Middle-preserving pancreatectomy with reversed pancreaticogastrostomy: report of a case

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.     

Trained innate lymphoid cells in allergic diseases

Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing T_H2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memory-like type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed.     

Rationale and Design of the Multicenter Trial on Japan Working Group on the Effects of Angiotensin Receptor Blockers Selection (Azilsartan vs. Candesartan) on Diastolic Function in the Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE Trial

Background

Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial.

Methods

The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e’) assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study.

Conclusions

The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.

     

A cholangiocellular carcinoma radically resected by central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct

A case of cholangiocellular carcinoma, involving the hepatic hilus, radically resected by central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct is presented. Preoperative surgical planning was carried out on the basis of an evaluation of the findings of ultrasonography, computed tomography, angiography, percutaneous transhepatic portography, and tube cholangiography. The operation lasted for 16 h and 15 min, with 5700 g blood loss. Postoperative recovery was very good and the patient has now been well for 26 months after surgery. Although the surgical technique of central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct is very difficult, this procedure should be indicated for selected cases of cholangiocellular carcinoma involving the hepatic hilus.     

Contribution of lung fibroblast migration in the fibrotic process of airway remodeling in asthma.

BACKGROUND: The fibrotic process in airway remodeling of asthma may be characterized by an exaggerated deposition of extracellular matrix (ECM) components such as fibronectin and type I, III and IV collagen. In the present study, we established airway remodeling model mice and examined the mechanism of fibrotic change by measuring chemotactic activity of lung fibroblasts and quantifying collagen content in lung tissues. METHODS: Airway remodeling model mice were made by ovalbumin (OA) sensitization and inhalation. Bronchoalveolar lavage (BAL) and bronchial biopsy were performed. Cell migration was assessed by the Boyden's chamber technique. The collagen content of lung tissue was measured using ELISA. RESULTS: The chemotactic activity in lung fibroblasts toward the mouse BAL fluid (BALF) was significantly increased in OA-inhaled mice. Total soluble collagen content was significantly increased in OA-inhaled mice. We observed markedly increased collagen deposition around the airway wall in OA-inhaled mice, which was not shown in saline-inhaled mice. Furthermore, fibronectin in the BALF of OA-inhaled mice was significantly higher than that in the control mice. CONCLUSIONS: The total soluble collagen content increased during the fibrotic change of airway remodeling in asthma. Furthermore, migration of fibroblasts may play a key role in this remodeling process, and fibronectin and type I and IV collagen seem to be chemotactic factors for the fibroblasts.     

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis

Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers. The common missense mutations in the TP53 gene disrupt the ability of p53 to bind to DNA and consequently to transactivate downstream genes. However, it is still not fully understood how a large number of the remaining mutations affect p53 structure and function. Here, we used a comprehensive site-directed mutagenesis technique and a yeast-based functional assay to construct, express, and evaluate 2,314 p53 mutants representing all possible amino acid substitutions caused by a point mutation throughout the protein (5.9 substitutions per residue), and correlated p53 function with structure- and tumor-derived mutations. This high-resolution mutation analysis allows evaluation of previous predictions and hypotheses through interrelation of function, structure and mutation.     

Impact of aging on the clinical outcomes of Japanese patients with coronary artery disease after percutaneous coronary intervention

Japan has become an aging society, resulting in an increased prevalence of coronary artery disease. However, clinical outcomes of elderly Japanese patients after percutaneous coronary intervention (PCI) remain unclear. Of the 15,227 patients in the Shinken Database, a single-hospital-based cohort of new patients, 1,214 patients who underwent PCI, was evaluated to determine the differences in clinical outcomes between the elderly (≥75 years) (n = 260) and the non-elderly (<75 years) (n = 954) patients. A major adverse cardiac event (MACE) was defined as a composite end point, including all-cause death, myocardial infarction (MI), and target lesion revascularization. Male gender and obesity were less common, and the estimated glomerular filtration rate (eGFR) was significantly lower in the elderly than in the non-elderly. Left ventricular ejection fraction (LVEF) was comparable between these groups. Left main trunk disease and multivessel disease were more common in the elderly than in the non-elderly group. Occurrence of MACE was frequent, and the incidences of all-cause death, cardiac death, and the admission rate for heart failure were significantly higher in the elderly patients. Multivariate analysis showed that prior MI, low eGFR, and poor LVEF were independent predictors for all-cause death in the elderly patients. Elderly patients had worse clinical outcomes than the non-elderly patients. Low eGFR and LVEF were independent predictors of all-cause death after PCI, suggesting that left ventricular dysfunction and renal dysfunction might synergistically contribute to the adverse clinical outcomes of the elderly patients undergoing PCI.     

Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy for the prediction of left ventricular reverse remodeling and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy

Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging performed at baseline are both used to evaluate the extent of myocardial fibrosis. However, no study has directly compared the effectiveness of these diagnostic tools in the prediction of left ventricular reverse remodeling (LVRR) and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients with newly diagnosed IDCM who were undergoing optimal therapy were assessed at baseline using LGE-CMR imaging and EMB; the former measured LGE area and the latter measured collagen volume fraction (CVF) as possible predictive indices of LVRR and cardiac event-free survival. Among all the baseline primary candidate factors with P < 0.2 as per univariate analysis, multivariate analysis indicated that only LGE area was an independent predictor of subsequent LVRR (β = 0.44; 95 % confidence interval (CI) 0.87–2.53; P < 0.001), as indicated by decreasing left ventricular end-systolic volume index over the 1-year follow-up. Kaplan–Meier curves indicated significantly lower cardiac event-free survival rates in patients with LGE at baseline than in patients without (P < 0.01). By contrast, there was no significant difference in prognosis between patients with CVF values above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox proportional hazard analysis showed that LGE area was an independent predictor of subsequent cardiac events (hazard ratio 1.06; 95 % CI 1.02–1.10; P ≤ 0.01). The degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that estimated by baseline EMB, can predict LVRR and cardiac event-free survival in response to therapy in patients with newly diagnosed IDCM.