Development of HER2-antagonistic peptides as novel anti-breast cancer drugs by in silico methods.

An antagonistic peptide called HRAP that binds to the human HER2 molecule was designed by our computational method. In silico docking study demonstrated the specific interaction of HRAP with the dimerization domain in the HER2 molecule. Interestingly, HRAP inhibited proliferation of HER2-overexpressed human breast cancer cell lines. However, it had little cellular cytotoxicity (apoptosis inducibility). The cell proliferation inhibition was associated with the suppression of phosphorylation of PTEN and Akt. Thus, HRAP is the first HER2-binding small peptide antagonist rationally designed by a computer-aided SBDD method and is useful for the development of peptide mimetics to generate novel anti-breast cancer drugs.     

Sonographic evaluation of the anterior liver surface in chronic liver diseases using a 7.5-MHz annular-array transducer: correlation with laparoscopic and histopathologic findings

PURPOSE: We studied the sonographic appearance of the anterior liver surface using an ultrasound scanner equipped with a 7.5-MHz annular-array transducer to determine the accuracy of this imaging modality in monitoring the course of chronic liver diseases. METHODS: We prospectively evaluated patterns of the liver surface in the sonograms of 77 consecutive patients with chronic liver diseases who had undergone sonographic examination with a 7.5-MHz annular-array transducer and a 3.75-MHz convex-array transducer over a 2-year period and compared these findings with those of laparoscopy (using previously described categories) and histopathology. RESULTS: Histopathologically confirmed disease prevalences for inactive chronic hepatitis, active chronic hepatitis, liver cirrhosis, and others were 10% (8/77), 56% (43/77), 29% (22/77), and 5% (4/77), respectively. The sonographic appearance of the liver surface with the 3.75-MHz transducer was classified as either a regular or an irregular pattern. The regular pattern corresponded to 69% (34/50) of the cases in laparoscopic category 200 or 300 and the irregular pattern with 85% (23/27) of the cases in category 400 or 500. The sonographic appearance of the liver surface with the 7.5-MHz transducer was classified as regular, unevenly irregular, diffusely irregular, or nodular. These 4 patterns detected 75% (24/32), 78% (14/18), 52% (12/23), and 75% (3/4) of the cases of laparoscopic categories 200, 300, 400, and 500, respectively. In a comparison of the sonographic patterns of the liver surface with the differential histopathologic findings, the regular sonographic pattern corresponded to 88% (7/8) of the cases of inactive chronic hepatitis, the unevenly irregular pattern with 35% (15/43) of the cases of active chronic hepatitis, and the diffusely irregular and nodular patterns (considered as 1 group) with 68% (15/22) of the cases of liver cirrhosis. CONCLUSIONS: Our results suggest that sonographic evaluation of the liver surface with a 7.5-MHz annular-array transducer using this classification provides detailed information on the evolution of chronic liver diseases that correlates with the laparoscopic and histopathologic findings and thus is a useful noninvasive method for monitoring the disease course to cirrhosis.     

Central Lymph Node Metastasis in Gastric Cancer Is Predictive of Survival After Preoperative Therapy

Background

It is unclear how preoperative therapy for gastric cancer affects the metastasis rate of lymph nodes (LNs) and whether the location of positive LNs affects survival after preoperative therapy. Therefore, we determined the association between positive central lymph nodes (CnLNs) and disease stage and overall survival (OS).

Methods

We reviewed a prospectively maintained database to identify patients who had undergone resection of gastric adenocarcinoma at our institution from 2005 to 2015. CnLNs were defined as common hepatic, celiac, and proximal splenic artery LNs (stations no. 8, 9, and 11p). The frequency of CnLN metastases and risk factors affecting OS were examined.

Results

We identified 356 patients. Preoperative therapy was administered to 66% of patients. D2 LN dissection was performed in 80% of patients, and the median number of LNs examined was 25 (IQR, 18–34). In 243 patients (68%), CnLNs had undergone separate pathologic examination; the CnLN-positive rate was 9.1% (22 of 243; station no. 8, 4.5%; no. 9, 2.1%; and no. 11p, 4.8%). CnLN metastasis was associated with shorter 3-year OS in patients with pN2/3 disease (33 vs. 62%; p?=?0.004). Among patients who had undergone preoperative therapy, ypT3–4 stage (HR 2.44; p?=?0.01) and positive CnLNs (HR 5.44; p?<?0.001) were negatively associated with OS by multivariate analysis.

Conclusions

CnLN metastases are uncommon in gastric cancer and have an adverse effect on OS in patients who have undergone preoperative therapy. Larger multi-institutional studies are needed to determine whether CnLN positivity requires a separate staging category after preoperative therapy.

     

Surgical Outcomes of Pancreaticoduodenectomy for Pancreatic Cancer with Proximal Dorsal Jejunal Vein Involvement

Background/Purpose

The proximal jejunal vein which branches from the dorsal side of the superior mesenteric vein (SMV) usually drains the inferior pancreatoduodenal veins (IPDVs) and contacts the uncinate process of the pancreas. We focused on this vein, termed the proximal dorsal jejunal vein (PDJV), and evaluated the anatomical classification of the PDJV and surgical outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) with PDJV involvement (PDJVI).

Methods

The jejunal veins that branch from the dorsal side of the SMV above the inferior border of the duodenum are defined as PDJVs. We investigated 121 patients who underwent upfront pancreaticoduodenectomy for PDAC between 2011 and 2017; PDJVs were resected in all patients. The anatomical classification of PDJV was evaluated using multidetector computed tomography. Surgical and prognostic outcomes of pancreticoduodenectomy for PDAC with PDJVI were evaluated.

Results

The PDJVs were classified into seven types depending on the position of the first and second jejunal veins relative to the superior mesenteric artery. In all patients, the morbidity and mortality rates were 15.7 and 0.8%, respectively. The rates for parameters including SMV resection, presence of pathological T3–4, R0 resection, and 3-year survival were 46.2, 92.3, 92.3, and 61.1%, respectively, when there was PDJVI (n?=?13). When there was no PDJVI (n?=?108), the rates were 60.2, 93.5, 86.1, and 58.3%, respectively. Overall, there were no significant differences.

Conclusions

Pancreaticoduodenectomy with PDJV resection is feasible for PDAC with PDJVI and satisfactory overall survival rates are achievable. It may be necessary to reconsider the resectability of PDAC with PDJVI.

     

The three-dimensional motions of glenohumeral joint under semi-loaded condition during arm abduction using vertically open MRI

BACKGROUND: Magnetic resonance imaging is an accurate non-invasive tool for visualizing muscles, tendons, and bones. It also provides 3D coordinate values. The purpose of the present study was to visualize and quantify the 3D positions of the glenohumeral joint during isometric abduction of the arm using vertically open magnetic resonance imaging. METHODS: We examined 14 shoulders of seven healthy volunteers. Magnetic resonance images were obtained in a seated position and in seven static positions of the arm from 0 degrees to maximum abduction using vertically open magnetic resonance imaging. 3D surface models were created and 3D movements of each bone in the glenohumeral joint were calculated using a computer algorithm. We analyzed the translation and contact pattern of the glenohumeral joint. FINDINGS: In supero-inferior direction, the humeral head translated slight inferiorly from +1.9 (SD 1.0) mm at 0 degrees to +0.8 (SD 1.8) mm at the maximum abduction. In antero-posterior direction, the humeral head translated anteriorly from 0 degrees to 90 degrees (mean +2.4, SD 2.6 mm) and posteriorly from 90 degrees to 150 degrees of abduction (mean -1.4, SD 2.7 mm). Furthermore, the humeral head had a unique contact patterns with the glenoid; the contact part of the humeral head with the glenoid changed from the central part to the posterior in the midrange of abduction. INTERPRETATION: The humeral head showed a small translation in the antero-posterior direction between 90 degrees and 150 degrees of abduction. In addition, the posterior part of the humeral head contacted the glenoid in this range of abduction. These findings of motion patterns in asymptomatic subjects will be necessary when comparing the kinematics with pathologic condition such as the glenohumeral instability and rotator cuff tear.     

Radiofrequency ablation in a porcine liver model： Effects of transcatheter arterial embolization with iodized oil on ablation time, maximum output, and coagulation diameter as well as angiographic characteristics

AIM:To evaluate the effects of combined radiofrequen-cy ablation and transcatheter arterial embolization with iodized oil on ablation time,maximum output,coagula-tion diameter,and portal angiography in a porcine liver model. METHODS: Radiofrequency ablation (RFA) was applied to in vivo livers of 10 normal pigs using a 17-gauge 3.0 cm expandable LeVeen RF needle electrode with or with-out transcatheter arterial embolization (TAE) with iodized oil (n = 5). In each animal,2 areas in the liver were ab-lated. Direct portography was performed before and af-ter RFA. Ablation was initiated at an output of 30 W,and continued with an increase of 10 W per minute until roll-off occurred. Ablation time and maximum output until roll-off,and coagulated tissue diameter were compared between the 2 groups. Angiographic changes on portog-raphy before and after ablation were also reviewed. RESULTS: For groups with and without TAE with iodized oil,the ablation times until roll-off were 320.6 ± 30.9 seconds and 445.1 ± 35.9 seconds,respectively,maxi-mum outputs were 69.0 ± 7.38 W and 87.0 ± 4.83 W and maximal diameters of coagulation were 41.7 ± 3.85 mm and 33.2 ± 2.28 mm. Significant reductions of abla-tion time and maximum output,and significantly larger coagulation diameter were obtained with RFA following TAE with iodized oil compared to RFA alone. Portography after RFA following TAE with iodized oil revealed more occlusion of the larger portal branches than with RFA alone. CONCLUSION: RFA following TAE with iodized oil can increase the volume of coagulation necrosis with lower output and shorter ablation time than RFA alone in nor-mal pig liver tissue.     

Pediatric pneumonia, pleural effusion, and pericarditis following cat scratch disease and serological cross-reactions among Bartonella henselae and Rickettsia japonica determined by indirect fluorescence antibodies

Cat scratch disease is associated with a variety of systemic manifestations. We report a pediatric case associated with pneumonia, pleural effusion, and pericarditis. A 3-year-old boy developed prolonged fever unresponsive to antibiotic treatment, including azithromycin and minocycline. Although the fever resolved with corticosteroid treatment, Bartonella henselae IgG titer was positive in indirect fluorescence antibodies, as was Rickettsia japonica IgG titer. Both titers were significantly reduced by serum absorption with B. henselae antigens, and we observed a serological cross-reaction between B. henselae and R. japonica.