Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy ...remain poorly defined.
A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR).
Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P < 0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P = 0.093 and P =0.472 respectively).
In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.
Quantifying the risks and benefits of revascularization for chronic limb-threatening ischaemia (CLTI) is important. The aim of this study was to create a risk prediction model for treatment outcomes ...30 days after revascularization in patients with CLTI.
Consecutive patients with CLTI who had undergone revascularization between 2013 and 2016 were collected from the JAPAN Critical Limb Ischemia Database (JCLIMB). The cohort was divided into a development and a validation cohort. In the development cohort, multivariable risk models were constructed to predict major amputation and/or death and major adverse limb events using least absolute shrinkage and selection operator logistic regression. This developed model was applied to the validation cohort and its performance was evaluated using c-statistic and calibration plots.
Some 2906 patients were included in the analysis. The major amputation and/or mortality rate within 30 days of arterial reconstruction was 5.0 per cent (144 of 2906), and strong predictors were abnormal white blood cell count, emergency procedure, congestive heart failure, body temperature of 38°C or above, and hemodialysis. Conversely, moderate, low or no risk in the Geriatric Nutritional Risk Index (GNRI) and ambulatory status were associated with improved results. The c-statistic value was 0.82 with high prediction accuracy. The rate of major adverse limb events was 6.4 per cent (185 of 2906), and strong predictors were abnormal white blood cell count and body temperature of 38°C or above. Moderate, low or no risk in the GNRI, and age greater than 84 years were associated with improved results. The c-statistic value was 0.79, with high prediction accuracy.
This risk prediction model can help in deciding on the treatment strategy in patients with CLTI and serve as an index for evaluating the quality of each medical facility.
We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.
Records of more ...than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.
pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.
We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.
Background
Previous studies have reported that patients undergoing oesophagectomy in high‐volume hospitals experience lower mortality rates. However, there has been ongoing discussion regarding the ...validity of evidence for this association. The purpose of this study was to investigate the relationship between hospital volume and risk‐adjusted mortality following oesophagectomy in Japan, using a nationwide web‐based database.
Methods
The study included patients registered in the database as having undergone oesophagectomy with reconstruction between 2011 and 2013. Outcome measures were 30‐day and operative mortality rates. Logistic regression analysis was used to adjust for hospital volume, surgeon volume and risk factors for mortality after oesophagectomy.
Results
A total of 16 556 oesophagectomies at 988 hospitals were included; the overall unadjusted 30‐day and operative mortality rates were 1·1 and 3·0 per cent respectively. The unadjusted operative mortality rate in hospitals performing fewer than ten procedures per year (5·1 per cent) was more than three times higher than that in hospitals conducting 30 or more procedures annually (1·5 per cent). Multivariable models indicated that hospital volume had a significant effect on 30‐day (odds ratio 0·88 per 10‐patient increase; P = 0·012) and operative (odds ratio 0·86 per 10‐patient increase; P < 0·001) mortality.
Conclusion
In Japan, high‐volume hospitals had lower risk‐adjusted 30‐day and operative mortality rates following oesophagectomy compared with low‐volume hospitals.
Volume outcome effect evident in Japan
On March 28, the Japanese government decided on the “Basic Policies for Novel Coronavirus Disease Control” and called on the public to thoroughly implement social distancing measures (i.e., ...behavioral restrictions to limit the frequency and intensity of human contact), especially telework.
We used population-level questionnaire data from a social networking service (SNS), with 275,560 respondents from March 5 to April 6, to evaluate the relationship between telework implementation and the presence of a fever (body temperature higher than 37.5 °C) within 1 month as a surrogate indicator of COVID-19 infection, by occupation type and age-group.
Among company employees, statistical significance was identified in the 15- to 29-year and 30- to 59-year age-groups, showing higher fever rates in the non-teleworker group (for the 15- to 29-year age-group, non-teleworkers: 7.64%; teleworkers: 6.45%; P = 0.02; for the 30- to 59-year age-group, non-teleworkers: 3.46%; teleworkers: 3.14%; P = 0.02).
Telework remains a controversial topic in Japan as the government called for emergency measures. Although caution is warranted in interpreting our findings because our data are limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.
•Slow progress in the introduction of telework as a coronavirus disease 2019 (COVID-19) measure in Japan.•Analysis using COVID-19 monitoring responses from over 270,000 social networking service users in Japan.•Statistical relationship between teleworking and fever among company employees.•The urgent need for social support in the implementation of telework in Japan.
Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and ...preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.
This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal ...squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC.
Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35mg/m2, cisplatin 70mg/m2 i.v. on day 1, fluorouracil 700mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70mg/m2, cisplatin 70mg/m2 i.v. on day 1, fluorouracil 700mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat.
Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P=0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33–0.83, P=0.0057) and 78.6% versus 65.4% (P=0.08), respectively.
Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC.
University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear.
We evaluated MRP2 ...expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines.
MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP.
Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.
Abstract Background The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but ...few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. Methods Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. Results Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p<0.001 and p=0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p=0.04 and p<0.001, respectively), but only the regression index predicted NACRT efficacy (p=0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p<0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p=0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp2.086, p=0.043). Conclusion The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.
Background
Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total ...pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications.
Methods
Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato‐Biliary‐Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien–Dindo grade III needing reoperation, or grade IV–V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c‐statistics and a calibration plot.
Results
A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30‐day and in‐hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c‐statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81).
Conclusion
The risk model may be used to predict severe complications after total pancreatectomy.
Antecedentes
La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves.
Métodos
Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato‐Bilio‐Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien‐Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración.
Resultados
Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59‐0,81).
Conclusión
El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.
This study assessed the clinical outcomes of total pancreatectomy using a nationwide registry in Japan, and proposed a risk model for severe postoperative complications. Rates of mortality and severe complication after total pancreatectomy were lower in this study than in previous reports. The risk model showed good calibration.
Tool for preoperative risk estimation