Showing papers by "Susumu Kobayashi published in 2009"

Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK

Abstract: Purpose The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non–small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients and Methods Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Results Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and ...

Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance

Abstract: Purpose: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib benefit some non–small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance) and those who initially respond eventually progress (acquired resistance). EGFR TKI resistance is not completely understood and has been associated with certain EGFR and K-RAS mutations and MET amplification. Experimental Design: We hypothesized that dual inhibition of the vascular endothelial growth factor (VEGF) and EGFR pathways may overcome primary and acquired resistance. We investigated the VEGF receptor/EGFR TKI vandetanib, and the combination of bevacizumab and erlotinib in vivo using xenograft models of EGFR TKI sensitivity, primary resistance, and three models of acquired resistance, including models with mutated K-RAS and secondary EGFR T790M mutation. Results: Vandetanib, gefitinib, and erlotinib had similar profiles of in vitro activity and caused sustained tumor regressions in vivo in the sensitive HCC827 model. In all four resistant models, vandetanib and bevacizumab/erlotinib were significantly more effective than erlotinib or gefitinib alone. Erlotinib resistance was associated with a rise in both host and tumor-derived VEGF but not EGFR secondary mutations in the KRAS mutant-bearing A549 xenografts. Dual inhibition reduced tumor endothelial proliferation compared with VEGF or EGFR blockade alone, suggesting that the enhanced activity of dual inhibition is due at least in part to antiendothelial effects. Conclusion: These studies suggest that erlotinib resistance may be associated with a rise in both tumor cell and host stromal VEGF and that combined blockade of the VEGFR and EGFR pathways can abrogate primary or acquired resistance to EGFR TKIs. This approach merits further evaluation in NSCLC patients.

Importance of preoperative imaging with 64-row three-dimensional multidetector computed tomography for safer video-assisted thoracic surgery in lung cancer.

Abstract: Video-assisted thoracic surgery (VATS) has recently been adopted for complicated anatomical lung resections. During these thoracoscopic procedures, surgeons view the operative field on a two-dimensional (2-D) video monitor and cannot palpate the organ directly, thus frequently encountering anatomical difficulties. This study aimed to estimate the usefulness of preoperative three-dimensional (3-D) imaging of thoracic organs. We compared the preoperative 64-row three-dimensional multidetector computed tomography (3DMDCT) findings of lung cancer-affected thoracic organs to the operative findings. In comparison to the operative findings, the branches of pulmonary arteries, veins, and bronchi were well defined in the 3D-MDCT images of 27 patients. 3D-MDCT imaging is useful for preoperatively understanding the individual thoracic anatomy in lung cancer surgery. This modality can therefore contribute to safer anatomical pulmonary operations, especially in VATS.

Synthetic Study of (−)‐Norzoanthamine: Construction of the ABC Ring Moiety

Abstract: Ausgehend vom (−)-Hajos-Parrish-Keton gelang eine hoch diastereoselektive Synthese des ABC-Ringsystems von (−)-Norzoanthamin (siehe Schema). Die drei quartaren Kohlenstoffstereozentren am C-Ring wurden durch eine 1,4-Addition eingefuhrt, und eine intramolekulare Diels-Alder-Reaktion erzeugte das trans-Decalin-Gerust fur das AB-Ringsystem.

Total Synthesis of (−)-Norzoanthamine†

Abstract: No bones about it: (-)-Norzoanthamine, a promising candidate for an anti-osteoporotic drug, was the target of a total synthesis (see scheme). The final bisaminal formation with AcOH/H(2)O gave the DEFG ring, while the cyclization precursor was prepared by installing the remaining bisaminal unit after oxidative cleavage of the cyclopentanol moiety.

Small Symptomatic Pericardial Diverticula Treated by Video-Assisted Thoracic Surgical Resection

Abstract: There have been few reports about symptomatic pericardial diverticula. We describe 2 patients of symptomatic pericardial diverticula whose symptoms were relieved after surgery. The first patient complained of severe left anterior chest pain for a period of 6 months, and a pericardial diverticulum 4 × 3 cm in size was detected on the right side of the ascending aorta opposite the symptomatic side. The second patient complained of right anterior chest pain for a few months, and a pericardial diverticulum 6 × 2 cm in size was detected on the right side of the heart. Although these cysts did not appear large enough to cause symptoms, the patients underwent thoracoscopic resection. The postoperative course in each patient was uneventful, and the symptoms were relieved. We recommend that a symptomatic anterior mediastinal cyst be completely resected even if it does not appear large enough to compress the neighboring organs. (Ann Thorac Cardiovasc Surg 2009; 15: 123–125)

Therapeutic effect of balloon-occluded retrograde transvenous obliteration for gastric varices in relation to haemodynamics in the short gastric vein

Abstract: The aim of this study was to elucidate the relationship between the therapeutic effect of balloon-occluded retrograde transvenous obliteration (B-RTO) and haemodynamic features in the short gastric vein (SGV) in patients with gastric fundal varices (GV). The subjects in this retrospective cohort study comprised 34 patients who had moderate- or large-grade GV with the SGV both on retrograde venography and Doppler ultrasound. The diameter, flow velocity and flow volume in the SGV measured by Doppler ultrasound before B-RTO with 1 h balloon occlusion were compared with the therapeutic effect. Embolisation of GV was achieved in 30/34 patients (88.2%): 27 by initial B-RTO and 3 by second B-RTO. Flow velocity and flow volume in the SGV before B-RTO were significantly lower in the 27 patients with a complete effect on initial B-RTO (7.19+/-2.44 cm s(-1), p = 0.0246; 189.52+/-167.66 ml min(-1), p = 0.002) than in the 7 patients with an incomplete effect (10.41+/-5.44 cm s(-1), 492.14+/-344.94 ml min(-1)). Neither endoscopy nor contrast-enhanced CT had recurrent findings of GV in the subject during the follow-up period (94-1440 days; mean, 487.2+/-480.5 days). In conclusion, haemodynamic evaluation of the SGV using Doppler ultrasound may be useful for the prediction of the therapeutic effect of B-RTO.

Video-assisted thoracic surgery for recurrent primary spontaneous pneumothorax in reoperated chests.

Abstract: There are few reports on video-assisted thoracic surgery (VATS) for recurrent primary spontaneous pneumothorax (PSP) in reoperated chests. We report our experience of performing redo VATS for recurrent PSP in reoperated chests. Between July 1, 2005 and December 31, 2007, 55 patients at Jikei University Kashiwa Hospital and 80 patients at Jikei University Hospital underwent VATS for PSP. In this period, no patient underwent thoracotomy for PSP. Ten of these patients underwent surgery for recurrent PSP in a reoperated chest: five from our hospital and five who were referred from other institutions. Video-assisted thoracic surgery revealed minimal to strong adhesions in all ten patients. Nine patients underwent bullectomy using endoscopic staplers, and seven had covering pleural adhesions. There were no major complications or mortality, and no patient showed any sign of recurrence of PSP in the follow-up period. Redo VATS on a reoperated chest is a promising technique for treating recurrent PSP.

Temporary claviculectomy approach for plexiform neurofibroma of the first intercostal nerve.

Abstract: Plexiform neurofibroma at the thoracic inlet has rarely been reported and to our knowledge, the use of a temporary middle claviculectomy approach for thoracic inlet tumors has never been reported. We report a case of plexiform neurofibroma of the first intercostal nerve resected using a temporary claviculectomy approach. An abnormal shadow detected radiographically in a 16-year-old boy led to a diagnosis of neurofibromatosis 1 (NF-1) with a chest wall tumor at the thoracic inlet. The patient underwent resection of the tumor with the right first rib. The resected clavicle was reapproximated with a plate and postoperative shoulder function was satisfactory. The tumor was diagnosed pathologically as a plexiform neurofibroma and the patient’s postoperative course was uneventful. The temporary middle claviculectomy approach provides excellent exposure of the subclavian vessels and brachial plexus before resection of the tumor. We recommend this approach for tumors of the anterior thoracic inlet.

Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis.

Abstract: A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications.

Where is the Best Surgical Incision for Laparoscopic Anterior Resection

Abstract: BACKGROUND/AIMS For laparoscopic anterior resection, a small incision is placed in the left lower abdomen or suprapubic area, for which ideal location remains to be clarified. This study evaluated the validity of anthropometric placement of such an incision for colorectal anastomosis in laparoscopic anterior resection. METHODOLOGY Thirty consecutive patients with advanced rectal cancer (Age 30- 82 {mean 60.1} years, 15 men and 15 women) who underwent anterior resection by open surgery at Kashiwa Hospital between 2005 and 2006 were studied. The position of the viscera was projected on the anterior wall of the abdomen, in relation to the umbilicus. RESULTS Each visceral position (X cm, Y cm) was as follows; SD junction (6.3 +/- 1.6, -2.0 +/- 2.3), promontorium (0.0 +/- 0.0, -4.5 +/- 0.8), Douglas' pouch (0.0 +/- 0.0, -14.9 +/- 1.5) and superior margin of the pubis (0.0 +/- 0.0, -18.2 +/- 1.4). The positions of promontorium and the Douglas' pouch had little horizontal anatomical variation and were located between the umbilicus and the pubis. CONCLUSION In laparoscopic anterior resection, a small incision for transection of the rectum and colorectal anastomosis should be placed in the suprapubic area rather than the left lower abdomen.

Claisen Rearrangement UsingBicyclic 2-[(Z)-Alkenyl]dihydropyran: StereoselectiveSynthesis of trans-Substituted Spiro[4.5]decane

Abstract: We report the first example of the Claisen rearrangement in the 2-[(Z)-alkenyl]dihydropyran system yielding spiro[4.5]decane in a trans fashion. This protocol is useful for the synthesis of trans-substituted spiro[4.5]decanes, a potentially useful class of spirocyclic terpenes and alkaloids.

Stereocontrolled Total Synthesisof Antimalarial (+)-Axisonitrile-3

Abstract: Here we describe the total synthesis of the antimalarial sesquiterpene, (+)-axisonitrile-3 Three key features of this synthesis are: (i) non-Evans syn-aldol reaction of an isovaleric acid derivative bearing a chiral oxazolidinethione and crotonaldehyde with high diastereoselectivity, (ii) Claisen rearrangement of alkenyl dihydropyran affording spiro[45]decane with requisite functionalities, and (iii) highly stereoselective reduction in the sterically congested O-methyl oxime system

Total Synthesis of (‐)‐Diversifolin.

Abstract: First total synthesis of biologically active germacrane-type sesquiterpene (−)-diversifolin has been achieved. The features of the synthesis involve (i) ring-closing metathesis to give a 10-membered carbocycle, (ii) regioselective Mukaiyama aldol reaction of silyl dienol ether with formaldehyde at the α-position, and (iii) lactone transposition of the fully functionalized 11-oxabicyclo[6.2.1]undecane system.