CA19-9 Reduction After 4 Months of Treatment Is a Prognostic Factor for Locally Advanced Pancreatic Cancer.

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients. PATIENTS AND METHODS: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC. RESULTS: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01). CONCLUSION: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy.

Molecular-targeted Therapy for Metastatic Renal Cell Carcinoma As First-line Therapy: A Single Institution 13-year Experience.

We aimed to identify the role of first-line monotherapy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in patients with metastatic RCC. Eligible patients were categorized into three groups (favorable, intermediate, and poor risk) according to the International Metastatic RCC Database Consortium risk criteria. Overall survival (OS) was the primary endpoint. Survival was compared using the log-rank test. A total of 108 patients were retrospectively analyzed. The numbers of patients in the favorable-, intermediate-, and poor-risk groups were 32 (30%), 66 (61%), and 10 (9%), repestively. The median OS values in the entire cohort was 36 months (95% confidence interval [CI] 29-53). The median OS in the favorable, intermediate, and poor risk groups were 94 months (95% CI: 43-Not reached), 30 months (95% CI: 20-38), and 8 months (95% CI: 0-Not reached), respectively (p<0.05). Prior nephrectomy, clear cell histology, clinical T stage ≤2, no metastasis at the time of diagnosis, nivolumab beyond first-line therapy, and objective response to VEGFR-TKIs were factors significantly prolonging OS on univariate analysis. VEGFR-TKI monotherapy as first-line therapy was an effective treatment option for patients with metastatic clear cell RCC with favorable risk.

Pancreatic cancer diagnosed by the detection of gross hematuria due to urinary bladder metastasis: A case report.

Pancreatic cancer is not easy to detect at its early stages due to difficulties in identifying symptoms at these stages. As it progresses, abdominal pain, loss of appetite, abdominal distension, jaundice and pain in the back, especially the lower back, might develop. Moreover, sudden onset or worsening of diabetes mellitus may be seen, which often prompts screening for the detection of pancreatic cancer. Since it rapidly spreads to surrounding tissues and organs, pancreatic cancer has a poor prognosis. However, metastasis to the bladder is rare, with few cases diagnosed on the basis of detecting gross hematuria. The current study presents a case of gross hematuria and exacerbated diabetes in a 90-year-old woman. Cystoscopy revealed a non-papillary tumor in the posterior bladder wall. Pathological examination of bladder tumor specimens obtained via transurethral resection revealed adenocarcinoma. Subsequent systemic examinations revealed primary pancreatic cancer that had metastasized to the bladder. To the best of our knowledge, this is the second reported case of pancreatic cancer diagnosed based on the detection of gross hematuria due to bladder metastasis, since 1992.

Population-based incidence and outcomes of acute aortic dissection in Japan.

AIMS: The population-based incidence and outcomes of acute aortic dissection (AAD) are still unknown because some patients are already dead on arrival, and the accurate diagnosis of AAD is difficult due to the low autopsy rate. We performed a population-based review of all patients with AAD in a well-defined geographical area in Japan between 2016 and 2018. METHODS AND RESULTS: Data of all patients with AAD at Miyazaki Prefectural Nobeoka Hospital (MPNH), which performs medical care for 120 000 residents, were collected retrospectively. The emergency medical service is dedicated to the transfer of all patients in this area to the MPNH. For all patients who were dead on arrival, the diagnosis of AAD was made by autopsy imaging (AI) using computed tomography. The age-adjusted incidence and mortality per 100 000 population were calculated using the Japanese population distribution model in 2015. The total incidence of AAD was 79 (type A: 64.5%, n = 51). Of those, 60.8% (31/51) of patients with type A and 21.4% (6/28) with type B were dead on arrival and diagnosed by AI. The 30-day mortality rates were 74.5% (38/51) in type A and 25.0% (7/28) in type B. The age-adjusted incidence and mortality of AAD per 100 000 inhabitants were 17.6 (type A: 11.3, type B: 6.2) and 9.9 (type A: 8.4, type B: 1.5), respectively. CONCLUSIONS: The population-based survey of AAD showed that the age-adjusted incidence of AAD was two-fold higher than in previous reports, and the actual mortality rates were markedly higher due to the high incidence of dead-on-arrival.

Impact on operative outcomes of laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases.

INTRODUCTION: The efficacy of laparoscopic simultaneous resection of primary colorectal cancer and synchronous colorectal liver metastases (SCRLM) remains unclear. METHODS: We retrospectively evaluated data from 258 patients who had undergone simultaneous curative resection of the primary tumor and SCRLM from 2006 to 2017. We compared surgical outcomes between open, hybrid (laparoscopic colorectal resection and open hepatectomy), and pure laparoscopic approaches. Surgical outcomes were also evaluated between the open hepatectomy (OH) group (ie, open/hybrid surgery) and the laparoscopic hepatectomy (LH) group (ie, pure laparoscopic surgery) in 141 patients later in the study period (2013-2017), when the clinical indications for laparoscopic hepatectomy were restricted to simple wedge resection and/or left lateral sectionectomy in our center. RESULTS: The pure laparoscopic approach was associated with significantly less intraoperative blood loss and a significantly shorter postoperative hospital stay than the open and hybrid approaches. Late in the study period, operative outcomes in the LH group (n = 37) were more favorable than for the OH group (n = 104) in terms of intraoperative blood loss and postoperative hospital stay. In patients with rectal cancer, however, earlier postoperative recovery in the LH group did not differ significantly from the OH group. CONCLUSION: Laparoscopic simultaneous resection of SCRLM with the primary tumor by simple hepatectomy is safe and may enhance patients' postoperative recovery, especially in patients with colon cancer.

Impact of structural and process quality indicators on the outcomes of acute aortic dissection.

OBJECTIVES: The mortality of acute aortic dissection (AAD) remains high, and evidence-to-practice gaps exist in real-world treatment. We explored the first quality indicators (QIs) for AAD management and evaluated the associations between the achievement of these QIs and the outcome in a nationwide administrative database. METHODS: A systematic search was performed to establish initial index items for QIs. An evaluation was performed through an expert consensus meeting using the Delphi method. We studied 18 348 patients who had AAD (type A: 10 131; type B: 8217) in the Japanese Registry of All Cardiac and Vascular Diseases database between April 2012 and May 2015. The associations between the achievement of QIs [categorized into tertiles (low, middle and high)] and in-hospital mortality were determined by multivariable mixed logistic regression analyses. RESULTS AND CONCLUSION: We developed a total of 9 QIs (5 structural and 4 process). Lower achievement rates of QIs were significantly associated with higher in-hospital mortality in both types [type A = middle: odds ratio (OR) 4.03; 95% confidence interval (CI) 3.301-4.90; P < 0.001; low: OR 15.68; 95% CI 11.67-21.06; P < 0.001 vs high; type B = middle: OR 3.48; 95% CI 2.19-5.53; P < 0.001; low: OR 7.79; 95% CI 4.65-13.06; P < 0.001 vs high]. Various sensitivity analyses showed consistent results. High achievement rates of QIs were significantly associated with reduced in-hospital mortality. Evaluating each hospital's management using QIs would help to equalize treatment quality and demonstrate the evidence-to-practice gaps in real-world treatments for AAD.

Current status of the management and outcomes of acute aortic dissection in Japan: Analyses of nationwide Japanese Registry of All Cardiac and Vascular Diseases-Diagnostic Procedure Combination data.

BACKGROUND: Despite recent advances in the diagnosis and management, the mortality of acute aortic dissection remains high. This study aims to clarify the current status of the management and outcome of acute aortic dissection in Japan. METHODS: A total of 18,348 patients with acute aortic dissection (type A: 10,131, type B: 8217) in the Japanese Registry of All Cardiac and Vascular Diseases database between April 2012-March 2015 were studied. Characteristics, clinical presentation, management, and in-hospital outcomes were analyzed. RESULTS: Seasonal onset variation (autumn- and winter-dominant) was found in both types. More than 90% of patients underwent computed tomography for primary diagnosis. The overall in-hospital mortality of types A and B was 24.3% and 4.5%, respectively. The mortality in type A patients managed surgically was significantly lower than in those not receiving surgery (11.8% (799/6788) vs 49.7% (1663/3343); p<0.001). The number of cases managed endovascularly in type B increased 2.2-fold during the period, and although not statistically significant, the mortality gradually decreased (5.2% to 4.1%, p=0.49). Type A showed significantly longer length of hospitalization (median 28 days) and more than five times higher medical costs (6.26 million Japanese yen) than those in type B. The mean Barthel index at discharge was favorable in both type A (89.0±22.6) and type B (92.6±19.0). More than two-thirds of type A patients and nearly 90% of type B patients were directly discharged home. CONCLUSIONS: This nationwide study elucidated the clinical features and outcomes in contemporary patients with acute aortic dissections in real-world clinical practice in Japan.

High incidence of recess formation at myopectineal orifice during laparoscopic surgery.

BACKGROUND: Groin hernias are frequently seen in clinical practice. The purpose of this study was to determine the rate of patients who might have latent groin hernia. METHODS: During laparoscopic abdominal surgery, we observed the area around the groin lesion and attempted to evaluate the degree of recess at myopectineal orifice. The classification defining the recess was as follows: Grade 0: no recess, Grade I: slight recess with a visible bottom, Grade II: deep recess with an invisible bottom, Grade III: other organ invaginated into the recess, and Grade IV: confirmed bulging on the body surface. RESULTS: From 2009 to 2011, 46 patients were enrolled. A recess around myopectineal orifice were detected in 20 patients. The lesions were as follows: 11 on the lateral side of the inferior epigastric artery (IEA), five on the internal side of the IEA, three at both sites and one found at the femoral ring. According to the grade classification of these groin hernias, 26 (57%) were Grade 0, 14 (30%) Grade I, 4 (9%) Grade II, 1 (2%) Grade III, and 1 (2%) Grade IV. CONCLUSIONS: This study showed that rate of patients with asymptomatic latent groin hernias is relatively high in Japanese.

Exploratory Research on Latent Esophageal Motility Disorders in Dysphagia Patients.

BACKGROUND/AIMS: High-resolution manometry (HRM) has been applied to assess esophageal motility disorders. However, the frequency and types of motility disorders in patients with dysphagia, which are frequently seen in clinical practice, are not clear. We evaluated latent esophageal motility disorders associated with dysphagia. METHODS: The study included patients without erosive esophageal mucosal damage and with dysphagia symptoms refractory to at least 8 weeks of standard-dose proton pump inhibitors. After enrolment, HRM was used to evaluate for esophageal motility disorder based on the Chicago classification. RESULTS: Esophageal motility disorder was found in 58 of 100 patients and was classified based on the causes: achalasia (13%), esophagogastric junction outflow obstruction (16%), distal esophageal spasms (3%), weak peristalsis (14%), frequently failed peristalsis (5%), and hypertensive peristalsis (7%). CONCLUSION: Primary esophageal motility disorder was found in approximately 50% of cases in dysphagia patients. Therefore, esophageal motility disorder is not an uncommon condition and should be sought for in order to elucidate precisely the cause of dysphagia.

[CLINICAL EFFICACY OF SUSTAINED HIGH-EFFICACY DAILY DIAFILTRATION USING A MEDIATOR-ADSORBING MEMBRANE AND DIRECT HEMOPERFUSION WITH A POLYMYXIN B-IMMOBILIZED FIBER COLUMN IN TREATING ACUTE EXACERBATION OF IDIOPATHIC INTERSTITIAL PNEUMONIAS].

OBJECTIVES: The aim of this study is to investigate the clinical outcomes of patients with steroid-resistant acute exacerbation of idiopathic interstitial pneumonias treated with blood purification therapy comprising direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP) and sustained high-efficacy daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA). METHODS: The clinical outcomes and respiratory function were retrospectively compared between 6 patients who underwent blood purification therapy (blood purification group) and 15 patients (control group) who blood purification therapy. RESULTS: The patients in the blood purification group showed a higher PaO2/FiO2 ratio than those in the control group. Twenty-eight days (83%; 5/6 vs. 20%; 3/15) and ninety days (67%; 4/6 vs. 6.7%; 1/15) survival rates were also higher in the blood purification group. The blood purification group also showed a better 90-day survival curve (Hazard ratio=0.260) compared to the control group. CONCLUSIONS: In conclusion, combination blood purification therapy comprising PMX-DHP and SHEDD-fA may be used to treat acute exacerbation of idiopathic interstitial pneumonias.

[Ascending aorta cannulation in stanford type a acute aortic dissection].

Establishment of cardiopulmonary bypass for Stanford type A acute aortic dissection( type A AAD) should be quick and safe. The femoral artery, axillary artery, ascending aorta, and left ventricular apex are potential access points for cannulation. The most important reason for establishing cardiopulmonary bypass for type A AAD is to allow antegrade blood flow through the true lumen. Starting in 2007, Jakob et al, and Inoue et al. applied the technique of ascending aortic cannulation for type A AAD. From 2008, we applied this method of ascending aorta cannulation in 8 patients and compared preoperative, operative, and postoperative data with a control group, or the femoral artery cannulation group. Ascending aorta cannulation was done safely and easily with the use of the Seldinger technique under epiaortic color Doppler echography and transesophageal echography. No cerebral events or hypoperfusion-based complications occurred in the group of ascending aorta cannulation. Given that no cases of complication occurred using this method, it could be considered as an effective choice of cannulation for cardiopulmonary bypass.

[A case of docetaxel-induced acute lung injury refractory to treatment].

A 59-year-old man was diagnosed with squamous cell cancer of the upper lobe of the left lung 11 months before his current admission. The clinical stage was T2N3M1(Stage IV). We started chemotherapy(carboplatin/gemcitabine), which was administered for 7 courses and discontinued 5 months before admission, but he subsequently showed a local relapse. Therefore, we restarted second-line chemotherapy(docetaxel)on admission. Only a single dose of docetaxel was administered, but the patient was diagnosed with respiratory failure 18 days afterwards. The chest roentgenogram and computed tomography showed ground-glass opacities. Bronchoalveolar lavage and blood test data showed no evidence of infection. We diagnosed the patient with acute lung injury induced by docetaxel. The patient was admitted to the intensive care unit, and therapy with steroids and sivelestat was initiated. In addition, artificial respiration, direct hemoperfusion with a polymyxin B-immobilized fiber column, etc., were performed. However, this intensive care regimen was unsuccessful, and the patient died 31 days after docetaxel administration. Docetaxel is generally used in the treatment of non-small-cell lung cancer. However, the present case showed that its use might lead to fatal drug-induced lung injury.

[Bronchial asthma-like symptoms induced by pulmonary embolism].

A 75-year-old woman who lived in a retirement home was admitted to the emergency room of our hospital because of acute respiratory failure with sudden onset of wheezing on awakening. A differential diagnosis of heart failure, showed that she had experienced an attack of bronchial asthma. She was therefore given beta-agonists via inhalation and theophylline and steroids intravenously. Her wheezing decreased but her respiratory failure persisted. Therefore, she was transferred to the intensive care unit and was referred to our department. Contrast-enhanced computed tomography of her chest showed pulmonary embolisms involving both lower lung lobes. Moreover, pulmonary perfusion scintigraphy showed defects in both lower lobes. Thus, pulmonary embolism was diagnosed. Subsequently, we started anticoagulant therapy, and her respiratory failure was saved. Pulmonary embolism is known to induce symptoms such as bronchial asthma, although such symptoms are rare.

Magnetic resonance findings of bile duct adenoma with calcification.

Computed tomographic (CT) and magnetic resonance (MR) appearances of bile duct adenoma (BDA in a patient who underwent partial hepatectomy of segment 8 are presented. BDA showed a ring-shaped hyperdense area suggesting calcification and ring enhancement on CT. It appeared hypointense on both T1- and T2-weighted MR images. Preoperatively, the diagnoses considered included metastatic carcinoma, cholangiocarcinoma, tuberculosis, and rare tumors such as epithelioid hemangioendothelioma. The radiological findings were confirmed by pathological investigation.

Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB).

Staphylococcal superantigens (SsAgs) have gained attention as one of the factors aggravating atopic dermatitis (AD) and several potential mechanisms of AD aggravation by SsAgs have been reported. Tea catechin has been found to have many unique antimicrobiological activities such as antibacterial, antiviral, antifungal and antitoxic effects. In the present study, we investigated the inhibitory effect of the green tea catechin extract, Polyphenon, and (-)-epigallocatechin gallate (EGCg) on staphylococcal enterotoxin B (SEB) and its mechanisms of action, and we also discuss the possibility of therapeutic benefits for AD patients of tea catechin. Polyphenon inhibited the lethal toxicity of SEB and the SEB-induced production of TNF-alpha, IFN-gamma and IL-4 following its intraperitoneal administration to BALB/c mice. Although Polyphenon is composed of several isomers among which EGCg is approximately 50% of the total, we considered that most of the inhibitory effect of Polyphenon in mice could be attributed to EGCg. EGCg was immediately bound to SEB molecules and neutralized SEB in a dose- and incubation time-dependent manner without molecular weight alteration of the SEB molecule. Furthermore, EGCg inhibited SEB-induced TNF-alpha and IFN- gamma production and IL-2, IFN-gamma, IL-10 and IL-12 p40 mRNA expression in human PBMCs from normal donors in a dose-dependent manner. Inhibition of SsAg-induced T-cell activation by catechin was observed in both in vivo and in vitro studies, suggesting that catechin may be useful in the treatment of AD.