combined and alternative treatments. Unresolved future research questions are also listed in this guideline.

Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS).Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated.In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were 1.25, 1.09, and 0.88, respectively.Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.

The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy.Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study.Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period.Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR.We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs).All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound.Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

As liquid-based cytology (LBC) specimens preserve high-quality DNA, clinical sequencing of LBC specimens using next-generation sequencing (NGS) is becoming a common strategy. This study aimed to evaluate the feasibility of NGS-based custom-made panels for evaluating MUC promoter methylation in LBC specimens.Thirty-one patients with pancreatic cancer were enrolled in the study. Cancer tissue samples were obtained using endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB). LBC, formalin-fixed paraffin-embedded (FFPE), and fresh frozen specimens were prepared for DNA extraction after pathological diagnosis. These specimens were then subjected to NGS analysis using custom-made cancer gene screening and methylation panels comprising 28 cancer-related genes and 13 gene promoter regions, including MUC1, MUC2, and MUC4.The success rate of NGS using the cancer gene panel was comparable among the LBC, FFPE, and frozen specimens, and the presence of cancer cell-derived somatic mutations in each specimen was confirmed. The specimens were then tested using a methylation panel that revealed the sequential methylation status of CpG islands located in the promoter regions of MUC genes. The methylation status results obtained from LBC specimens were almost comparable with those from FFPE and frozen specimens.MUC and other gene methylation analyses using an NGS-based panel were successfully performed in residual LBC specimens obtained by EUS-FNA/FNB. Therefore, this approach provides an alternative source of molecular tests for gene mutations and methylation, especially in the pancreatic cancers, which are often unresectable and unsuitable for obtaining FFPE specimens.

Given the increased incidence of esophageal cancer (EC) in individuals over 80 years old, the optimum therapeutic strategy for elderly patients is needed to be established with scientific evidence. Here, we studied the short-term and long-term outcomes after treatment of patients aged 80 years old or older with EC.Eighty patients with EC aged 80 years old or older, who underwent esophagectomy (n=23), definitive chemoradiotherapy (dCRT) (n=46) or best supportive care (n=11) between January 2010 and March 2019 were included in this study, and clinical data were compared among these groups.Surgery had a great benefit on the 3-year overall survival (OS) compared to dCRT (68.4% vs. 29.3%, p0.01). The cure rates of treatment were 86.9% in surgery and 34.8% in dCRT. dCRT led to a better 3-year OS compared to BSC (29.3% vs. 0%, p0.01); however, dCRT did not improved OS in patients with T4. Patients with T4 had high frequency of adverse events and treatment-related death in dCRT; CTCAE Grade 3-5 was observed in 100% of all T4 patients and Grade 5 in 57.1%. Multivariate analysis revealed that T4 was an independent risk factor of treatment-related death after dCRT (p0.01).Surgery is the first treatment option for resectable EC even in elderly patients, and dCRT can be considered as an alternative. However, dCRT may induce severe toxicity especially in T4 EC patients.

Gastrinoma may cause refractory esophageal stricture due to gastro-esophageal reflux disease (GERD), but imaging technologies have limited power in its diagnosis. A 74-year-old female with a history of peptic ulcers suffered from repeated epigastralgia, and she visited a local hospital. An esophago-gastro-duodenoscopy (EGD) demonstrated severe reflux esophagitis and multiple peptic ulcers. Blood examination revealed a high value of fasting serum gastrin. Multi-detector computed tomography showed a hypervascular and tiny nodule in duodenal bulb, although other imaging technologies did not. Short-term medication with a proton pump inhibitor or potassium-competitive acid blocker was intermittently provided, but dysphagia was repeatedly worsened, and she was referred to our division. Serum hypergastrinemia was retained, and EGD reexamination depicted esophageal stricture, treated by multiple sessions of endoscopic balloon dilatation. Primary tumor was not identified by the morphological imaging technologies, but a selective arterial secretagogue injection test suggested its existence in the duodenum or pancreatic head. Pancreaticoduodenectomy was performed, and histological study identified 2 mm-sized microgastrinoma buried in Brunner`s glands on the posterior wall of the duodenum bulb. We reported a case with difficulty in diagnosis of the smallest sporadic gastrinoma of the duodenum, which might cause refractory GERD-associated stricture.

To evaluate the predictors of a difficult Pringle maneuver (PM) in laparoscopic liver resection (LLR) and to assess alternative procedures to PM.Data from patients undergoing LLR between 2013 and 2020 were reviewed retrospectively. Univariate and multivariate analyses were performed and the outcomes of patients who underwent PM or alternative procedures were compared.Among 106 patients who underwent LLR, PM could not be performed in 18 (17.0%) because of abdominal adhesions in 14 (77.8%) and/or collateral flow around the hepatoduodenal ligament in 5 (27.8%). Multivariate analysis revealed that Child-Pugh classification B (p = 0.034) and previous liver resection (p 0.001) were independently associated with difficulty in performing PM in LLR. We evaluated pre-coagulation of liver tissue using microwave tissue coagulators, saline irrigation monopolar, clamping of the hepatoduodenal ligament using an intestinal clip, and hand-assisted laparoscopic surgery as alternatives procedures to PM. There were no significant differences in blood loss (p = 0.391) or transfusion (p = 0.518) between the PM and alternative procedures.Child-Pugh classification B and previous liver resection were identified as predictors of a difficult PM in LLR. The alternative procedures were found to be effective.

Glycoproteins produced by tumor cells are involved in cancer progression, metastasis, and the immune response, and serve as possible therapeutic targets. Considering the dismal outcomes of pancreatic ductal adenocarcinoma (PDAC) due to its unique tumor microenvironment, which is characterized by low antitumor T-cell infiltration, we hypothesized that tumor-derived glycoproteins may serve as regulating the tumor microenvironment. We used glycoproteomics with tandem mass tag labeling to investigate the culture media of three human PDAC cell lines, and attempted to identify the key secreted proteins from PDAC cells. Among the identified glycoproteins, prosaposin (PSAP) was investigated for its functional contribution to PDAC progression. PSAP is highly expressed in various PDAC cell lines; however, knockdown of intrinsic PSAP expression did not affect the proliferation and migration capacities. Based on the immunohistochemistry of resected human PDAC tissues, high PSAP expression was associated with poor prognosis in patients with PDAC. Notably, tumors with high PSAP expression showed significantly lower CD8

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.

Advances in endoscopic technology, including magnifying and image-enhanced techniques, have been attracting increasing attention for the optical characterization of colorectal lesions. These techniques are being implemented into clinical practice as cost-effective and real-time approaches. Additionally, with the recent progress in endoscopic interventions, endoscopic resection is gaining acceptance as a treatment option in patients with ulcerative colitis (UC). Therefore, accurate preoperative characterization of lesions is now required. However, lesion characterization in patients with UC may be difficult because UC is often affected by inflammation, and it may be characterized by a distinct "bottom-up" growth pattern, and even expert endoscopists have relatively little experience with such cases. In this systematic review, we assessed the current status and limitations of the use of optical characterization of lesions in patients with UC.A literature search of online databases (MEDLINE via PubMed and CENTRAL via the Cochrane Library) was performed from 1 January 2000 to 30 November 2021.The database search initially identified 748 unique articles. Finally, 25 studies were included in the systematic review: 23 focused on differentiation of neoplasia from non-neoplasia, one focused on differentiation of UC-associated neoplasia from sporadic neoplasia, and one focused on differentiation of low-grade dysplasia from high-grade dysplasia and cancer.Optical characterization of neoplasia in patients with UC, even using advanced endoscopic technology, is still challenging and several issues remain to be addressed. We believe that the information revealed in this review will encourage researchers to commit to the improvement of optical diagnostics for UC-associated lesions.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials.Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry.The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 μmBy revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

Minimally invasive esophagectomy (MIE) has been widely accepted as a treatment for esophageal cancer. This retrospective study compared the short-term outcomes and surgical invasiveness between thoracoscopic esophagectomy (TE) and mediastinoscopic esophagectomy with pneumomediastinum (pneumatic mediastinoscopic esophagectomy [PME]).A total of 72 patients who underwent TE or PME were included and assessed for their surgical findings, postoperative complications, and inflammatory responses on postoperative day (POD) 1, 3, 5, and 7.The PME group exhibited a significantly shorter operative time and fewer lymph nodes retrieved than the TE group. Furthermore, the PME group tended to have greater incidences of recurrent laryngeal nerve palsy and lower incidences of atelectasis than the TE group. The PME group had significantly lower white blood cell counts on POD 5, serum C-reactive protein (CRP) levels on POD 3 than the TE group.PME seems to be less invasive than TE and can be considered the preferred option for patients with lower-stage esophageal cancer expected to have severe pleural adhesion or who cannot tolerate TE.

Purpose To investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Methods A total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery. Results Thirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC. Conclusions Our scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.

Lymphatic metastasis is a major route of metastasis in distal cholangiocarcinoma (DCC). The present study aimed to elucidate the pattern of lymph node (LN) metastasis and the effectiveness of LN dissection and postoperative adjuvant chemotherapy in patients with DCC.Patients who underwent surgical resection with curative intent for DCC were enrolled. The nomenclature of the LN stations was defined according to the Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines. Effectiveness of LN dissection of each station was calculated using frequency of LN metastasis to the station and 5-year survival rate of patients with LN metastasis to that station.Of the 105 patients included in the study, 46 (43.8%) had LN metastasis, and 43 (41.0%) underwent postoperative adjuvant therapy. LN metastasis, serum carbohydrate antigen (CA) 19-9 level 37 U/mL, and positive bile duct margin were independent risk factors for shorter overall survival (OS). The most common metastatic LN station at surgery was No. 13 (32.7%), followed by No. 12 (19.2%), No. 17 (9.6%), and No. 8 (6.6%). There was no effectiveness of LN dissection of the station No. 8, 14, and 16. Adjuvant chemotherapy was significantly associated with longer OS in patients with LN metastasis but not in those with positive ductal margins or serum CA 19-9 level 37 U/mL.Postoperative adjuvant chemotherapy was associated with a better prognosis in patients with DCC and LN metastasis. However, a more effective therapeutic strategy is required to improve the prognosis of patients with other negative prognostic factors.

To evaluate the right colic vascularity, focusing on the confluences of veins.The subjects of this retrospective study were 100 patients who underwent laparoscopic extended right hemicolectomy (Lap-ERHC) between April 2015 and September 2020, at our hospitals. Veins draining into the superior mesenteric vein (SMV) included the ileocecal vein (ICV), the right colic vein (RCV), the middle colic vein (MCV), and the gastrocolic trunk of Henle (GCT). Veins draining into vessels other than the SMV were defined as accessory colic veins (aICV, aRCV or aMCV).The GCT, aRCV, and aMCV were found in 86, 89, and 15 patients, respectively. In 66 patients with one aRCV, drainage was split as the anterior superior pancreaticoduodenal vein (ASPDV) in 12, the right gastroepiploic vein (RGEV) in 7, and the GCT in 47. In 23 patients with two aRCVs, drainage was split as the ASPDV in 4, the RGEV in 1, the GCT in 11, and the ASPDV and GCT in 7. In 14 patients with one aMCV, drainage was split as the GCT in 8, the splenic vein in 5, and the first jejunal vein (FJV) in 1. One patient had two aMCVs, draining into the GCT and the FJV.The findings of our evaluation of vascular anatomy, focusing on confluences of the colic veins, provides useful information for colorectal surgeons.

Whether organ-preserving pancreatic surgery has an advantage in postoperative short- and long-term outcomes or not is still unknown because only small case series studies have been available to date. In this multicenter retrospective study, we aimed to elucidate the clinical advantage and disadvantage of organ-preserving pancreatectomy among patients with low-grade malignant pancreatic tumors and benign pancreatic diseases.We included patients diagnosed with benign or low-malignant pancreatic tumor who underwent pancreaticoduodenectomy (PD) in 621 cases, duodenum-preserving pancreatic head resection (DPPHR) in 31 cases, middle pancreatectomy (MP) in 148 cases, distal pancreatectomy (DP) in 814 cases, and spleen-preserving distal pancreatectomy (SPDP) in 259 cases between January 1, 2013, and December 31, 2017. Preoperative backgrounds, surgical outcomes and pre- and postoperative (3, 6, 12, 24, and 36 months) nutritional status were compared between these procedures.In terms of short-term outcomes, the incidence of pancreatic fistula in patients who underwent MP was significantly higher than in patients with standard pancreatectomy. As for the long-term pancreatic functions in the cases of head or body lesion, both exocrine and endocrine functions after MP were significantly favorable compared with the PD group from 3 to 36 months after surgery. In pancreatic body or tail lesion, significant advantage of endocrine function, but not exocrine function, was found in the MP group compared to standard DP at all time points.MP may contribute to the improvement of postoperative quality of life for patients with pancreatic body low-malignant tumors, rather than PD or DP; however, reducing the incidence of short-term complications such as pancreatic fistula is a future challenge.

The litter size of mouse strains is determined by the number of oocytes naturally ovulated. Many attempts have been made to increase litter sizes by conventional superovulation regimens (e.g., using equine or human gonadotropins, eCG/hCG but had limited success because of unexpected decreases in the numbers of embryos surviving to term. Here, we examined whether rat-derived anti-inhibin monoclonal antibodies (AIMAs) could be used for this purpose. When C57BL/6 female mice were treated with an AIMA and mated, the number of healthy offspring per mouse increased by 1.4-fold (11.9 vs. 8.6 in controls). By contrast, treatment with eCG/hCG or anti-inhibin serum resulted in fewer offspring than in nontreated controls. The overall efficiency of production based on all females treated (including nonpregnant ones) was improved 2.4 times with AIMA compared with nontreated controls. The AIMA treatment was also effective in ICR mice, increasing the litter size from 15.3 to 21.2 pups. We then applied this technique to an in vivo genome-editing method (improved genome-editing via oviductal nucleic acid delivery, i-GONAD) to produce C57BL/6 mice deficient for tyrosinase. The mean litter size following i-GONAD increased from 4.8 to 7.3 after the AIMA treatment and genetic modifications were confirmed in 80/88 (91%) of the offspring. Thus, AIMA treatment is a promising method for increasing the litter size of mice and may be applied for the easy proliferation of mouse colonies as well as in vivo genetic manipulation, especially when the mouse strains are sensitive to handling.

The effect of hepatic steatosis on the development of colorectal liver metastases (CRLM) remains unknown. This study evaluated the usefulness of fat signal fraction assessed with magnetic resonance imaging (MRI) and the effect of hepatic steatosis on hepatic recurrences following initial hepatectomy for CRLM.Between January 2013 and December 2019, 64 patients underwent initial hepatectomy for CRLM. The medical records of these patients were reviewed to evaluate the recurrence and survival outcomes.The fat signal fraction was positively correlated with the nonalcoholic fatty liver disease activity score and liver-spleen ratio. Recurrence following the initial hepatectomy was observed in 48/64 patients, and hepatic recurrence was observed in 30/64 patients. The fat signal fraction was significantly higher in patients with hepatic recurrence after initial hepatectomy. The hepatic recurrence rate was 69.2% in patients with fat signal fraction ≥ 0.0258, which was significantly higher than that in patients with fat signal fraction 0.0258. Hepatic recurrence-free survival rate was significantly higher in patients with fat signal fraction 0.0258 than in those with fat signal fraction ≥ 0.0258. Multivariate analyses revealed that fat signal fraction ≥ 0.0258 was an independent risk factor for hepatic recurrence.The fat signal fraction assessed with MRI was significantly associated with hepatic recurrence following initial hepatectomy for CRLM.

Left-ventricular (LV) global longitudinal strain (GLS) has been reported to be a robust and sensitive marker of chemotherapy-induced cardiac damage. Image quality is paramount for accurate GLS measurements. In real-world cardio-oncology settings, the incidence of suboptimal echocardiography quality and its significance in clinical decision-making have not been well investigated. This prospective study examined the incidence and impact of suboptimal echocardiographic image quality on detecting subtle myocardial damage by chemotherapy.Seventy-seven consecutive patients with breast cancer (age, 52 ± 12 years, 76 women, 33 with left-sided breast cancer) were included in this study. Echocardiography was performed at 3-month intervals 1 year before and after chemotherapy initiation. We classified the image quality of each echocardiographic acquisition into three groups: optimal, suboptimal, or inadequate for speckle tracking.Among the 376 examinations obtained during the cardiac monitoring, the image quality in 194 (52%) was optimal, suboptimal in 159 (42%), and inadequate in 23 (6%). The interobserver reproducibility was 0.91 in the optimal and 0.21 in the suboptimal group. In contrast, the optimal group showed progressive impairment in both GLS (p = 0.001) and LV ejection fraction (LVEF) (p 0.001) during follow-up, and the suboptimal group showed a progressive decrease in LVEF (p = 0.006), but not in GLS (p = 0.13). Left-sided mammotomy and/or reconstruction surgery and high body mass index were significant determinants of suboptimal image quality.Even in cases of minor image quality impairment, the physician should assess GLS carefully to avoid errors in crucial clinical decision-making.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn’s disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

and purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).Of 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).The current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.

Although gemcitabine-based chemotherapy is the standard of care for advanced biliary tract cancers (BTCs), adjuvant phase III studies (BCAT in Japan, PRODIGE 12 in France) failed to show benefit, possibly owing to fewer patients (n = 225 and n = 194) compared with the adjuvant capecitabine BILCAP trial (n = 447). We performed a combined analysis of both gemcitabine-based chemotherapy adjuvant studies.We performed individual patient data meta-analysis of all patients included in BCAT and PRODIGE 12. BCAT study randomised patients with extrahepatic cholangiocarcinoma to single-agent gemcitabine or observation. PRODIGE 12 randomised patients with all BTC subtypes to gemcitabine-oxaliplatin combination or observation. Combined analysis was performed using Kaplan-Meier curves and a Cox regression model stratified on the trial.Two hundred and twelve versus 207 patients were randomised in the gemcitabine-based chemotherapy versus observation arms. Baseline characteristics were balanced between arms. The median follow-up was 5.5 years. After 258 relapse-free survival (RFS) events, there was no difference in RFS (log-rank p = 0.45; hazard ratio [HR] = 0.91 [95% confidence interval [CI] 0.71-1.16]; p = 0.46). RFS rates at five years were 40.8% (95%CI: 33.9%-47.5%) for gemcitabine-based chemotherapy versus 36.6% (95%CI: 29.8%-43.4%) for observation. After 201 deaths, there was no difference in overall survival (OS) (log-rank p = 0.83; HR = 1.03 [95%CI: 0.78-1.35]; p = 0.85). OS rates at five years were 50.5% (95%CI: 43.1%-57.4%) for gemcitabine-based chemotherapy versus 49.3% (95%CI: 41.6%-56.5%) for observation.With 419 patients included, this analysis did not show significant improvement in RFS and no trend in improvement in OS. Gemcitabine-based chemotherapy should not be used as an adjuvant treatment for BTC.

International audience; AIMS: To evaluate the current management and survival of patients with left-sided infective endocarditis (IE) complicated by congestive heart failure (CHF) in the ESC-EORP European Endocarditis (EURO-ENDO) registry. METHODS AND RESULTS: Among the 3116 patients enrolled in this prospective registry, 2449 (mean age: 60 years, 69% male) with left-sided (native or prosthetic) IE were included in this study. Patients with CHF (n~=~698, 28.5%) were older, with more comorbidity and more severe valvular damage (mitro-aortic involvement, vegetations >10\,mm and severe regurgitation/new prosthesis dehiscence) than those without CHF (all p\,≤q\,0.019). Patients with CHF experienced higher 30-day and 1-year mortality than those without (20.5% vs. 9.0% and 36.1% vs. 19.3%, respectively) and CHF remained strongly associated with 30-day (odds ratio[OR] 2.37, 95% confidence interval [CI] [1.73-3.24; p\,10\,mm, severe valvular regurgitation and/or new prosthetic dehiscence, perivalvular complication, and prosthetic IE (OR 0.22, 95% CI 0.12-0.38; p\

Objectives This study aimed to develop reliable biomarkers that improve the ability of bile cytology to diagnose cholangiocarcinoma vs benign biliary lesions. Methods Many studies indicate that microRNAs (miRNAs) are potential candidates for the early diagnosis of cancer. We analyzed the expression of five tumor-associated miRNAs (miR-31-5p, miR-122-5p, miR-378d, miR-182-5p, and miR-92a-3p) in cytology samples using quantitative reverse transcription polymerase chain reaction. We collected 52 surgically resected tissue samples, 84 cytologic specimens from smears (53 cases of cancer and 31 cases of noncancer), and 40 residual sediments after smearing for routine cytology at Hiroshima University Hospital. Results The expression of miR-31-5p, miR-378d, and miR-122-5p was significantly higher in cancer tissues than those in normal tissues, while miR-182-5p expression was lower. The expression of miR-31-5p, miR-378d, miR-182-5p, and miR-92a-3p was significantly higher in detached cell samples from smears of cholangiocarcinoma cases than in those from noncancer cases. Conclusions These results suggest that the analysis of miRNAs in bile cytologic specimens is a promising auxiliary tool for distinguishing cholangiocarcinoma from benign biliary lesions.

Extensive distal pancreatectomy (ExDP) can transect the pancreatic parenchyma more from the right side than conventional distal pancreatectomy (CDP) can. This study aimed to evaluate the short- and long-term outcomes of ExDP for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic body, located adjacent to the portal vein (PV).Medical records of 98 patients who underwent ExDP (n = 15) or CDP (n = 83) for PDAC were retrospectively reviewed. Short- and long-term outcomes of the two groups were compared. Propensity score matched analysis was additionally performed to minimize the impact of treatment allocation bias.In the total cohort, the CDP group had a significantly higher proportion of pancreatic tail lesions (P 0.01), higher proportion of males, and larger tumor size. Of the 15 patients who underwent ExDP, 11 could be matched. These differences of patients' characteristics were not observed after matching. Before and after matching, the duration of surgery, blood loss, rate of morbidity including pancreatic fistula, and postoperative course were comparable between the groups. The rate of recurrence and recurrence pattern were also not significantly different between the groups. ExDP for PDAC of the pancreatic body near the PV did not increase local or lymph node recurrence. The disease-free and overall survival did not differ between the groups.Surgical and oncological outcomes after ExDP for PDAC were acceptable and comparable to those after CDP. ExDP is a feasible procedure, and could be an option for the treatment of PDAC of the pancreatic body near PV.

Despite having once been extensively used for cosmetics or pain reduction, the use of single-incision laparoscopic cholecystectomy (SILC) has declined in recent years due to technical difficulties and a reported increase in complications. Since the introduction of SILC in 2009, our hospital has been actively involved with this technique. Our experience suggests that SILC is not a difficult procedure and can be safe and useful, with particularly excellent cosmetic outcomes. This study retrospectively details the outcomes of SILC at our hospital.Data on 1469 cases of SILC performed on a waitlist basis at Osaka Police Hospital from May 2009 to December 2020 were collected and retrospectively analysed.The median operative time and blood loss were 96 min and 0 mL, respectively. A total of 46 patients (3.1%) required conversion surgery, including 36 needing additional ports and 10 requiring laparotomy. Intraoperative complications included common bile duct injury in 1 patient (0.07%) and right hepatic artery injury in 1 patient (0.07%), with no other organ injury. Postoperative Clavien-Dindo 3 or higher complications were observed in 18 patients (1.2%). Incisional hernias occurred in 15 patients (1.0%). The median postoperative hospital stay was 3 days.This study showed that SILC can be performed safely without any increase in complications, as reported previously. Granted that it is performed safely, SILC may be a useful technique due to its superior cosmetic outcomes or pain reduction.

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

BackgroundCreating a box lesion in the posterior wall of the left atrium from the epicardial side of the beating heart remains a challenge. Although a transmural lesion can be created by applying radiofrequency (RF) energy at clampable sites, there is still no reliable energy source to use to create a roof and bottom linear lesion to connect bilateral pulmonary vein (PV) cuff lesions produced with RF energy, because the inner blood flow in the unclampable free wall weakens the thermal effect on the outside. Our aim was to apply the newly developed infrared coagulator to create linear transmural lesions on the beating heart thoracoscopically to treat atrial fibrillation (AF).Case presentationA 71-year-old male was referred to our hospital with a diagnosis of hypertrophic cardiomyopathy and permanent atrial fibrillation. The patient was first diagnosed with atrial fibrillation 20 years before. Direct current cardioversion had been performed every few years a total of four times, but sinus rhythm restoration had always been temporary. The patient wanted to be free from anticoagulant therapy, symptom of palpitations, and fear of possibility of cerebral infarction. Transthoracic echography revealed no valvular dysfunction. Cardiac scintigraphy showed no evidence of myocardial ischemia. The electrocardiogram indicated AF with a 0.2 mV of f-wave amplitude. On February 27, 2020, thoracoscopic PV isolation together with infrared roof- and bottom-line ablation to create a box lesion and left atrial appendage amputation (LAAA) were performed. The coagulator could be applied to clinical thoracoscopic surgery to successfully create a box lesion without any complication. The patient restored a regular sinus rhythm, it has been maintained for eleven months, and there have been no adverse events. ConclusionsThe infrared coagulator might have enough potential to create transmural lesions on the beating heart in thoracoscopic AF surgery.

BACKGROUND/PURPOSE This study aimed to prospectively assess the current prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) after total pancreatectomy (TP). METHODS Between August 2015 and December 2017, we prospectively collected data from 68 Japanese centers on 148 consecutive patients who underwent TP whose computed tomography (CT) attenuation values were evaluated for 12 months. We defined post-TP NAFLD as a liver parenchyma CT value of less than 40 Hounsfield units (HU). Data on perioperative variables were retrieved from all patients and evaluated using univariate and multivariate analyses to identify the perioperative risk factors of NAFLD. RESULTS In this prospective cohort study, supplementation of pancreatic exocrine enzymes was provided to all 148 patients, and 97% of them were treated with high-titer pancrelipase (median dosage: 1800 mg) postoperatively. Indeed, 29 patients (19.6%) developed NAFLD within a year after TP. Multivariate analysis revealed that female sex (p=0.002), higher body mass index (BMI) (p=0.001), and postoperative diarrhea (p=0.038) were independent risk factors for post-TP NAFLD. However, post-TP NAFLD ameliorated in 11 patients (37.9%) at 12 months after surgery. CONCLUSIONS Among patients with risk factors such as female sex, higher BMI, and postoperative diarrhea, attention should be paid to the occurrence of NAFLD after TP.

Objectives Complete endoscopic healing, defined as Mayo endoscopic score (MES)=0, is an optimal target in the treatment of ulcerative colitis (UC). However, some patients with MES=0 show clinical relapse within 12 months. Histologic goblet mucin depletion has emerged as a predictor of clinical relapse in patients with MES=0. We observed goblet depletion in vivo using an endocytoscope, and analyzed the association between goblet appearance and future prognosis in UC patients. Methods In this retrospective cohort study, all enrolled UC patients had MES=0 and confirmed clinical remission between October 2016 and March 2020. We classified the patients into two groups according to the goblet appearance status: preserved-goblet and depleted-goblet groups. We followed the patients until March 2021 and evaluated the difference in cumulative clinical relapse rates between the two groups. Results We identified 125 patients with MES=0 as the study subjects. Five patients were subsequently excluded. Thus, we analyzed the data for 120 patients, of whom 39 were classified as the preserved-goblet group and 81 as the depleted-goblet group. The patients were followed-up for a median of 549 days. During follow-up, the depleted-goblet group had a significantly higher cumulative clinical relapse rate than the preserved-goblet group (19% [15/81] vs. 5% [2/39], respectively; P=0.02). Conclusions Observing goblet appearance in vivo allowed us to better predict the future prognosis of UC patients with MES=0. This approach may assist clinicians with onsite decision-making regarding treatment interventions without a biopsy.

BACKGROUND Left atrial (LA) global strain has been studied as an early marker of LA dysfunction, followed by LA dilatation. Recently, a novel dedicated software for LA 3-dimensional speckle tracking echocardiography (LA-3DSTE) has allowed us to assess anatomy-based six-segmental LA deformation. This study aimed to assess the accuracy of LA-3DSTE software in measuring LA volume and to reveal the characteristics of regional LA reservoir strain. METHODS Fifty patients with paroxysmal atrial fibrillation who underwent computed tomography (CT) and 3D-STE were enrolled. The LA volumes obtained by 3D-STE and CT were compared, and regional LA strain was analyzed. Six LA segments (anterior, septal, inferior, lateral, roof, and posterior) were determined on the basis of LA anatomy. RESULTS In 50 patients (mean age, 64 years; 62% male), the 3D-STE-derived LA volume index (LAVI) showed good correlation with the CT-derived index, (r = 0.78, p < 0.001) with an underestimate bias of 10.5 ± 11.0 ml/m2 (p < 0.001). The lateral LA strain was negatively correlated with LAVI and emptying fraction, while the anterior and septal strains were not. In the 1st quantile LA volume group, the segmental LA strain was heterogeneous, that is, the lateral and inferior strains were greater than the anterior strain. While in the 3rd quantile LA volume group, the lateral and inferior strains were decreased, and there was no regional difference. CONCLUSION LA volume obtained by 3D-STE and CT showed a good correlation. LA segmental analysis by 3D-STE enables early identification of how LA dysfunction affects lateral and inferior LA strains, consistent with anatomical features.

Brain or B-type natriuretic peptide (BNP) is an objective marker to diagnose the presence of heart failure (HF) and assess its severity. However, the determinants of serum BNP level in elderly patients with severe aortic valve stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) have not been well investigated.We prospectively studied 106 AS patients who underwent TAVI. Cardiac catheterization, transesophageal echocardiography, and blood collection for plasma BNP level measurements were performed simultaneously just before the TAVI procedures.Ninety-nine patients (83.9±5.0 years, 33% male) were studied. The natural logarithm of BNP (lnBNP) level was 5.4±0.9 pg/mL. Significant correlations with lnBNP level were observed in: 1) the history of syncope, prior HF medication, and New York Heart Association class III or IV (R=0.255, p=0.011) (R=0.210, p=0.037) (R=0.402, p0.001), 2) albumin and hemoglobin level (R=-0.289, p=0.004) (R=0.263, p=0.009), 3) Left ventricular (LV) ejection fraction and global longitudinal strain (LVGLS) (R=-0.338, p0.001) (R=0.447, p0.001), 4) LV end-diastolic volume index (EDVI), LV mass index, and left atrial volume index (R=0.280, p=0.005) (R=0.366, p0.001) (R=0.337, p0.001), 5) the catheter-measured pressure gradient across the aortic valve (AVPG) (R=0.365, p0.001). Note that LV wall stress was not significantly correlated with lnBNP level. LVGLS, AVPG, hemoglobin level, and LVEDVI were independently correlated with ln BNP level (R=0.652, LVGLS; β=0.395, p0.006, AVPG; β=0.291, p=0.001, hemoglobin level; β=-0.216, p=0.011, and LVEDVI; β=0.203, p=0.016, respectively).In severe AS patients candidate for TAVI, multiple factors, including the severities of AS and HF conditions and subclinical LV dysfunction determined by LVGLS affects plasma BNP level.

Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.5-4.4 years. It was significantly effective in two patients and did not cause serious side effects in any patient. Vedolizumab might be effective and safe for pediatric GI-aGVHD refractory to other treatments, but this must be confirmed in future studies.

A 53-year-old woman was diagnosed with lymphoplasmacytic lymphoma (LPL)/Waldenström's macroglobulinemia (WM) in 2008. Six courses of R-COP (rituximab, cyclophosphamide, vincristine, and prednisolone) resulted in complete remission, but LPL/WM relapsed in 2015. After six courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), the M-peak disappeared, but the patient presented with muscle weakness and sensory disturbance in the lower extremities. No lesions were apparent in the brain parenchyma, but T2-weighted magnetic resonance imaging (MRI) showed a signal-hyperintense area with contrast enhancement in the spinal cord at the C2-4 and Th2-3 levels, and cerebrospinal fluid (CSF) examination showed only a few mononuclear cells. In 2020, the patient started to require walking assistance, and MRI findings worsened. Neurologically, lower limb muscle strength was reduced (manual muscle test score 3), and sensations of touch and pain were about 30% of normal. Vibratory sensation was absent at the knees and medial malleoli, accompanied by dysuria due to neurogenic bladder. CSF cell count was 15/μl (all mononuclear cells). Bing-Neel syndrome (BNS) was diagnosed and tirabrutinib was started. Within 2 months of treatment, lower extremity muscle strength had normalized and MRI findings had improved. Tirabrutinib may offer a promising therapeutic option for BNS.

Background: Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson’s disease (PD) patients, but its effectiveness is not well understood. Objective: This systematic review and meta-analysis aimed to assess the evidence regarding the effectiveness of long-term physiotherapy to improve motor symptoms and reduce antiparkinsonian medication dose in PD patients. Methods: Pubmed, Cochrane, PEDro, and CINAHL were searched for randomized controlled trials before August 31, 2020 that investigated the effectiveness of physiotherapy for 6 months or longer on motor symptoms and levodopa-equivalent dose (LED) in PD patients with Hoehn and Yahr stage 1– 3. We performed random effects meta-analyses for long-term physiotherapy versus no/control intervention and estimated standard mean differences with 95% confidence intervals (CIs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation approach. Results: From 2,940 studies, 10 studies involving 663 PD patients were assessed. Long-term physiotherapy had favorable effects on motor symptoms in off medication state [– 0.65, 95% CI – 1.04 to – 0.26, p = 0.001] and LED [– 0.49, 95% CI – 0.89 to – 0.09, p = 0.02]. Subgroup analyses demonstrated favorable effects on motor symptoms in off medication state by aerobic exercise [– 0.42, 95% CI – 0.64 to – 0.20, p

'Monitoring of immune responses following mogamulizumab-containing treatment in patients with adult T-cell leukaemia-lymphoma (ATL)' (MIMOGA) is a multicentre prospective clinical study (UMIN000008696). In the MIMOGA study, we found that a lower percentage of CD2- CD19+ B cells in peripheral blood mononuclear cells (PBMC) was a significant unfavourable prognostic factor for overall survival (OS). Accordingly, we then analysed the immunoglobulin G (IgG) heavy-chain repertoire in PBMC by high-throughput sequencing. Of the 101 patients enrolled in the MIMOGA study, for 81 a sufficient amount of PBMC RNA was available for repertoire sequencing analysis. Peripheral IgG B cells in patients with ATL had a restricted repertoire relative to those in healthy individuals. There was a significant positive correlation between the Shannon-Weaver diversity index (SWDI) for the IgG repertoire and proportions of B cells in the PBMC of the patients. Multivariate analysis identified two variables significantly affecting OS: a higher serum soluble interleukin-2 receptor level, and a lower SWDI for the IgG repertoire [hazard ratio, 2·124; 95% confidence interval, 1·114-4·049; n = 44]. The present study documents the importance of humoral immune responses in patients receiving mogamulizumab-containing treatment. Further investigation of strategies to enhance humoral immune responses in patients with ATL is warranted.

Esophageal bronchogenic cysts are rare, and since a limited number of cases has been reported, the treatment plan for asymptomatic patients is difficult. A 55-year-old man without any symptoms visited our hospital for further examination of an esophageal mass detected on simple computed tomography. Upper endoscopy showed the protruding, submucosal mass covered by normal mucosa, and endoscopic sonography confirmed hypoechoic lesions originating from the muscularis propria. The patient was diagnosed as having an esophageal duplication cyst and underwent thoracoscopic resection. Pathological findings were consistent with an esophageal bronchogenic cyst. The patient was discharged without any problems on the 6th postoperative day. Upper endoscopy was performed 6 months after surgery, and no evidence of esophageal diverticula or narrowing was present. In conclusion, early thoracoscopic resection of esophageal bronchogenic cysts, before appearance of the symptom, can be a considerable treatment option because it is less invasive and may be advantageous for obtaining a definitive diagnosis in patients who are candidates for safe surgical resection.

Recent advances in the CRISPR/Cas9 system have demonstrated it to be an efficient gene-editing technology for various organisms. Laboratory mice and rats are widely used as common models of human diseases; however, the current standard method to create genome-engineered animals is laborious and involves three major steps: isolation of zygotes from females, ex vivo micromanipulation of zygotes, and implantation into pseudopregnant females. To circumvent this, we recently developed a novel method named Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). This method does not require the ex vivo handling of embryos; instead, it can execute gene editing with just one step, via the delivery of a genome-editing mixture into embryos in the oviduct, by electroporation. Here, we present a further improvement of GONAD that is easily applicable to both mice and rats. It is a rapid, low-cost, and ethical approach fulfilling the 3R principles of animal experimentation: Reduction, Replacement, and Refinement. This method has been reconstructed and renamed as "improved GONAD (i-GONAD)" for mice, and "rat improved GONAD (rGONAD)" for rats.

In this study, we analyzed prognostic radiological tools and surgical outcomes for radiologically pure solid adenocarcinomas (AD) and squamous cell carcinoma (SQ) in clinical stage IA. We retrospectively investigated 130 patients who underwent surgical resections. We assessed the predictive risk factors for recurrence and pathological lymph node metastasis (LNM). There was no statistical difference in recurrence free survival (RFS) or cancer-specific survival (CSS) between AD and SQ groups (p = 0.642 and p = 0.403, respectively). In the whole cohort, tumor size on lung window and mediastinal settings, and tumor disappearance ratio using high-resolution computed tomography (HRCT) were not prognostic parameters (p = 0.127, 0.066, and 0.082, respectively). The maximal standardized uptake value (SUVmax) using positron emission tomography-CT was associated with recurrence (p = 0.016). According to the receiver operating characteristic curve, the cut-off value of SUVmax for recurrence was 4.6 (p = 0.016). The quantitative continuous variables using any radiological tools were not associated with LNM. However, tumor diameter on mediastinal setting ≥8 mm with SUVmax ≥2.4 could be a risk factor for LNM. Pure solid AD and SQ were equivalent for the RFS and CSS. SUVmax was useful to predict recurrence. The tumor diameter on a mediastinal setting and SUVmax were useful in predicting pathological LNM.