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Esophagectomy and pancreatectomy are recognized as highly invasive procedures with relatively high complication rates; therefore, careful indication decisions are required. The depth of tumors invading adjacent organs, such as the aorta, vertebral body, and trachea, is defined as T4, and are estimated to have a low survival rate even after treatment. Conversely, pancreatic invasion of esophageal cancer is uncommon and not clearly defined as T4. Thus, it is often difficult to decide on a treatment strategy for locally advanced esophageal cancer. In this study, we describe three cases of esophagectomy with combined resection of the pancreas and spleen for esophageal cancer or esophagogastric junction cancer with invasion of the pancreatic body or tail. To the best of our knowledge, this is the first report of esophagectomy and combined resection of the pancreas and spleen in multiple patients from a single institution.

Background Although the resuscitation guidelines consider mechanical chest compressions acceptable for cardiopulmonary resuscitation (CPR) in unstable settings, the efficacy of automated chest compression devices for out-of-hospital cardiac arrest (OHCA) patients according to treatment time period remains unclear. We assessed the effectiveness of automated chest compression devices depending on time of admission based on frequency of iatrogenic chest injuries, duration of in-hospital resuscitation efforts, and clinical outcomes among OHCA patients. Methods We conducted a retrospective historical control study of OHCA patients in Japan between April 1, 2015 and March 31, 2022. Patients were divided according to time of admission; wherein day- and night-time were considered as duration between 07:00–22:59 and 23:00–06:59, respectively. These patients were then divided into two categories based on in-hospital cardiopulmonary resuscitation (IHCPR) device used: manual chest compression (mCC) group and automatic chest compression devices (ACCD) group. Univariate and multivariate ordered logistic regression models adjusted for pre-hospital confounders were used to evaluate the impact of ACCD use during IHCPR on outcomes [IHCPR duration, CPR-related chest injuries, and clinical outcomes] in day- and night-time groups. Results A total of 1,101 patients with OHCA (day-time, 809; night-time, 292) formed our study population. Of these, 215 (26.6%) and 104 (35.6%) patients underwent ACCD during IHCPR in day-and night-time groups. Multivariate model showed significant association of ACCD use with outcomes of in-hospital resuscitation, including higher rates of return of spontaneous circulation, lower incidence of CPR-related chest injuries, longer in-hospital resuscitation duration, survival to Emergency Department and hospital discharge, and survival with good neurological outcome to hospital discharge, only in the night-time group. Conclusions Patients who underwent ACCD during in-hospital resuscitation at night had a significantly longer duration of in-hospital resuscitation, lower incidence of CPR-related chest injuries, and better outcomes.

Although the out-of-hospital cardiac arrest (OHCA) survival rate has improved due to the spread of cardiopulmonary resuscitation (CPR) techniques and insights, OHCA remains a major public health issue worldwide [...]

Few studies have investigated the relationship between blood type and trauma outcomes according to the type of injury. We conducted a retrospective multicenter observational study in twelve emergency hospitals in Japan. Patients with isolated severe abdominal injury (abbreviated injury scale for the abdomen ≥ 3 and that for other organs p p = 0.012). Furthermore, type O was associated with significantly higher cause-specific mortalities, fewer VFD, and larger transfusion volumes. Blood type O was associated with significantly higher mortality and larger transfusion volumes in patients with isolated severe abdominal trauma.

Esophageal gastrointestinal stromal tumors (GISTs) are very rare, accounting for 2–5% of all GISTs. As with other GISTs, the principle of surgical treatment is complete resection with negative margins. In addition to biological grades of GISTs itselves, local recurrence due to capsular damage is a known risk. We describe two cases of massive esophageal GISTs that were successfully resected thoracoscopically after 2 months administration of 400 mg imatinib, with some discussion of the literature. Case 1, the patient was a 51-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtMtAeG, 110 × 95 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 11 months postoperatively. Case 2, the patient was a 70-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtAeG, 90 × 52 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 9 months postoperatively.

Radiogenomics has attracted attention for predicting the molecular biological characteristics of tumors from clinical images, which are originally a collection of numerical values, such as computed tomography (CT) scans. A prediction model using genetic information is constructed using thousands of image features extracted and calculated from these numerical values. In the present study, RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) tissues from 12 patients was performed to identify genes useful in evaluating clinical pathology, and 107 PDAC samples were immunostained to verify the obtained findings. In addition, radiogenomics analysis of gene expression was performed by machine learning using CT images and constructed prediction models. Bioinformatics analysis of RNA sequencing data identified integrin αV (ITGAV) as being important for clinicopathological factors, such as metastasis and prognosis, and the results of sequencing and immunostaining demonstrated a significant correlation (r=0.625, P=0.039). Notably, the ITGAV high‑expression group was associated with a significantly worse prognosis (P=0.005) and recurrence rate (P=0.003) compared with the low‑expression group. The ITGAV prediction model showed some detectability (AUC=0.697), and the predicted ITGAV high‑expression group was also associated with a worse prognosis (P=0.048). In conclusion, radiogenomics predicted the expression of ITGAV in pancreatic cancer, as well as the prognosis.

Background: Idarucizumab is the first specific reversal agent for direct oral anticoagulants. There are only a few reports of the use of idarucizumab. Case presentation: A 67-year-old man was transported to our hospital complaining of lower abdominal discomfort and dyspnea. His medical history included hypertension and atrial fibrillation treated with dabigatran. Upon arrival, he was alert, with pale skin, and cold sweats with hemodynamic instability. The imaging evaluation revealed a 79-mm abdominal aortic aneurysm and retroperitoneal hematoma. He was diagnosed with a ruptured abdominal aortic aneurysm. We immediately administered 5 g of idarucizumab for the reversal of dabigatran anticoagulation, and emergency open repair of the abdominal aortic aneurysm was performed. Normal intraoperative hemostasis was ultimately achieved. He was finally discharged without any neurological deficit, but left hip disarticulation was needed because of left limb ischemia. Conclusion: Although idarucizumab would prove useful for patients with a bleeding tendency due to taking dabigatran, it may promote thrombotic events and further studies to clarify the ideal timing for restarting anticoagulation after the administration of idarucizumab are needed.

Background Radiogenomics is an emerging field that integrates “Radiomics” and “Genomics”. In the current study, we aimed to predict the genetic information of pancreatic tumours in a simple, inexpensive, and non-invasive manner, using cancer imaging analysis and radiogenomics. We focused on p53 mutations, which are highly implicated in pancreatic ductal adenocarcinoma (PDAC), and PD-L1, a biomarker for immune checkpoint inhibitor-based therapies. Methods Overall, 107 patients diagnosed with PDAC were retrospectively examined. The relationship between p53 mutations as well as PD-L1 abnormal expression and clinicopathological factors was investigated using immunohistochemistry. Imaging features (IFs) were extracted from CT scans and were used to create prediction models of p53 and PD-L1 status. Results We found that p53 and PD-L1 are significant independent prognostic factors (P = 0.008, 0.013, respectively). The area under the curve for p53 and PD-L1 predictive models was 0.795 and 0.683, respectively. Radiogenomics-predicted p53 mutations were significantly associated with poor prognosis (P = 0.015), whereas the predicted abnormal expression of PD-L1 was not significant (P = 0.096). Conclusions Radiogenomics could predict p53 mutations and in turn the prognosis of PDAC patients. Hence, prediction of genetic information using radiogenomic analysis may aid in the development of precision medicine.

Pancreatic cancer is an aggressive tumor associated with poor survival, and early detection is important to improve patient outcomes. In the present study, we examined MIR1246 expression as a biomarker of pancreatic cancer. Total RNA was extracted from serum, urine and saliva samples from healthy subjects (n = 30) and patients with pancreatic cancer (n = 41, stage 0–IV). The MIR1246 level in each fluid was analyzed by quantitative reverse transcription-polymerase chain reaction. Significantly higher MIR1246 expression in serum and urine was observed in patients with cancer than in healthy controls. A significant positive correlation was found between serum and urine MIR1246 expression (r = 0.34). Receiver operating characteristic curves were constructed for MIR1246 in all three body fluids. The area under the curve for serum MIR1246 was 0.87 (sensitivity, 92.3%; specificity, 73.3%), and that for urine MIR1246 was 0.90 (sensitivity, 90.2%; specificity, 83.3%). With a cut-off of the control group’s mean plus twice the standard deviation, the sensitivities of MIR1246 in serum and urine for pancreatic cancer were 60.9 and 58.5%, respectively. Combining both serum and urine MIR1246 expression yielded a sensitivity of 85%. These results indicate that MIR246 may be a useful diagnostic biomarker for pancreatic cancer.

Although several reports recommend the use of systemic anticoagulation therapy in patients with severe coronavirus disease 2019 (COVID-19) pneumonia, appropriate target population and timing of administration are unknown. We assessed association between therapeutic anticoagulation administration with unfractionated heparin and outcomes in patients with severe COVID-19 pneumonia, assuming that anticoagulant administration effects are influenced by therapy timing.This retrospective observational study included severe COVID-19 patients requiring mechanical ventilation in a tertiary emergency critical care hospital intensive care unit (ICU) in Japan from May 1, 2020 to September 30, 2021. All included patients were divided into early and late-phase administration groups based on therapeutic anticoagulant administration timing (≤5 and5 days, respectively, after commencing oxygen therapy). Primary outcomes (in-hospital mortality and adverse events related to anticoagulation therapy) and secondary outcomes [veno-venous extracorporeal membrane oxygenation (ECMO), ventilator-free days (VFD), and ICU-free days] were compared between groups using univariate and multivariate models.Of 198 included patients 104 (52.5%) and 94 (47.5%) were in early-phase and late-phase administration groups, respectively. Although background characteristics were similar between the groups, the early-phase administration group had a significantly lower in-hospital mortality rate (3.8% vs. 27.7%; p0.001), lower adverse event rates (1.9% vs. 12.8%; p0.001), significantly longer VFD and ICU-free days, and lower ECMO rates, than the late-phase administration group, in the multivariate model.Late administration of therapeutic-dose anticoagulation in patients with severe COVID-19 pneumonia was significantly associated with worse outcomes than early administration.

Background Anomalous bifurcation of the right superior pulmonary vein is an important anomaly that should be recognized not only in respiratory and cardiac surgeries, but also in esophageal surgery for the safe performance of surgery. We report a case in which thoracoscopic esophagectomy was safely performed using preoperative three-dimensional computed tomography (3D CT) imaging. Case presentation An 81-year-old male patient received an upper gastrointestinal endoscopy, which revealed a 20-cm incisor at the entrance, 43-cm EGJ, and 30-mm large type 1 + IIc lesion between the 23-cm and 26-cm incisors; biopsy showed squamous cell carcinoma (SCC). Contrast-enhanced CT showed wall thickening in the anterior wall of the upper thoracic esophagus, without evidence of multi-organ invasion or lymph node metastasis. In addition, a break in the right pulmonary vein passing dorsal to the right main bronchus and flowing directly into the left atrium was observed, and 3D CT was performed preoperatively to confirm the 3D positioning. Positron emission tomography (PET)–CT showed a high degree of accumulation (SUVmax 19.95) in the upper thoracic esophagus. The patient was diagnosed with upper thoracic esophageal cancer, cT2N0M0 cStage II, and underwent thoracoscopic subtotal esophagectomy (three-region dissection) and gastric tube reconstruction. The dorsal inflow of the pulmonary vein in the right main bronchus, which was recognized on preoperative CT, was confirmed and preserved. The pathological diagnosis was basaloid squamous cell carcinoma, pT1b(SM1)N0(0/58)M0 pStage I. The postoperative course was uneventful, and the patient was discharged on postoperative day 20. Conclusions The anomalous bifurcation of the pulmonary vein in the right upper lobe area required attention because of its potential to cause massive bleeding and difficulty in securing the operative field if misidentified and damaged during surgery. Although it is not frequently encountered, it is the bifurcation anomaly that esophageal surgeons must bear in mind due to its severe consequences. Preoperative image-reading and intraoperative manipulation of this vessel are imperative for surgical safety.

Background The esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient’s prognosis. Methods Patients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated. Results A total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy. Conclusions In this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy. Trial registration This was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

BACKGROUND Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. AIM We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. METHODS The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. RESULTS The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p

The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1–14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. UMIN ID: 000,005,732, date of registration: June 7, 2011. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695

Background Although there are many studies on primary esophageal adenocarcinoma arising from Barrett's esophagus or ectopic gastric mucosa, reports on adenocarcinoma arising from esophageal cardiac glands are extremely rare. Herein, we report a case of mid-thoracic cancer antigen 19-9 (CA 19-9)-producing primary esophageal adenocarcinoma, which presumably originated from the cardiac glands. Case presentation A 74-year-old man was referred to our department with advanced esophageal cancer, which initially presented with dyspepsia. Serum levels of cancer antigen 19-9 (CA 19-9) were elevated (724.89 U/ml). Upper gastrointestinal endoscopy revealed a type 2 tumor on the posterior wall of the mid-thoracic esophagus approximately 29–32 cm from the incisor. Mucosal biopsy was consistent with a diagnosis of adenocarcinoma. Contrast-enhanced computed tomography showed a circumferential wall thickening in the mid-thoracic esophagus without enlarged lymph nodes or distant metastasis. Positron emission tomography–computed tomography showed accumulation in the primary tumor, but no evidence of lymph node or distant metastasis. According to these findings, the adenocarcinoma was staged as cT3N0M0, thereby, requiring subtotal esophagectomy with lymph node dissection. Postoperative course was uneventful. Histopathologic analysis revealed a 50 × 40 mm moderately differentiated adenocarcinoma with invasion to the thoracic duct and lymph node metastasis at #108(1/4), #109R(1/3), and #109L(1/3). After surgery, the stage was revised to moderately differentiated pT4apN2pM0 (pStage III). Immunostaining revealed expression of CA19-9 and suggested esophageal cardiac gland origin of the tumor. Three months after the surgery, the patient showed no recurrence and is undergoing outpatient observation. Conclusions We experienced a case of mid-thoracic CA19-9-producing primary esophageal adenocarcinoma, which was presumed to have originated in the esophageal cardiac glands. Due to the scarcity of studies regarding this condition, specific management needs to be further clarified.

Whether lactate clearance (LC) influences outcomes differently depending on the infection site in sepsis cases is not fully elucidated. Herein, we analyzed LC’s clinical utility as a predictor of patient outcomes according to infection site. This retrospective study, conducted at two tertiary emergency critical care medical centers in Japan, included patients with sepsis or septic shock. The associations between infection site (lungs vs. other organs) and in-hospital mortality and ventilator-free days (VFDs) were evaluated using univariable and multivariate analyses. We assessed LC’s ability to predict in-hospital mortality using the area under the receiver operating characteristic curve. Among 369 patients with sepsis, infection sites were as follows: lungs, 186 (50.4%); urinary tract, 45 (12.2%); abdomen, 102 (27.6%); and other, 36 (9.8%). Patients were divided into a pneumonia group or non-pneumonia group depending on their infection site. The pneumonia group displayed a higher in-hospital mortality than the non-pneumonia group (24.2% vs. 15.8%, p = 0.051). In the multivariate analysis, lower LC was associated with higher in-hospital mortality [adjusted odds ratio (AOR), 0.97; 95% confidence interval (CI) 0.96–0.98; p p value (AD), − 1.23; 95% CI − 2.42 to − 0.09; p = 0.025] in the non-pneumonia group. Conversely, LC did not affect in-hospital mortality (AOR 0.99; 95% CI 0.99–1.00; p = 0.134) and VFD (AD − 0.08; 95% CI − 2.06 to 1.91; p = 0.854) in the pneumonia group. Given the differences in the impact of LC on outcomes between the pneumonia and non-pneumonia groups, this study suggests that optimal treatment strategies might improve outcomes. Further studies are warranted to validate our results and develop optimal therapeutic strategies for sepsis patients.

Indocyanine green (ICG) fluorescence imaging has been used to assess the blood perfusion of the gastrointestinal tract in surgery. Especially, it was used to determine the best anastomotic site. However, in previous studies, ICG fluorescence was judged subjectively based on the visual appearance. This study evaluated the usefulness of our novel method to quantitatively assess the blood perfusion of the gastric conduit in esophagectomy based on ICG fluorescence.Twenty patients who underwent esophagectomy with gastric conduit reconstruction were prospectively investigated. Using a camera in contact with the surface of the stomach, ICG images were quantitatively evaluated using "ROIs", a software program that quantified the fluorescence intensity and created a time-fluorescence intensity curve to assess the blood perfusion three times intraoperatively.No postoperative esophago-gastrostomy leakage developed. However, after preparing the gastric conduit and just before anastomosis, the maximum increase in fluorescence intensity (FImax) significantly decreased (48.8 ± 26.0 and 31.5 ± 14.9 versus 84.9 ± 28.2; P 0.001 and P 0.001, respectively), and the time to reach FImax was significantly extended (60 ± 35.4 and 58.3 ± 34.9 versus 18.9 ± 6.5; P 0.001 and P 0.002, respectively), in comparison to the control value. Just before anastomosis, 18 cases (90%) showed an identical pattern characterized by an obtuse and low arterial inflow peak and a slow rise of fluorescence intensity over time, indicating a decreased blood flow.The quantitative analysis of ICG fluorescence imaging could objectively prove a decrease in blood perfusion-which could not be determined macroscopically-in the gastric conduit before esophageal reconstruction. The results from the present and further studies may indicate its clinical value.

Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120.We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis.The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively.The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody.The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.

Background: In the first-line treatment of metastatic colorectal cancer (mCRC) patients with CAPOX plus bevacizumab, the optimal duration of maintenance treatment without oxaliplatin to avoid discontinuation of therapy due to peripheral sensory neuropathy (PSN) remains unknown. The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned oxaliplatin intermittent strategy in mCRC.Methods: Patients with untreated mCRC were administered CAPOX [oxaliplatin 130 mg/m2 and capecitabine (2000 mg/m2 daily) as intermittent treatment for 14 days, followed by a 7-day treatment-free interval, every 3 weeks] + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety.Results: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. The relative dose intensity and the cumulative dose of oxaliplatin during the overall treatment period were 649.1 mg/m2 and 1132.5 mg, respectively. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, PSN, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%.Conclusion: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.Trial registration: This trial was registered with the University Hospital Medical Information Network on 7 June 2011 (UMIN ID: 000005732).

Objective This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in borderline resectable pancreatic cancer (BRPC). Summary background data Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. Methods A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a one-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. Results Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. Conclusions S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. Trial registration UMIN000009172.

Background Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC. Methods Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group. Results There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was − 10.0% [− 31.7–20.4%]. Conclusions Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT. Trial registration UMIN-CTR, UMIN000009172. Registered 23 October 2012

Background Although age and trauma-induced coagulopathy (TIC) are well-known predictors of poor outcome after traumatic brain injury (TBI), the interaction effect of these two predictors remains unclear.Objectives We assessed age-related differences in the impact of TIC on the outcome following isolated TBI.Methods We conducted a retrospective observational study in two tertiary emergency critical care medical centers in Japan from 2013 to 2018. A total of 1036 patients with isolated TBI [head abbreviated injury scale (AIS) ≥3, and other AIS

The p16 gene, which is also known as CDKN2A, INK4A, or CDK4I, and its products that are known to be cell cycle inhibitors and tumor suppressors have been reported to be altered in various human tumor types. Altered p16 has been indicated to be correlated with negative p16 expression using immunohistochemistry (IHC). However, its association with the prognosis remains controversial because the findings of previous studies are inconsistent. The current study evaluated the relationship between the expression levels of p16 and the clinicopathological features associated with prognosis in patients with primary pancreatic ductal adenocarcinomas (PDACs). From January 2013 to December 2017, tissues of 103 PDAC patients who had undergone elective pancreatic resection were obtained and assessed for p16 expression by IHC. No correlation was observed between p16 status and clinicopathological factors (P>0.05). Notably, negative p16 expression on IHC was not significantly associated with poor prognosis using the Kaplan-Meier method.

Background Recent studies have implicated the differences in the ABO blood system as a potential risk for various diseases, including hemostatic disorders and hemorrhage. In this study, we evaluated the impact of the difference in the ABO blood type on mortality in patients with severe trauma. Methods A retrospective observational study was conducted in two tertiary emergency critical care medical centers in Japan. Patients with trauma with an Injury Severity Score (ISS) > 15 were included. The association between the different blood types (type O versus other blood types) and the outcomes of all-cause mortality, cause-specific mortalities (exsanguination, traumatic brain injury, and others), ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate competing-risk regression models. Moreover, the impact of blood type O on the outcomes was assessed using regression coefficients in the multivariate analysis adjusted for age, ISS, and the Revised Trauma Score (RTS). Results A total of 901 patients were included in this study. The study population was divided based on the ABO blood type: type O, 284 (32%); type A, 285 (32%); type B, 209 (23%); and type AB, 123 (13%). Blood type O was associated with high mortality (28% in patients with blood type O versus 11% in patients with other blood types; p

ObjectivesThe aim of this study was to assess the risk of cardiopulmonary resuscitation (CPR) performed in out-of-hospital settings for chest injuries in patients with out-of-hospital cardiac arrest (OHCA).MethodsThis retrospective, observational study was conducted in an emergency critical care medical center in Japan. Non-traumatic OHCA patients transferred to the hospital from April 2013 through August 2016 were analyzed. The outcome was defined by chest injuries related to CPR, which is composite of rib fractures, sternal fractures, and pneumothoraces. A multivariate logistic regression analysis was performed to assess the independent risk factors for chest injuries related to CPR. The threshold of out-of-hospital CPR duration that increased risk of chest injuries was also assessed.ResultsA total of 472 patients were identified, of whom 233 patients sustained chest injuries. The multivariate logistic regression model showed that the independent risk factors for chest injuries were age and out-of-hospital CPR duration (age: AOR=1.06 [95% CI, 1.04 to 1.07]; out-of-hospital CPR duration: AOR=1.03 [95% CI, 1.01 to 1.05]). In-hospital CPR duration was not an independent risk factor for chest injuries. When the duration of out-of-hospital CPR extended over 15 minutes, the likelihood of chest injuries increased; however, this association was not statistically significant.ConclusionsLong duration of out-of-hospital CPR was an independent risk factor for chest injuries, possibly due to the difficulty of maintaining adequate quality of CPR. Further investigations to assess the efficacy of alternative CPR devices are expected in cases requiring long transportation times.TakayamaW, KoguchiH, EndoA, OtomoY. The association between cardiopulmonary resuscitation in out-of-hospital settings and chest injuries: a retrospective observational study. Prehosp Disaster Med. 2018;33(2):171–175.

The prognosis of metastatic recurrent non-small cell lung cancer (NSCLC) is poor, and chemotherapy improves survival by only a few months. The concept of oligo-recurrence, defined as a small number of new lesions at a distant site theoretically curable by local therapy, has recently been proposed for several cancers. To evaluate the possible benefits of surgical resection for oligo-recurrence, we report the outcomes of seven patients who underwent hepatic resection for oligo-recurrence of NSCLC in the liver. Among the 2038 patients who underwent resection for NSCLC between January 1997 and December 2015 at the Department of Chest Surgery, Chiba Cancer Center, 7 (0.34%) with oligo-recurrence in the liver underwent hepatectomy. Perioperative data were retrospectively reviewed, including recurrence-free and overall survival. Primary tumor histopathological types included five cases of squamous cell carcinoma, one case of adenocarcinoma, and one case of large-cell carcinoma. All patients underwent complete tumor resection without complication. The median survival duration following hepatectomy was 24.0 (range 15.2–30.2) months. Four patients were alive at the end of follow-up (23.4–30.2 months), whereas three died between 15.2 and 24.5 months. There was no evidence of second recurrence in two patients. Hepatectomy may be equally effective as multidisciplinary therapy for oligo-recurrence of NSCLC in the liver.

Impalement brain injury is rare, and the initial management of this condition is not well-established. We present a case of a well-managed brain injury caused by impalement with a metal bar. A 29-year-old man whose head had been impaled by a metal bar was transferred to our hospital. Upon arrival, he was agitated, with an unsteady gait and prominent odor of alcohol on his breath. He exhibited normal vital signs and neurological findings, except for his level of consciousness. To address the risk of secondary brain injury caused by movement of the foreign body, we immediately administered a sedative agent and muscle relaxant after the initial neurological evaluation. The imaging evaluation revealed the insertion of a metal bar into the right frontal lobe at a depth of >100 mm through the frontal bone; however, there was no apparent major vessel injury-related complication. Three hours after arrival at the hospital, a craniotomy was performed to remove the foreign body. The patient’s postoperative course was uneventful, and he was discharged after rehabilitation without any neurological deficits. The strategy of immediate immobilization to prevent the secondary brain injury is important in the initial management of a patient who has survived an impalement brain injury and presented to an emergency department.

Background Although patients with out-of-hospital cardiac arrest (OHCA) have a lower survival rate during night-time than during day-time, the cause of this difference remains unclear. We aimed to assess CPR parameters according to time period based on in-hospital cardiopulmonary resuscitation (IHCPR) duration and the frequency of iatrogenic chest injuries among OHCA patients. Methods This two-centre observational cohort study evaluated non-traumatic OHCA patients who were transferred between 2013–2016. These patients were categorised according to whether they received day-time treatment (07:00–22:59) or night-time treatment (23:00–06:59). Differences in IHCPR duration, CPR-related chest injuries, return of spontaneous circulation, and survivals to emergency department and hospital discharge were compared using a generalised estimating equation model adjusted for pre-hospital confounders. Sensitivity analysis was also performed using a propensity score matching method. Results Among 1254 patients (day-time: 948, night-time: 306), the night-time patients had a significantly shorter IHCPR duration (27.8 min vs. 23.6 min, adjusted difference: −5.1 min, 95% confidence interval [CI]: −6.7, −3.4), a higher incidence of chest injuries (40.4% vs. 67.0%, adjusted odds ratio [AOR]: 1.27, 95% CI: 1.20, 1.35), and a lower rate of return of spontaneous circulation (38.4% vs. 26.5%, AOR: 0.93, 95% CI: 0.88, 0.98). No significant differences were observed in the rates of survival to emergency department and hospital discharge. The propensity score-matched analysis revealed similar results. Conclusions Patients who underwent night-time treatment for OHCA had an increased risk of CPR-related chest injuries despite their shorter resuscitation duration. Further studies are needed to clarify the underlying mechanism(s).

We report a case of locally advanced rectal cancer invading toward sacrum treated by laparoscopic low anterior resection. A man in his 60's was diagnosed with rectal cancer expanding near to sacrum. The circumferential resection margin was assessed to be scarce. After preoperative chemotherapy, we performed laparoscopic low anterior resection. In order to obtain surgical margin, we had to cut into presacral venous plexus. With prepared sufficient devices, hemostasis was safely acquired. Pathological findings revealed clear surgical margin. It is important to prepare appropriate hemostasis devices in managing cases with high risks of intraoperative hemorrhage. Laparoscopic approach may contribute to these cases, making hemostasis easier than laparotomy with the magnified view, pneumoperitoneum and Trendelenburg position.