<Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">BRAF</Emphasis> Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Living donor liver transplantation for the patients with portal vein thrombosis: use of an interpositional venous graft passed posteriorly to the pancreatic parenchyma without using jump graft

Background

It is difficult to reconstruct the portal vein (PV) using a long interpositional venous graft in living donor liver transplant (LDLT) patients with portal vein thrombosis (PVT), which involves the confluence of the superior mesenteric vein (SMV) and splenic vein (SV). We successfully performed LDLT for three patients with PVT using an interpositional vascular conduit passing posterior to the pancreas without a jump graft.

Methods

Three of 130 patients who underwent LDLT in our hospital between March 2002 and June 2011 required this technique. After indentifying the location of the SMV, SV and gastrocolic trunk, we ligated and cut the posterior superior pancreaticoduodenal vein and other short branches from the PV. The PV was drawn inferiorly to the pancreas and transected at the confluence of SMV and SV. The external iliac vein or internal jugular vein was sacrificed as a graft for anastomosis to the cut end of the SMV using 6-0 polypropylene running sutures. Then the venous graft was drawn superiorly to the pancreas by passing it posterior to the pancreas parenchyma for anastomosis to the liver graft PV. The interpositional vein was placed posterior to the pancreas where the PV used to be.

Results

All three patients displayed favorable postoperative courses with the Doppler ultrasound demonstrating good portal flow perioperatively. The postoperative portogram demonstrated patency of the vascular graft.

Conclusion

This method is easy and helpful to treat portal vein thrombosis, by providing the shortest route between the PV of the donor and the SMV of the recipient.     

Effect of pulsatile left ventricular assist system implantation on Doppler measurements of renal hemodynamics in patients with advanced heart failure

The effects of left ventricular assist system (LVAS) implantation on renal hemodynamics remains to be fully elucidated. We evaluated renal function and intrarenal blood flow in five advanced heart failure patients who had been supported with a Toyobo LVAS for bridge to heart transplantation. Renal function expressed as estimated glomerular filtration rate (eGFR) was calculated using the modified formula of Modification of Diet in Renal Disease. Mean blood velocities in the bilateral segmental arteries during systolic and diastolic perfusion were measured using duplex Doppler sonography, and renal vascular resistance (resistive index [RI]) of the segmental arteries was defined as (peak systolic velocity [PSV]-end-diastolic velocity [EDV])/PSV. All studies were performed before and after implantation (mean duration of support, 15.6±10.9 months). LVAS implantation significantly improved eGFR (42.7±7.9 to 64.1±16.3mL/min, P<0.05). Beat-by-beat measurements of heart rate did not change significantly. Mean PSV decreased significantly (38.2±8.9 to 28.3±2.2cm/s, P<0.05), and mean EDV increased significantly (8.3±3.2 to 11.3±1.3cm/s, P<0.05), and thus, mean RI was significantly improved (0.79±0.06 to 0.60±0.04, P<0.01). In conclusion, in advanced heart failure patients, pulsatile LVAS implantation is associated with improved renal function, and this improvement may be mediated in part through an improvement of intrarenal hemodynamics.     

Successful resection of thoracic esophageal cancer associated with the right aortic arch

A 52-year-old Japanese man with thoracic esophageal cancer associated with the right aortic arch was admitted to our hospital. Preoperative spiral computed tomography and three-dimensional image reconstruction also showed an associated aberrant left subclavian artery. After preoperative concurrent chemoradiation, the patient underwent a subtotal esophagectomy with regional lymphadenectomy via a left thoracotomy.     

Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.     

A rare case of 2 free thrombi in left atrium with mitral stenosis

A 64-year-old female was admitted with general fatigue and orthopnea. Preopertive echocardiography showed a free ball thrombus in the left atrium, mitral stenosis and severe tricuspid regurgitation. To avoid a herniation of thrombus to the mitral orifice, an emergency operation was performed. Two free and small mural thrombi were found in the left atrium. Thrombectomy, mitral valve replacement and tricuspid annuloplasty were performed successfully. Postoperative course was uneventful, and she was discharged in good condition on the 21st postoperative day.     

Impaired cutaneous wound healing in mice lacking tetranectin

Tetranectin was originally purified from human serum on the basis of plasminogen kringle 4-binding properties. Tetranectin enhances plasminogen activation by a tissue-type plasminogen activator so that it has been suggested to play a role in tissue remodeling. We have generated mice with a targeted disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision. However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process.     

Angiomyolipoma arising in the thigh

A 41-year-old man presented with an asymptomatic mass in the right medial thigh. Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the right adductor muscles. The margins of the mass exhibited high signal intensity and the rest showed low or iso signal intensity on T1-weighted MR images. However, the high signal intensity was decreased on T2-weighted images with fat suppression. The central part of the tumor was of inhomogeneous high signal intensity on T2-weighted images; after Gd-DTPA injection it enhanced inhomogeneously on T1-weighted images with fat suppression. On dynamic computed tomography (CT) in the arterial phase, there were strongly enhancing spotty areas in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological diagnosis of angiomyolipoma (AML) in the thigh was made. Received: 21 June 1999 Revision requested: 28 July 1999 Revision received: 13 December 1999 Accepted: 15 December 1999     

Bronchiolar disease: spectrum and radiological findings

Two types of bronchiole, the terminal bronchiole and the respiratory bronchiole, have structural and functional differences. The former is characterized as a conducting airway and the latter is closely related to a gas-exchange function as it has numerous alveoli on the wall. Therefore, the diseases occurring at bronchiole demonstrate different pathological, radiological and clinical pictures depending on which bronchiole is mainly involved. The disease that mainly involves the conducting airway is appreciated as a small airway disease. Constrictive bronchiolitis is a well-recognized entity classified in this category. Whereas the disease mainly involves the respiratory bronchiole and distal alveolar space, it is recognized as an interstitial and parenchymal disease. BOOP or RB-ILD is classified in this category. These two types of bronchiolar diseases reveal the contrast clinical pictures, including incidence, causative disease, response to the treatment, prognosis, respiratory function test as well as the radiological findings. This pictorial essay will illustrate the radiological features of the varieties of bronchiolitis.