[Show abstract][Hide abstract] ABSTRACT: Current chemotherapeutic regimens have only modest benefit for non-small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients.
Pieces (1x3x3 mm(3)) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area <or=50% of control, P < 0.05) were determined. Clinical outcomes of treated patients were acquired.
Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive.
Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients.
Clinical Cancer Research 02/2010; 16(5):1442-51. DOI:10.1158/1078-0432.CCR-09-2878 · 8.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cervical esophagogastric anastomoses are commonly used for reconstruction after esophagectomy because of the lower mortality rate associated with an anastomotic leak compared to intrathoracic anastomoses. However, cervical esophagogastric anastomoses have been criticized for their higher leak rates, stricture formation and greater need for later dilatations when compared with intrathoracic anastomoses. Multiple studies have looked at varying techniques to improve the outcome of the cervical esophagogastric anastomosis. This study was performed to determine whether a partially stapled (posterior stapled wall and anterior hand-sewn wall) anastomosis reliably reduced leaks and the need for later dilatation. From January 2001 to March 2006, 168 patients who underwent cervical esophagogastric anastomosis following esophagectomy (transhiatal or three-hole) for cancer were identified. Beginning in September 2003, the partially stapled technique was introduced and used in 79 patients. Clinical outcomes were compared to patients in whom hand-sewn technique was used (n = 89). Outcomes related to anastomotic leak, other hospital complications, length of stay, postoperative dilatations and survival were compared using Student's t-tests and chi-square tests (P < 0.05), as well as multiple regression analyses. An anastomotic leak occurred in 10 (12.7%) patients who received a partially stapled anastomosis. A hand-sewn anastomosis was complicated by an anastomotic leak in 24 patients (27.0%). This difference was statistically significant (P = 0.021). This lowered incidence of leak was associated with an earlier initiation of oral feeds (median 7 vs. 9.5 days, P < 0.001) and a reduction in hospital stay (median 10 vs. 15 days, P < 0.001). Furthermore, dysphagia associated with stricture requiring postoperative dilatations was markedly diminished in the stapled anastomosis [23 (31.3%) vs. 49 (55.1%), P = 0.001]. The partially stapled cervical esophagogastric anastomosis significantly decreased the incidence of postoperative anastomotic leaks and the need for postoperative dilatation to treat strictures compared to the hand-sewn anastomosis.
Diseases of the Esophagus 08/2008; 21(5):422-9. DOI:10.1111/j.1442-2050.2007.00792.x · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin (CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A (WNT5A)/ frizzled homolog 2 (FZD2), frizzled homolog 3 (FZD3) / dishevelled 2 (DVL2), and low density lipoprotein receptor-related protein 5 (LRP5)/ secreted frizzled-related protein 4 (SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess the validity of using a pulsatile, pressure waveform transduced from the epidural space through an epidural needle or catheter to confirm correct placement for maximal analgesia and to compare 3 different types of catheters' ability to transduce a waveform.
A single-center, prospective, randomized trial.
A tertiary-referral hospital.
Eighty-one patients undergoing posterolateral thoracotomy who required a thoracic epidural catheter for postoperative pain management.
Each epidural needle and each epidural catheter was transduced to determine if there was a pulsatile waveform exhibited.
Sensitivity of the pulsatile waveform transduced through an epidural needle to identify correct placement of the epidural needle and the sensitivity of each catheter type to identify placement were compared. In 79 of 81 cases (97.5%), the waveform transduced directly through the epidural needle had a pulsatile characteristic as determined by blinded observers. In a total of 53 of 81 epidural catheters (65.4%), the transduced waveform displayed pulsations. Twenty-four of 27 catheters in group S-P/Sims Portex (Smiths Medical MD, Inc, St Paul, MN) (88.9%) transduced a pulsatile tracing from the epidural space, a significantly greater percentage than in the other 2 groups (p = 0.02).
The technique of transducing the pressure waveform from the epidural needle inserted in the epidural space is a sensitive and reliable alternative to other techniques for confirmation of correct epidural catheter placement. The technique is simple, sensitive, and inexpensive and uses equipment available in any operating room.
Journal of Cardiothoracic and Vascular Anesthesia 11/2006; 20(5):659-63. DOI:10.1053/j.jvca.2006.02.022 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The frequency and causes of gastrointestinal complications following esophagectomy for malignancy are unknown.
We reviewed 295 esophagectomies performed for malignancy between January 1980 and September 1994 in order to determine the frequency and causes of early and late gastrointestinal complications.
Compared to transhiatal and left thoracoabdominal esophagectomies, esophagectomies carried out through a right posterolateral thoracotomy with cervical esophagogastric anastomosis had a higher incidence of delayed gastric emptying (11%), pneumonia (26%), and hospital death (9%). The same operation had a higher incidence of gastroesophageal reflux (20%) and dysphagia requiring esophageal dilatation (53%). We found no independent effect of gastric drainage procedures, feeding jejunostomy, preoperative radiotherapy, pathology, or age on these outcomes. Women had no operative mortality, but a higher incidence of gastroesophageal reflux and diarrhea following esophagectomy.
Surgical techniques aimed at improving gastric emptying following esophagectomy for cancer should improve operative morbidity and mortality.
The American Journal of Surgery 06/1995; 169(5):471-5. DOI:10.1016/S0002-9610(99)80197-4 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A variant left hepatic artery occurs at a rate of approximately 10%. In standard esophagogastrectomy and some proximal gastric operations this variant artery is sacrificed, which has led to reported fatalities secondary to hepatic necrosis. We report our method of esophagogastrectomy in the presence of an aberrant left hepatic artery.
The Annals of Thoracic Surgery 08/1992; 54(1):166-8. DOI:10.1016/0003-4975(92)91173-7 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Following esophagectomy, restoration of swallowing by gastric tube interposition with cervical esophagogastric anastomosis reduces morbidity and mortality associated with intrathoracic anastomoses at the expense of an increased incidence of both anastomotic leak and stricture formation. A retrospective study of 165 patients with either squamous cell carcinoma or adenocarcinoma of the distal esophagus or gastric cardia undergoing esophagogastrectomy with gastric tube interposition and cervical anastomosis at Vancouver, British Columbia, or London, Ontario, was undertaken. Forced-entry multiple logistic regression analysis of factors believed to influence anastomotic outcome was performed. Anastomotic leak occurred in 17% of patients; statistically significant correlation with low preoperative serum albumin (p = 0.005), running suture technique (p = 0.029), high intraoperative blood loss (p = 0.038), and the occurrence of postoperative delayed gastric emptying (p = 0.045) was found. Anastomotic strictures occurred in 31% of patients; a statistically significant correlation was found with preceding anastomotic leak (p = 0.001) and intraoperative blood loss (p = 0.042). Factors including preoperative radiotherapy and diabetes mellitus were not found to be significant.
The American Journal of Surgery 06/1992; 163(5):484-9. DOI:10.1016/0002-9610(92)90393-6 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thirty-four patients undergoing thoracotomy were entered into a randomized, double-blind, placebo-controlled study to compare the effects of patient-controlled, lumbar epidural (PCA-E) fentanyl with patient-controlled intravenous (PCA-i.v.) fentanyl with respect to drug requirements, analgesic efficacy and respiratory function. Prior to chest closure patients received fentanyl 2 micrograms.kg-1 by the epidural or i.v. route. In the recovery room further doses of epidural or i.v. fentanyl, 50 micrograms, were administered by the patients who controlled two PCA pumps. Background fentanyl infusion rates were increased by 10 micrograms.hr-1 each time the patient administered a drug bolus and were decreased by 10 micrograms.hr-1 whenever visual analogue scale (VAS) pain scores were less than 2 on a maximum 10 scale. Twenty-nine patients completed the study. Patients in the PCA-E group (n = 14) required less total fentanyl than those in the PCA-i.v. (n = 15) group (1857 +/- 693 micrograms vs 2573 +/- 890 micrograms respectively, P less than 0.05). Fentanyl infusion rates were lower in the PCA-E group at most measurement times. There were no differences between groups in respiratory rates, PaCO2, VAS pain scores or changes in pulmonary function as measured by FVC and FEV1. It is concluded that satisfactory patient-controlled analgesia can be achieved with both epidural and i.v. fentanyl after thoracotomy but that fentanyl requirements are less when given via the epidural route. This supports a direct spinal cord site of action for lumbar epidural fentanyl.
Canadian Journal of Anaesthesia 04/1992; 39(3):214-9. DOI:10.1007/BF03008779 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of fibrin glue as a sealant to reduce postoperative air leaks after pulmonary lobectomy was evaluated in 28 consecutive patients between November 1988 and May 1989. A fibrin glue spray was used in 14 patients, and 14 patients served as controls. Assignment of either group was made before thoracotomy. Nine male and 5 female patients with a mean age of 63.8 years were in the fibrin glue experimental group, and 8 male and 6 female patients with a mean age of 59 years, in the control group. An equal number of complete and incomplete fissures were in each group. All fissures were handled in the same way (stapled). Two milliliters of fibrin glue was applied through a double-syringe delivery system and sprayed on the staple line and any cut surface of the inflated lung just before thoracotomy closure. The fibrin glue-treated group had a mean air leak duration of 2.3 +/- 3.7 days, chest tube drains for 6 +/- 4.1 days, and a postoperative hospitalization of 9.8 +/- 3.1 days. The control group had a mean air leak duration of 3.3 +/- 3.3 days (p = 0.94), chest tube drains for 5.9 +/- 3.9 days (p = 0.95), and a postoperative hospitalization of 11.5 +/- 3.9 days (p = 0.21). We conclude that the routine use of a fixed quantity of fibrin glue is not effective in reducing the duration of air leaks, chest tube drainage, or hospitalization after uncomplicated pulmonary lobectomy.
The Annals of Thoracic Surgery 02/1990; 49(1):133-4. DOI:10.1016/0003-4975(90)90371-C · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the sensitivity of diffusing capacity (DLCO) and pressure-volume (P-V) curves in the detection of emphysema, these tests were compared with pathologic assessment of emphysema in patients undergoing lung resection for a localized tumor, and with the overall extent of emphysema as assessed by computed tomography (CT). The resected lung specimens were fixed in the inflated state and cut at 1-cm intervals in the horizontal plane. The pathologic extent of emphysema was quantitated by comparison with a standard reference panel of emphysema grading. The overall extent of emphysema on CT was assessed by a visual scoring system in a total of 55 patients, 19 undergoing lung resection and 36 not undergoing lung resection. Analysis of 37 patients by pathology scores revealed 18 with no or trivial emphysema (emphysema grades less than or equal to 5; mean grade, 2.2 +/- SD 2.6) and 19 with emphysema (grades greater than or equal to 10; mean grade, 33.2 +/- SD 24.2). Diffusing capacity, the ratio of DLCO to alveolar volume (DLCO/VA), maximal lung elastic recoil (PLmax), and lung elastic recoil at 90% of total lung capacity (PL90) were significantly different between the two groups, whereas K (the exponential constant describing the shape of the P-V curve) was not. The pathology grade of emphysema showed a significant correlation with (DLCO) (r = -0.53) and DLCO/VA (r = -0.55), which was greater than the correlation with PLmax (r = -0.42) and PL90 (r = -0.43).(ABSTRACT TRUNCATED AT 250 WORDS)
The American review of respiratory disease 06/1989; 139(5):1179-87. DOI:10.1164/ajrccm/139.5.1179 · 10.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1- to 1-cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1- to 2-mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively.
Cancer 04/1988; 61(5):1009-14. DOI:10.1002/1097-0142(19880301)61:53.0.CO;2-L · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been said that the lingula and right middle lobe should be avoided for open-lung biopsy because of nonspecific fibrosis and vascular changes. To determine if the diagnostic yields of lingular or right middle lobe biopsy specimens were unsatisfactory, we reviewed the results of open-lung biopsy in 73 adult patients; 26 were immunocompromised and 47, nonimmunocompromised. We found no evidence to suggest that these two sites were inherently inferior. In 20 of the nonimmunocompromised patients, computed tomography was performed prior to biopsy, and demonstrated no particular tendency for greater involvement of the lingula or right middle lobe. We conclude that lingular and right middle lobe biopsy is useful in the diagnosis of parenchymal lung disease and that these sites should not necessarily be avoided. Computed tomographic scanning prior to biopsy is helpful in guiding the surgeon to the appropriate sites from which to obtain biopsy specimens.
The Annals of Thoracic Surgery 10/1987; 44(3):269-73. DOI:10.1016/S0003-4975(10)62071-1 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether computerized tomography (CT) and radionuclide quantitative ventilation-perfusion lung scan add any useful information to a carefully performed endoscopic examination in determining the response of patients with obstructive endobronchial tumors to laser treatment, the findings in 40 patients treated with photodynamic therapy (PDT) or the Nd:YAG laser were analysed. Endoscopic laser treatment was found to be most effective when the tumor was polypoid in appearance bronchoscopically, with little or no submucosal invasion or peribronchial extension seen on CT. When bronchoscopy and CT showed increasing submucosal and/or peribronchial disease, the immediate and long-term response to treatment was poorer. CT provided valuable information regarding the extent of the peribronchial involvement and airway distortion which were often underestimated by bronchoscopy alone. Reduction of regional perfusion out of proportion to ventilation on scintigraphy in the involved lung zone was found to be associated with extensive peribronchial involvement. We conclude that the addition of CT and radionuclide quantitative ventilation-perfusion lung scan to bronchoscopic examination is useful in predicting the response of patients with obstructive endobronchial tumors to laser treatment. Whether PDT or YAG laser is more effective in relieving endobronchial obstruction by tumor awaits a randomized controlled trial.
Lasers in Surgery and Medicine 01/1987; 7(1):29-35. DOI:10.1002/lsm.1900070106 · 2.62 Impact Factor