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951.
Jocelyn F. Burke MD Logan Schlosser BS April D. Harrison BS Muthusamy Kunnimalaiyaan PhD Herbert Chen MD FACS 《Annals of surgical oncology》2013,20(12):3862-3868
Background
Development of targeted therapies for medullary thyroid cancer (MTC) has focused on inhibition of the rearranged during transfection (RET) proto-oncogene. Akt has been demonstrated to be a downstream target of RET via the key mediator phosphoinositide-3-kinase. MK-2206 is an orally administered allosteric Akt inhibitor that has exhibited minimal toxicity in phase I trials. We explored the antitumor effects of this compound in MTC.Methods
Human MTC-TT cells were treated with MK-2206 (0–20 μM) for 8 days. Assays for cell viability were performed at multiple time points with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The mechanism of action, mechanism of growth inhibition, and production of neuroendocrine tumor markers were assessed with Western blot analysis.Results
MK-2206 suppressed MTC cell proliferation in a dose-dependent manner (p ≤ 0.001). Levels of Akt phosphorylated at serine 473 declined with increasing doses of MK-2206, indicating successful Akt inhibition. The apoptotic proteins cleaved poly (ADP-ribose) polymerase and cleaved caspase-3 increased in a dose-dependent manner with MK-2206, while the apoptosis inhibitor survivin was markedly reduced. Importantly, the antitumor effects of MK-2206 were independent of RET inhibition, as the levels of RET protein were not blocked.Conclusions
MK-2206 significantly suppresses MTC proliferation without RET inhibition. Given its high oral bioavailability and low toxicity profile, phase II studies with this drug alone or in combination with RET inhibitors are warranted. 相似文献952.
Endovascular versus open approach to aortic aneurysm repair surgery: rates of postoperative delirium
Konrad Salata BHSc Rita Katznelson MD W. Scott Beattie MD PhD Jo Carroll RN Thomas F. Lindsay MD George Djaiani MD 《Journal canadien d'anesthésie》2012,59(6):556-561
Purpose
Our objective was to compare open and endovascular aortic aneurysm repair with respect to postoperative delirium.Methods
After Institutional Ethics Review Board approval, we conducted a retrospective review of all patients who underwent abdominal and thoraco-abdominal aortic aneurysm repair surgery at Toronto General Hospital during June 2006 to December 2007. Patients were classed into either the OPEN or the endovascular (EVAR) group based on the type of surgery and were assessed for the presence of delirium after surgery. The NEECHAM Confusion Scale and the validated chart review instrument were used for diagnosis of delirium. Patients with dementia and/or abnormal levels of consciousness preoperatively were excluded.Results
There were 256 patients included in the study, 149 (58%) in the OPEN group and 107 (42%) in the EVAR group. Patients in the EVAR group were considerably older, 74 (10) yr vs 68 (9) yr, and they had shorter duration of surgery, 150 [119, 180] min vs 200 [165, 260] min, respectively, P?<?0.0001. Postoperative delirium was present in 43 (29%) patients in the OPEN group and 14 (13%) patients in the EVAR group (95% confidence interval [CI], 22 to 36 vs 95% CI, 7 to 19, respectively; P?=?0.003). Hospital length of stay was 8.3 [6.6, 13.4] days in the OPEN group and 4.5 [3.1, 6.4] days in the EVAR group, P?<?0.0001.Conclusions
Perioperative management of patients undergoing endovascular aortic aneurysm repair was associated with lower rates of delirium after surgery than that of patients undergoing open aortic aneurysm repair. 相似文献953.
Dikken JL van de Velde CJ Gönen M Verheij M Brennan MF Coit DG 《Annals of surgical oncology》2012,19(8):2443-2451
Purpose
To evaluate the changes in the 7th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the 6th edition; to compare the predictive accuracy of the two staging systems.Methods
In a combined database containing 2,196 patients who underwent an R0 resection for gastric adenocarcinoma, differences between the two staging systems were evaluated and stage-specific survival estimates compared. Concordance probability and Brier scores were estimated for both systems to examine the predictive accuracy.Results
Nodal status cutoff values were changed, leading to a more even distribution for the redefined N1, N2, and N3 group. AJCC 6th edition stage II reflected a highly heterogeneous population, which is now adequately subdivided in the AJCC 7th edition into stages IIA, IIB, and IIIA. The predictive accuracy of N classification improved significantly as measured by concordance. Despite increased complexity, the predictive accuracy of AJCC 7th stage grouping was significantly worse than that of the AJCC 6th edition.Discussion
The increased complexity of the 7th edition staging system is accompanied by improvements in the predictive value of nodal staging as compared to the 6th edition, but it was no better in overall stage-specific predictive accuracy. Future refinements of the tumor, node, metastasis staging system should consider whether increased complexity is balanced by improved prognostic accuracy. 相似文献954.
Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer 总被引:1,自引:0,他引:1
White RR Xie HB Gottfried MR Czito BG Hurwitz HI Morse MA Blobe GC Paulson EK Baillie J Branch MS Jowell PS Clary BM Pappas TN Tyler DS 《Annals of surgical oncology》2005,12(3):214-221
Background Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. Methods Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.Results The estimated overall survival (median±SE) in the entire group of patients undergoing resection was 23±4.2 months, with an estimated 3-year survival of 37%±6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.Conclusions Histological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy. 相似文献
955.
Sang Eok Lee MD Young-Woo Kim MD Jun Ho Lee MD Keun Won Ryu MD Soo Jeong Cho MD Jong Yeul Lee MD Chan Gyoo Kim MD Il Ju Choi MD Myeong-Cherl Kook MD Byung-Ho Nam PhD Sook Ryun Park MD Min Ju Kim MD Jong Seok Lee MD 《Annals of surgical oncology》2009,16(8):2231-2236
Background The technical difficulty of lymph node dissection in laparoscopy-assisted distal gastrectomy (LADG) remains a barrier for
extending the indication for this modality and limits its widespread clinical practice. The aim of this study was to evaluate
our institutional guidelines for LADG, limiting the indications for this modality to only clinical stage T1N0 or T1N1 gastric
cancer.
Methods From January 2002 to October 2006, a total of 294 cases of LADG and 664 cases of open distal gastrectomy (ODG) for clinical
T1N0 or T1N1 gastric cancer were performed at the National Cancer Center, Korea. The two groups’ clinicopathologic characteristics,
surgical outcome, morbidity, and survival were compared.
Results The mean operating time for the LADG group was significantly longer than that for the ODG group (265.8 ± 56.3 vs. 171.4 ± 43.1
minutes, P < .001). The mean number of retrieved lymph nodes in the LADG group was higher than that of the ODG group (39.5 ± 14.7 vs.
37.2 ± 12.9, P = .017). The postoperative hospital stay was shorter in the LADG group (8.0 ± 3.3 vs. 10.5 ± 4.1 days, P < .001). The complications rate was lower for the LADG group than that for the ODG group (6.8% vs. 11.3%, P = .032). The overall survival rate was not significantly different between the two groups (P = .880).
Conclusions Before considering expanding the indications for LADG, developing a carefully thought-out guideline and conducting an audit
are mandatory. 相似文献
956.
Subareolar and peritumoral injection identify similar sentinel nodes for breast cancer 总被引:9,自引:0,他引:9
Bauer TW Spitz FR Callans LS Alavi A Mick R Weinstein SP Bedrosian I Fraker DL Bauer TL Czerniecki BJ 《Annals of surgical oncology》2002,9(2):169-176
Background Sentinel lymph node (SLN) mapping with radioisotope and blue dye is rapidly becoming the standard of care for breast cancer.
The optimal location for injection of radioisotope and blue dye is still being investigated. The goal of this study was to
determine whether blue dye injection into the subareolar (SA) location localized the same sentinel nodes as the peritumoral
(PT) location for patients with breast cancer.
Methods Three hundred thirty-two patients with biopsy-proven operable breast cancer or ductal carcinoma in situ at two institutions
underwent SLN mapping. Eighty-three patients had PT injection of blue dye (group 1), and 249 patients had SA injection of
blue dye (group 2). All patients underwent PT injection of99mTc-labeled sulfur colloid.
Results The two groups were similar in age, previous biopsy type, and tumor size, location, and histology. The mean number of SLNs
identified was 2.4 (range, 0–9) in group 1 and 2.5 (range, 0–11) in group 2. The SLN identification rate was 95% for group
1 and 97% for group 2. The isotope success rate was 94% for both groups. The blue dye success rate was 84% for group 1 and
90% for group 2. The isotope/blue dye concordance rate was 87% for group 1 and 90% for group 2. At a median follow-up of 28
months (range, 14 to 40), there were no axillary recurrences in any of the 332 patients.
Conclusions These data suggest that delivery of mapping reagents in the SA and PT locations identifies similar lymph nodes. Because of
simplicity and the similarity in node identification between SA and PT injection, further investigation of the SA site for
delivery of SLN mapping reagents for breast cancer is warranted.
Presented at the 54th Annual Cancer Symposium, Society of Surgical Oncology. Washington, DC, March 15–18, 2001. 相似文献
957.
Danielle M. Bello MD Ronald P. DeMatteo MD Charlotte E. Ariyan MD PhD 《Annals of surgical oncology》2014,21(6):2059-2067
The high response rates to the tyrosine kinase inhibitor imatinib in KIT-mutated gastrointestinal stromal tumors (GIST) has led to a paradigm shift in cancer treatment. In a parallel fashion, the field of melanoma is shifting with the utilization of targeted therapy to treat BRAF-mutated melanoma. We reviewed published literature in PubMed on GIST and melanoma, with a focus on both past and current clinical trials. The data presented centers on imatinib, vemurafenib, and most recently dabrafenib, targeting KIT and BRAF mutations and their outcomes in GIST and melanoma. The BRAFV600E melanoma mutation, like the KIT exon 11 mutation in GIST, has the highest response to therapy. High response rates with inhibition of KIT in GIST have not been recapitulated in KIT-mutated melanoma. Median time to resistance to targeted agents occurs in ~7 months with BRAF inhibitors and 2 years for imatinib in GIST. In GIST, the development of secondary mutations leads to resistance; however, there have been no similar gatekeeper mutations found in melanoma. Although surgery remains an important component of the treatment of early GIST and melanoma, surgeons will need to continue to define the thresholds and timing for operation in the setting of metastatic disease with improved targeted therapies. Combination treatment strategies may result in more successful clinical outcomes in the management of melanoma in the future. 相似文献
958.
Beechey-Newman N Kothari A Kulkarni D Hamed H Fentiman IS 《World journal of surgery》2006,30(1):63-68
This study was designed to assess the efficacy and long-term outcome of fistulectomy and saucerization for treatment of mammary
duct fistulae. Mammary fistula is a chronic condition that represents the final step in what has been termed “mammary duct
associated inflammatory disease sequence.” The treatment is primarily surgical and may include healing by secondary intention
or primary closure with or without antibiotics. Reported series are small and often include variable surgical strategies applied
without consistency. A consecutive series of 53 patients who had 59 mammary duct fistulae were treated by fistulectomy with
saucerization. The median age was 32 years. Wounds were allowed to heal by secondary intention and antibiotics were not used.
We reviewed the case records to establish the incidence of recurrent fistula and the time to complete healing. The long-term
cosmetic outcome was determined by a postal survey. After a median follow-up of 6 years there had been no relapse in 92%.
There was significant delay in healing in six cases (range: 10 to 30 weeks). Thirty-eight patients (83%) gave a definite history
of regularly smoking between 10 and 20 cigarettes a day. Two thirds of the patients were either pleased or satisfied with
the final cosmetic result of the surgery, but more than 90% said that it left them with some distortion of the nipple. Fistulectomy
and saucerization achieves long-term cure in the majority of patients with mammary duct fistula, but it results in some degree
of distortion of the nipple. The strong relationship between smoking and the occurrence of mammary duct fistulae is again
demonstrated. 相似文献
959.
Chang-Hsien Liu MD Chih-Yung Yu MD Wei-Chou Chang MD Ming-Shen Dai MD PhD Cheng-Wen Hsiao MD Yu-Ching Chou PhD 《Annals of surgical oncology》2014,21(9):3090-3095
Background
Although radiofrequency ablation (RFA) of nonresectable hepatic metastases has gained wide acceptance by showing survival benefit in selected patients, scattered reports are available regarding risk factors of local control of percutaneous RFA. The purpose of this study was to prospectively evaluate the factors influencing local tumor progression after percutaneous RFA of hepatic metastases.Methods
Sixty-nine hepatic metastatic lesions in 54 patients were treated by percutaneous RFA. Efficacy was evaluated by contrast-enhanced computed tomography or magnetic resonance imaging at 1 month after ablation, then at 3-month intervals for the first year and biannually thereafter.Results
The results of the log-rank test showed that tumor size of <3 cm (p = 0.024) and the absence of tumor contiguous with large vessels (p = 0.002) significantly correlated with local control for hepatic metastases. Cox regression analysis showed that the tumor size <3 cm and the absence of tumor contiguous with large vessels were independent factors (p = 0.055 and 0.009, respectively). The results of the log-rank test showed that neither the threshold post-ablation margin of 1.8 cm (p = 0.064) nor the presence of a tumor with subcapsular location (p = 0.134) correlated with the success of local control.Conclusions
Percutaneous RFA is more effective in achieving local control in patients with hepatic metastases when the tumor size is <3 cm and not contiguous with large vessels. 相似文献960.
Polyethylene glycol fusion associated with antioxidants: A new promise in the treatment of traumatic facial paralysis 下载免费PDF全文