Our Research

Presentations

2002

  • Roux-en-y Reconstruction for Treatment of Bile Reflux after Distal Esophagectomy. North Texas Chapter American College of Surgeons, Feb 2002.
  • Establishing a Laparoscopic Gastric Bypass Program: Prospective Analysis of the First 100 Patients. Southwestern Surgical Congress, April 2002.
  • Precedex: A Novel Approach to Acute Pain Management in Roux-en-y Gastric Bypass Patients. North Texas Chapter American College of Surgeons, Feb 2002; American Society of Bariatric Surgery, June 2002.

2003

  • A Prospective Randomized Double Blinded Clinical Trial of Dexmedetomidine in the Acute Postoperative Pain Management of Bariatric Surgical Patients. North Texas Chapter American College of Surgeons, Feb 2003 and American Society of Bariatric Surgeons, June 2003.
  • Laparoscopic Roux-en-y Gastric Bypass: A Comparison Study of Morbidly Obese Versus Super Morbidly Obese Patients. Southwestern Surgical Congress, April 2003.
  • The Role of Routine Upper GI Series Following Roux-en-Y Gastric Bypass. North Texas Chapter American College of Surgeons, Feb 2003 and American Society of Bariatric Surgery, June 2003.

2004

  • Comparisonof Retrocolic vs Antecolic Roux-en-y Limbs in Gastric Bypass. NorthTexas Chapter American College of Surgeons, Feb 2004.
  • Outpatient Laparoscopic Gastric Bypass: an Analysis of 1000 ConsecutiveCases. North Texas Chapter American College of Surgeons, Feb 2004.
  • Establishing a Bariatric Program. Miniworkshop Southwestern Surgical Congress, April 2004.
  • Internal Hernias After Laparoscopic Roux-en-y Gastric Bypass. Southwestern Surgical Congress, April 2004.
  • Outpatient Laparoscopic Gastric Bypass: Analysis of 1000 consecutive Cases. American Society of Bariatric Surgery, June 2004.
  • Preoperative vs Postoperative Administration of Low Molecular WeightHeparin for Laparoscopic Gastric Bypass. American Society of BariatricSurgery, June 2004.
  • Comparison of Retrocolic vs Antecolic roux-en-y Limbs in Gastric bypass. American Society of Bariatric Surgery, June 2004.
  • ReducingNausea and Hospital Length of Stay Laparoscopic Gastric Bypass Using anIntra-operative Steroid Bolus. American Society for Bariatric Surgery,June 2004.

2005

  • Use of Local Anesthetic Infusion Catheter in Laparoscopic GastricBypass Patients. North Texas Chapter American College of Surgeons, Feb2005.
  • Internal Hernias Following Antecolic Laparoscopic Roux-en-y GastricBypass. North Texas Chapter American College of Surgeons, Feb 2005.
  • The utility of Capsule Endoscopy and its Role for Diagnosing Pathologyin the GI Tract. Southwestern Surgical Congress, April 2005.
  • Optimizing Outcomes in Bariatric Surgery patients. American Surgical Association, May 2005.

2006-2007

  • Management of Gastrogastric Fistulas in the Roux-en-y Gastric BypassPatient. North Texas Chapter American College of Surgeons Feb 2006,Southwestern Surgical Congress April 2006.
  • Impact of Tissue Extraction Bag and Local Anesthetic Catheter on WoundInfection in Laparoscopic Gastric Bypass. North Texas Chapter AmericanCollege of Surgeons, Feb 2006, Southwestern Surgical Congress, April2006.
  • Incidence and Predictors of Cholecystectomy Following roux-en-y GastricBypass Without Cholelitholytic Drug Therapy. North Texas ChapterAmerican College of Surgeons, Feb 2006, Texas Weight Loss Summit, Jan2007.
  • Pregnancy Outcomes After Gastric Bypass Surgery. Southwestern Surgical Congress, April 2006.
  • Use of Peristrips in Laparoscopic Gastric Bypass. Texas Weight Loss Summit, Jan 2007.
  • Long-Term Concerns and Challenges for the Lap Band Patient, Texas Weight Loss Summit, Jan 2007.
  • Comparison of Reinforcd Circular Staple Lines and Non-reinforced StapleLines in Laparoscopic Roux-en-y Bypass Patients, North Texas ChapterAmerican College of Surgeons, Feb 2007.
  • Laparoscopic Esophagectomy. North Texas Chapter American College of Surgeons, Feb 2007.
  • Preoperative Micronutrient Deficiency in Morbidly Obese Patients. North Texas Chapter American College of Surgeons, Feb 2007.

2008-2009

  • Sleeve Gastrectomy: One Year Results. 4th Annual Texas Bariatric Meeting, Jan 2008.
  • Circular Staple Line Reinforcement: Impact on Leaks, Bleeding, and Weight Loss. 4th Annual Texas Bariatric Meeting, Jan 2008.
  • Prevention of Mesenteric Hernias with Closure and Fibrin Sealant. 4th Annual Texas Bariatric Meeting, Jan 2008.
  • Preventionof Deep Venous Thrombosis using a Short Course of Lovenox in Low Risk Bariatric Patients. 4th Annual Texas Bariatric Meeting, Jan 2008.
  • Use of Fibrin Glue for Closure of Mesenteric Defects-Improved Outcomes and Decreased Symptomatic Hernias. Oral Presentation North Texas Chapter American College of Surgeons, Feb 2008.
  • Circular Staple Line Reinforcement-One Year Results. Oral Presentation. North Texas Chapter American College of Surgeons, Feb 2008
  • Outcomes and Complications of Laparoscopic Sleeve Gastrectomy. Oral Presentation. North Texas Chapter American College of Surgeons, Feb 2008.
  • Venous Thromboembolic Events and Risk Stratification: Evaluation of Prolonged Prophylaxis in High Risk Bariatric Patients. Oral Presentation. North Texas Chapter American College of Surgeons, Feb 2008.
  • Anterior versus Trans-staple line gastrojejunostomy. Moving towards an optimal technique. Poster presentation. American Society of Metabolic and Bariatric Surgery, Oral Presentation, North Texas Chapter American College of Surgeons, February 2009.
  • Minimally Invasive Treatment of SMA Syndrome after Laparoscopic Roux-Y Gastric Bypass, Oral Presentation, North Texas Chapter American College of Surgeons, February 2009.
  • Surgical weight loss over 65 – is it worth the risk? Oral Presentation, North Texas Chapter American College of Surgeons, February 2009, Oral Presentation, American Society of Metabolic and Bariatric Surgery, June 2009.

2010-Present

  • Endoscopic Sclerotherapy for Stomal Dilation. Oral Presentaion North Texas Chapter American College of Surgeons February 2010,Poster Presentation American Society of Metabolic and Bariatric Surgery, June 2010.
  • Laparoscopic Bands Over Age 65—Realistic Expectations. Oral Presentation North Texas Chapter American College of Surgeons February 2010, Poster Presentation American Society of Metabolic and Bariatric Surgery, June 2010.
  • Revisional Bariatric Surgery.Texas Association of Bariatric Surgery, January 2010.
  • The Contribution of Malabsorption to the Reduction in Net Energy Absorption after long-limb Roux-en-Y gastric bypass. The American Journal of Clinical Nutrition 2010.

 

Publications

General and Oncology Research

Thyroid

The effect of office-based thyroid ultrasound on clinical decision making. Presentation at North Texas Chapter American College of Surgeons. Dallas, Texas, February 19, 1999.

An important diagnostic tool for the evaluation of thyroid disease, thyroid ultrasound has recently become available for use in surgical offices. The purpose of this report is to determine the lesional sensitivity of office-based thyroid ultrasound and its impact on clinical decision making. Surgical office-based thyroid ultrasound was performed on 49 consecutive patients who presented with thyroid disease. Indications for sonography included a solitary palpable nodule (n = 32), multiple palpable nodules (n = 3), diffuse enlargement (n = 5), or other hormonal or radiologic abnormalities (n = 9). Thyroid ultrasound demonstrated 104 lesions compared with 38 lesions found on physical examination (P < 0.0001). In the subpopulation who underwent scintigraphy (n = 10), 24 nodules were identified by ultrasound and only 10 nodules were identified by scan (P < 0.01). Overall, office-based thyroid ultrasound impacted the clinical management of 40 patients (80%): in 16 patients, thyroid ultrasound was the only modality that demonstrated a multinodular condition, thus contributing to a decision to avoid surgery; 19 patients had ultrasound-guided fine-needle aspiration of vaguely palpable or nonpalpable lesions; and 5 patients underwent ultrasoundguided cyst aspiration and follow-up. Office-based thyroid ultrasound performed by surgeons is a highly accurate imaging modality that identified significantly more lesions than physical examination or scintigraphy. Clinical management was affected through the identification of a multinodular process or through facilitation of accurate image-guided biopsy.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1317039/?tool=pubmed


Thyroid Nodule Sampling: Comparison of 22 Gauge versus 25 Gauge Needles. Oral Presentation North Texas Chapter American College of Surgeons, Feb 2007

Validation study of intraoperative fine-needle aspiration of parathyroid tissue with measurement of parathyroid hormone levels using the rapid intraoperative assay. BUMC Proceedings 2005; 18:214-216.

Surgical treatment of hyperparathyroidism relies on the ability to accurately identify parathyroid tissue. The use of intraoperative fine-needle aspiration (FNA) with measurement of intact parathyroid hormone level (iPTH-FNA) has been suggested as a useful adjunct and is evaluated in this pilot study.

An institutional review board–approved retrospective review was performed on patients undergoing parathyroid exploration for primary hyperparathyroidism who also underwent selective FNA at the end of the procedure. FNA was performed on excised parathyroid tissue, ipsilateral thyroid tissue, and muscle.

Ten patients underwent FNA. Mean iPTH-FNA values were 1559.6 pg/mL (range, 675–1775) for parathyroid, 51.4 pg/mL(range, 10–248) for thyroid, and 34.1 pg/mL (range, 14–128) for muscle. All iPTH-FNA assay results were significantly higher for parathyroid tissue than for either thyroid tissue (P < 0.05) or muscle (P < 0.05). There were no significant iPTH-FNA assay differences between thyroid and muscle (P = 0.09).
Intraoperative FNA of parathyroid tissue with the rapid iPTH assay can correctly identify parathyroid tissue. It may prove to be a useful surgical adjunct in the treatment of hyperparathyroidism.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200727/?tool=pubmed


Comparison of quick parathyroid assay for uniglandular and multiglandular parathyroid disease. Am J Surg 2002; 184:578-581.

The quick intraoperative parathyroid assay (qPTH) has been proposed as an effective tool in the surgical management of hyperparathyroidism. By measuring intact parathyroid hormone intraoperatively, the qPTH assay may facilitate directed exploration for solitary adenomas and may help guide the extent of resection in hyperplasia. In this study, results of the qPTH assay were analyzed prospectively in 63 consecutive patients who underwent exploration for hyperparathyroidism. Blood samples were drawn prior to surgical incision, prior to gland excision, and 5 and 10 minutes after gland excision. A decline ≥50% of the highest preincision or preexcision level within 10 minutes of resection was considered successful. Forty-nine patients (78%) had a solitary parathyroid adenoma. The qPTH assay was successful in 48 (98%) of these patients. One patient showed a delayed decline at 20 minutes. Fourteen patients (22%) had multiglandular disease: 6 with primary hyperplasia, 4 with hyperplasia secondary to renal failure, and 4 with double adenomas. The assay was successful in all of these patients. It detected multiglandular disease in 8 of 14 patients thought preoperatively to have solitary adenoma. Overall, the qPTH assay was successful in 62 of 63 patients (98%). All patients were normocalcemic after a median follow-up interval of 8 months. These data suggest that the qPTH assay can accurately facilitate directed neck exploration for solitary adenomas, guide the extent of resection for hyperplasia, and identify unknown multiglandular disease. It appears to eliminate the most common cause of parathyroidectomy failure, thereby improving surgical success rates while potentially decreasing morbidity, cost, and operative time.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276637/?tool=pubmed


Surgical Management of Thyroid Cancer Invading the Airway. Ann J Surg Oncol 1997; 4(5):403-8.

Locally advanced thyroid cancer invading the tracheal cartilage represents a difficult treatment dilemma during thyroidectomy. A retrospective chart review was performed to determine the results of laryngotracheal resection or tracheal cartilage shave with adjuvant radiotherapy in patients with locally advanced thyroid cancer invading the upper airway.

Of 597 patients undergoing thyroidectomy for thyroid cancer, 40 were found to have laryngotracheal invasion. Thirty-five patients with superficial invasion underwent cartilage shave procedures with adjuvant radiotherapy; five with full-thickness invasion underwent radical resection, including tracheal sleeve resection (n = 3) or total laryngectomy (n = 2). Histologic subtypes included papillary (n = 32), follicular (n = 2), Hurthle cell (n = 1), medullary (n = 3), and anaplastic (n = 2). Of the cartilage shave group, 25 are currently alive with no evidence of disease at a mean follow-up of 81 months (range 1-290). Six developed isolated local/regional recurrence and were managed with total laryngectomy (n = 1), tracheal resection (n = 1), cervical lymphadenectomy (n = 1), or repeat radiotherapy (n = 3). All six patients remain free of disease at a mean follow-up of 5 years. Of those who underwent initial laryngotracheal resection, four remain free of disease at a mean follow-up of 5 years. The rates of 10-year disease-free survival and overall survival for all patients were 47.9% (95% confidence interval [CI] 24.8, 71.0) and 83.9% (95% CI 70.3, 97.5), respectively.

These data suggest that adequate management of thyroid cancer with laryngotracheal invasion can be achieved with a more conservative surgical approach and adjuvant radiotherapy, reserving more radical resections for extensive primary lesions or locally recurrent disease.

http://www.ncbi.nlm.nih.gov/pubmed/9259967

Esophagus/Stomach

Sentinel lymph node biopsy for early gastric cancer. Poster Presentation at North Texas Chapter American Coll of Surgeons, February 2000.

Anastomotic integrity following esophagectomy for carcinoma: are histologically positive margins a risk factor for leak? North Texas Chapter American College of Surgeons, Feb 2002; Southwestern Surgical Congress, April 2002.

Laparoscopic Esophagectomy. Oral Presentation North Texas Chapter American College of Surgeons, Feb 2007.

Endoscopic Treatment of Early Esophageal Cancer. Oral Presentation, North Texas Chapter American College of Surgeons, February 2009.

Esophageal Mucosal Resection versus Simple Biopsy for Dysplasia. Oral Presentation, North Texas Chapter American College of Surgeons, February 2009.

Surgical management of esophageal carcinoma. BUMC Proceedings 2003; 16:280-4.
Although esophageal carcinoma is not the most common tumor—it accounts for only 5% of all gastrointestinal tumors and 1% of all new tumors—it has nearly a 1:1 mortality ratio: each year there are 14,000 new cases and 13,000 related deaths in the USA. Men have esophageal carcinoma 3 to 5 times more often than women, and black men are 3 times more likely than white men to have the disease. The mean age at diagnosis is 60 years. Other Sections▼
CKGROUND
Adenocarcinoma, typically in the distal third of the esophagus, and squamous cell carcinoma, typically in the proximal two thirds of the esophagus, each make up 49% of cases of esophageal cancer. The remaining cancers in this area include sarcoma (1%), lymphoma (0.5%), cylindroma (0.25%), and primary melanoma (0.25%) (1). The incidence of adenocarcinoma is clearly increasing; it will soon become the most prevalent type of cancer of the esophagus. No malignant tumor in the past 25 years has increased in incidence as much as adenocarcinoma of the esophagus. The primary risk of adenocarcinoma is related to the duration and severity of gastricesophageal reflux and the progression of mucosal changes from Barrett’s esophagus to dysplasia to adenocarcinoma. Early detection is the most important factor in determining survival. Most patients present with stage IIB to stage IV disease, and most disease occurs at the gastroesophageal junction.
Among patients with Barrett’s esophagus, the risk of developing adenocarcinoma is 0.2% to 2.1% each year; 77% of patients with adenocarcinoma have had Barrett’s esophagus. Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma, since it could miss adenocarcinoma located somewhere else in that region. Forty percent of patients with Barrett’s esophagus and dysplasia have invasive carcinoma in the resected specimen.
The incidence of squamous cell carcinoma, which used to be the major cause of esophageal cancer, has significantly decreased. The decrease may be related to reductions in risk factors, which include smoking, excessive alcohol use, caustic lye injury or thermal injury, diet, obesity, achalasia, and tylosis.
Typical symptoms of esophageal cancer include difficulty swallowing, with a feeling of fullness, pressure, burning, or coughing; a feeling of both liquids and solids becoming stuck behind the sternum; indigestion; emesis; and weight loss. Many patients attribute their symptoms to heartburn and do not seek the medical care they need.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200781/?tool=pubmed

Colon Cancer

CEA expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y anti-CEA monoclonal antibody.
We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 µCi of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.

Antibody, Immuno, Radiopharm 3:50, 1990.
http://cancerres.aacrjournals.org/content/51/14/3802.long

Gamma interferon enhancement in vivo of carcinoembryonic antigen expression in human colon cancer xenografts. Proc AACR 31:237, 1990. Presented at American Association for Cancer Research, Washington, DC, May 1990.

Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with gamma-interferon (gamma IFN) at varying doses, frequencies, and periods of duration. CEA content (micrograms/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB, The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at gamma IFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 micrograms/g; 29% ID/g) compared to control animals (0.9 micrograms/g; 10% ID/g). The effects of gamma IFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum gamma IFN level. Therefore, we conclude that enhancement of in vivo CEA expression by gamma IFN may have clinical relevance for tumor imaging and therapy using radiolabeled monoclonal antibodies.
http://www.ncbi.nlm.nih.gov/pubmed/1599911

Gamma interferon as an enhancer of carcinoembryonic antigen in human colon cancer xenografts. J Nucl Med, 31:764, 1990.

Interferon enhancement of radioimmunotherapy for colon cancer in vivo. J Nucl Med, 31:850, 1990.

Enhancement of sequential radioimmunotherapy with gamma interferon. Antibody, Immuno, Radiopharm 4:31, 1991. Third Conference on Radioimmunodetection and Radioimmunotherapy for Colon Cancer, Princeton, NJ, November 1990.

Liver Tumors

Hepatic Cryosurgical Ablation. Presentation at Southwestern Surgical Congress, April 1997. Rancho Mirage, CA

Radiofrequency interstitial thermal ablation of hepatic tumors. Presentation at North Texas Chapter American College of Surgeons. Dallas, Texas, February 19, 1999.

The clinical impact of iron oxide MRI in the management of hepatic tumors and comparison to computed tomography. Presentation at North Texas Chapter American College of Surgeons. Dallas, Texas, February 19, 1999. Presented at Society of Surgical Oncology, March 1999.

The surgical management of hepatic tumors has traditionally relied on preoperative contrast-enhanced computed tomography (CECT) in combination with intraoperative ultrasonography (IOUS). Unfortunately, the ability to detect and characterize hepatic tumors by using CECT is limited, and IOUS frequently reveals additional disease that alters the operative approach. Recent advances in hepatic magnetic resonance imaging (MRI) may improve preoperative tumor detection and characterization; however, little is known about how MRI compares with CECT or about the clinical impact and cost considerations of liver MRI.
A retrospective chart review was performed to compare iron oxide (Feridex [Fe])-MRI with CECT in the preoperative imaging of hepatic neoplasms, as well as to determine the clinical impact and overall healthcare costs associated with Fe-MRI.
Of approximately 1000 patients who underwent abdominal MRI at a single institution during a 20-month period, 57 were identified who underwent Fe-MRI evaluation of the liver. Indications for imaging included suspected metastases (n = 43), an indeterminate hepatic mass (n = 9), or primary hepatic cancer (n = 5). Overall, Fe-MRI identified a total of 157 lesions (mean, 2.75 per patient; range, 0-14). CECT was performed in 50 patients, of whom 35 had primary or metastatic cancer. Fe-MRI identified more lesions than CT (n = 136 vs. 77; P = .016), and the average size of lesion detected by Fe-MRI was significantly smaller than that by CECT (2.5 vs. 3.4 cm; P = .018). Comparison of CECT and Fe-MRI findings with IOUS and pathological specimens showed a significant difference in sensitivity (MRI, 86%; CECT, 58%; P<.001), and IOUS changed the operative approach in only 5% of those imaged with Fe-MRI. Overall, Fe-MRI altered the clinical management in 67% of patients imaged (n = 38 of 57), which corresponded to an overall net cost savings of $108,368 ($1,901 per patient).
Fe-MRI is a powerful imaging technique, with greater hepatic tumor detection sensitivity than CECT. Moreover, it is an economically feasible imaging method that will alter the clinical management in most patients imaged. http://www.ncbi.nlm.nih.gov/pubmed/10560856

The Role of Hepatic Artery Infusion Chemotherapy in Metastatic Colorectal Cancer. Poster Presentation North Texas Chapter American College of Surgeons, Dallas, TX Feb 2006.

Comparison of Stapled vs Non-stapled Hepatic Transection During Lobectomy. Poster Presentation North Texas Chapter American College of Surgeons Feb 2006.

Circulating Tumor Cells in Patients Undergoing Surgery for Hepatic Metastases from Colorectal Cancer. Oral Presentation North Texas Chapter American College of Surgeons, Feb 2007.
Circulating tumor cells (CTCs) have been detected in patients with a variety of metastatic cancers, including colorectal, and may be a significant prognostic variable in patients with liver metastases. This prospective study involved 20 patients (13 men and 7 women) undergoing surgical excision or ablation of liver metastases from a colon or rectal primary tumor. Four 7.5-mL vials of peripheral blood were drawn preoperatively, 2 weeks postoperatively, and during mobilization of the liver or at the beginning of radiofrequency ablation. The samples were centrifuged, the sera combined to a final volume of 7.5 mL, and the CellSearch system used to identify circulating epithelial cells. A CTC count >2 was defined as clinically significant. Preoperative CTC levels averaged 3.9 (range, 0–56) and were significant in 2 patients (10%). Postoperative CTC levels averaged 1.0 (in 18 patients; range, 0–9) and were significant in 1 patient (5%). Intraoperative CTC levels averaged 28.2 (range, 0–315) and were significant in 10 patients (50%). At a median follow-up of 11.5 months (range, 5–25), 6 patients (30%) were dead of disease, 6 patients (30%) showed no evidence of disease, and 8 patients (40%) were alive with disease. Statistical analysis suggested a correlation between the presence of postoperative CTCs and survival (P = 0.036), as well as with disease-free survival (P = 0.036). Thus, CTCs are present and quantifiable in many patients with colorectal hepatic metastases, and peripheral CTCs are present in greater quantity during intraoperative liver manipulation. This preliminary study suggests a relationship between the presence of postoperative CTCs and outcome. Further accrual and follow-up of this group is needed to confirm these findings.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804487/?tool=pubmed

Microwave ablation of larger and perivascular hepatic tumors. Oral Presentation North Texas Chapter American College of Surgeons, Feb 2011.

Furin-inhibition and GM-CSF vaccine for colorectal liver metastases: a case study. Oral presentation, North Texas Chapter American College of Surgeons, Feb 2011

Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. BUMC Proceedings 2010;23:11-14.
Circulating tumor cells (CTCs) have been detected in patients with a variety of metastatic cancers, including colorectal, and may be a significant prognostic variable in patients with liver metastases. This prospective study involved 20 patients (13 men and 7 women) undergoing surgical excision or ablation of liver metastases from a colon or rectal primary tumor. Four 7.5-mL vials of peripheral blood were drawn preoperatively, 2 weeks postoperatively, and during mobilization of the liver or at the beginning of radiofrequency ablation. The samples were centrifuged, the sera combined to a final volume of 7.5 mL, and the CellSearch system used to identify circulating epithelial cells. A CTC count >2 was defined as clinically significant. Preoperative CTC levels averaged 3.9 (range, 0–56) and were significant in 2 patients (10%). Postoperative CTC levels averaged 1.0 (in 18 patients; range, 0–9) and were significant in 1 patient (5%). Intraoperative CTC levels averaged 28.2 (range, 0–315) and were significant in 10 patients (50%). At a median follow-up of 11.5 months (range, 5–25), 6 patients (30%) were dead of disease, 6 patients (30%) showed no evidence of disease, and 8 patients (40%) were alive with disease. Statistical analysis suggested a correlation between the presence of postoperative CTCs and survival (P = 0.036), as well as with disease-free survival (P = 0.036). Thus, CTCs are present and quantifiable in many patients with colorectal hepatic metastases, and peripheral CTCs are present in greater quantity during intraoperative liver manipulation. This preliminary study suggests a relationship between the presence of postoperative CTCs and outcome. Further accrual and follow-up of this group is needed to confirm these findings.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804487/?tool=pubmed

The clinical impact of iron oxide MRI in the management of hepatic tumors and comparison to computed tomography. Ann Surg Onc. 1999; 6:691-698.

The surgical management of hepatic tumors has traditionally relied on preoperative contrast-enhanced computed tomography (CECT) in combination with intraoperative ultrasonography (IOUS). Unfortunately, the ability to detect and characterize hepatic tumors by using CECT is limited, and IOUS frequently reveals additional disease that alters the operative approach. Recent advances in hepatic magnetic resonance imaging (MRI) may improve preoperative tumor detection and characterization; however, little is known about how MRI compares with CECT or about the clinical impact and cost considerations of liver MRI.
A retrospective chart review was performed to compare iron oxide (Feridex [Fe])-MRI with CECT in the preoperative imaging of hepatic neoplasms, as well as to determine the clinical impact and overall healthcare costs associated with Fe-MRI.
Of approximately 1000 patients who underwent abdominal MRI at a single institution during a 20-month period, 57 were identified who underwent Fe-MRI evaluation of the liver. Indications for imaging included suspected metastases (n = 43), an indeterminate hepatic mass (n = 9), or primary hepatic cancer (n = 5). Overall, Fe-MRI identified a total of 157 lesions (mean, 2.75 per patient; range, 0-14). CECT was performed in 50 patients, of whom 35 had primary or metastatic cancer. Fe-MRI identified more lesions than CT (n = 136 vs. 77; P = .016), and the average size of lesion detected by Fe-MRI was significantly smaller than that by CECT (2.5 vs. 3.4 cm; P = .018). Comparison of CECT and Fe-MRI findings with IOUS and pathological specimens showed a significant difference in sensitivity (MRI, 86%; CECT, 58%; P<.001), and IOUS changed the operative approach in only 5% of those imaged with Fe-MRI. Overall, Fe-MRI altered the clinical management in 67% of patients imaged (n = 38 of 57), which corresponded to an overall net cost savings of $108,368 ($1,901 per patient).
Fe-MRI is a powerful imaging technique, with greater hepatic tumor detection sensitivity than CECT. Moreover, it is an economically feasible imaging method that will alter the clinical management in most patients imaged.
http://www.ncbi.nlm.nih.gov/pubmed/10560856

Cryosurgical ablation of colorectal metastasis to the liver. BUMC Proceedings 1994; 7:3-7.

Gamma interferon enhancement of a multiple treatment regimen for radioimmunotherapy. Antibody, Immuno, Radiopharm 1991; 4:837-845.

Interferon enhancement of radioimmunotherapy for colon carcinoma. Cancer Res. 1991 May 1;51(9):2335-9.
Recombinant human γ-interferon (IFN-γ) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of γ-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen 90Y-MAb (ZCE025, 120 µCi) plus IFN-γ (61.8 days) as compared to animals that received specific 90Y-MAb with phosphate-buffered saline (34.9 days; P < 0.005). IFN-γ (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after 90Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific 90Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-γ. The difference was more apparent when compared to animals receiving IFN-γ alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P < 0.001). Increased antibody localization in the tumors of animals treated with IFN-γ plus specific 90Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific 90Y-MAb without IFN-γ (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific 90Y-MAb with IFN-γ (2477 cGy) compared to animals treated without IFN-γ (1217 cGy). These results provide support for the use of γ-interferon as an immunomodulating agent prior to radioimmunotherapy.
http://cancerres.aacrjournals.org/content/51/9/2335.long

Monoclonal antibodies and colorectal carcinoma. Cancer Investigation 1994; 12:314-323. http://www.ncbi.nlm.nih.gov/pubmed/8187009

Gamma interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts. J Immunotherapy 1992; 11:257-266.

Intraoperative gamma detection probe with presurgical antibody imaging for colon cancer Arch of Surg 1991; 126:1398-1403.

In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In-MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In-MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In-MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake.
http://www.ncbi.nlm.nih.gov/pubmed/1747053

Screening for hepatocellular carcinoma in the multinodular, cirrhotic liver. Presented at North Texas Chapter American Coll of Surgeons, February 2000 and Society of Surgical Oncology, March, 2000

Long term results for cryosurgery after liver metastases from colorectal cancer. North Texas Chapter American College of Surgeons, Feb 2002, Best Oncology Paper.

Operative Probe Scintimetry With Indium and Technetium for Colorectal Cancer. J Surg Onc 2007; 96:290-96.

Surgeons introduced the hand-held gamma detection probe in combination with tumor-directed monoclonal antibodies in patients with colorectal cancer. The clinicians conducted innovative research involving antibody chemistry and variation as well as radioactive dosimetry and decay. The results of these studies represented an era when surgeons began reporting on specific lesion detection and the impact of the antibody administration on the management of the patient. The summary of the important early trials involving monoclonal antibodies and probe scintimetry provides a valuable look into the early development of the antibody technology and a glimpse of potential future applications using the gamma detection probe.
http://www.ncbi.nlm.nih.gov/pubmed/17879338

Hepatic imaging with iron oxide magnetic resonance imaging. Oncology (suppl) 2000; 14:29-36.
The management of hepatic tumors presents a challenging problem. The natural history of primary and metastatic liver lesions portends a poor prognosis. However, surgical resection and newer ablative techniques have had a great impact on cure rates. Unfortunately, the majority of newly diagnosed patients have surgically unresectable disease. Advances in hepatic imaging have improved the preoperative evaluation of malignant lesions and greatly assisted in selecting patients for surgical resection or other interventions. Currently, a number of modalities are available for the evaluation of hepatic tumors. This article provides an overview of some of the modalities currently in use, examines the role of iron oxide magnetic resonance imaging (MRI), and relates experience with its use at Baylor University Medical Center. http://www.ncbi.nlm.nih.gov/pubmed/10887649

Diagnostic evaluation of hepatocellular carcinoma in a cirrhotic liver. Oncology (suppl) 2000; 14:15-20. http://www.ncbi.nlm.nih.gov/pubmed/10887647

Hepatic cryosurgery. Oncology 1998; 12:979-98.
The curative management of primary and metastatic liver tumors has traditionally relied on surgical resection. Unfortunately, fewer than 10% of newly diagnosed patients have tumors that are considered to be surgically resectable. Limitations that often preclude a safe surgical resection include bilobar or centrally located tumors, insufficient hepatic reserve, cirrhosis, and/or associated comorbid medical conditions. For individuals with unresectable hepatic tumors, the treatment options are few, and the prognosis is uniformly poor. However, cryosurgery is a promising therapeutic alternative for these patients. This rapidly emerging technology allows for image-guided in situ tumor eradication using subzero temperatures, while selectively sparing most normal hepatic tissue. Tumor death occurs by direct cellular freezing and indirectly through vascular thrombosis and tissue anoxia. Accumulating data suggest that cryosurgery is a safe, effective treatment option for patients who would otherwise fair quite poorly, and that it may achieve long-term survival rates similar to those observed with formal surgical resection. This article summarizes the role cryosurgery may play in the management of patients with surgically unresectable primary and metastatic liver tumors.
http://www.ncbi.nlm.nih.gov/pubmed/9684270

Cryosurgical ablation of hepatic tumors. Am J Surg 1997; 174:614-618.
Cryosurgical ablation of hepatic tumors relies on nonspecific tissue necrosis due to freezing as well as microvascular thrombosis. Patients with selected primary and metastatic hepatic malignancies who are not candidates for surgical resection are afforded potentially curative benefit using this technique.
Forty patients underwent cryosurgery for hepatic malignancy related to colorectal metastasis (n = 27), hepatocellular carcinoma (n = 8), metastatic breast (n = 2), metastatic neuroendocrine (n = 2), and metastatic ovarian carcinoma (n = 1). Intraoperative ultrasound (IOUS) was used in all patients to help locate the tumor and guide the cryosurgical trocar to the lesions.
Indications for cryosurgical ablation included bilobar and centrally located disease, poor medical risk, insufficient hepatic reserve, and involved margin after wedge resection. Major complications included hepatic parenchyma cracking requiring transfusion in 5 patients, 1 postoperative biliary stenosis, and 1 inferior vena cava injury. There were 3 postoperative deaths from non-hepatic-related events. Based on Kaplan-Meier analysis the estimated overall survival for patients with hepatocellular carcinoma (60% at 18 months) was compared with patients with colorectal metastases (30% at 18 months). Nine patients (23%) are currently free of disease with an average follow-up of 17.7 months. The pattern of failure was identified at the site of cryosurgical ablation in 2 of 88 lesions.
Cryosurgical ablation of selected hepatic malignancies is a safe and viable treatment for patients not amenable to surgical resection.
http://www.ncbi.nlm.nih.gov/pubmed/9409584

Pancreas

Surgical experience with neuroendocrine tumors of the pancreas. Presented at North Texas Chapter American Coll of Surgeons, February 2000 and Southwestern Surgical Congress April 2000.

Does Intraoperative Suspicion of Portal Vein Invasion Preclude resection of Peripancreatic Carcinoma. Poster presentation Society of Surgical Oncology, March 1997.

Laparoscopic Lateral Roux-en-Y Pancreaticojejunostomy: A Case Series. Oral Presentation, North Texas Chapter American College of Surgeons, February 2009.

TNFerade, an adenovector carrying the transgene for human tumor necrosis factor a, for patients with advanced solid tumors: surgical experience and long-term follow-up. Ann Surg Onc, 2005; 12:825-30.
Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-alpha to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-alpha. The recent focus has been on developing a local delivery system for TNF-alpha to minimize the systemic response.
This study was part of a phase I open-label multi-institutional trial using TNFerade. We focus on the patients treated at Baylor University Medical Center and provide postoperative and long-term follow-up. TNFerade uses a second-generation nonreplicating adenovirus as the vector for delivery of the human transgene TNF-alpha. An early growth response 1 promoter was placed upstream from the TNF-alpha gene. This promoter is activated by ionizing radiation, thus allowing for temporal and spatial control of TNF-alpha release. Tumors were injected over 5 weeks with ionizing radiation given 3 days after injections for 6 weeks. Tumor response was measured by computed tomographic imaging and physical examination.
As described in our original experience, no patients experienced dose-limiting toxicities up to doses of 4 x 10(11) particles per injection. Tumors injected demonstrated a response independently of histology. Four patients had complete regression of the tumor injected. Three patients with complete regression have survived > or = 2 years from the time of treatment.
Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials.http://www.ncbi.nlm.nih.gov/pubmed/16132372

Surgical morbidity, mortality, and long term survival in patients with peripancreatic cancer following pancreaticoduodenectomy. Am J Surg 1997; 174:600-604.

Association of an abnormal pancreaticobiliary junction with biliary tract cancers. BUMC Proceedings 2000; 13:11-13.
Recent international reports have suggested that an abnormal pancreatic and bile duct junction can influence the degree of pancreatic fluid regurgitation, resulting in an increased incidence of biliary tract malignancy. To confirm these reports, we retrospectively examined the anatomic relation at the pancreaticobiliary junction in all patients diagnosed with cholangiocarcinoma or gallbladder cancer at Baylor University Medical Center (BUMC) over a 10-year period. From 1989 to 1998, 82 patients with bile duct cancer were treated at BUMC. Adequate visualization of the pancreaticobiliary junction was accomplished in 29 patients (35%). Among these patients, an abnormal junction, with a common channel length of 8 to >15 mm, was noted in 13 patients (45%). Thus, this study confirms previous reports regarding the high incidence of an abnormal pancreaticobiliary junction in patients with bile duct cancer. A prospective effort to examine this anatomy and the length of the common channel should be encouraged to identify a potential high-risk group. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312207/?tool=pubmed

Neuroendocrine Tumors of the Pancreas. Curr Treat Options Gastroenterol. 2004 Oct;7(5):355-364.
Neuroendocrine tumors (NETs) are rare tumors of the endocrine pancreas that require a high degree of suspicion for timely diagnosis. Diagnosis is often delayed due to the nonspecific and intermittent presentation of symptoms. As many as 45% to 55% of tumors are nonfunctional and are typically diagnosed secondary to mass effect related symptoms or found incidentally. Functional tumors often are symptom specific and are diagnosed at an earlier stage than nonfunctional tumors. The challenging aspects of treating NETs are localizing the tumors, treating extensive or metastatic disease, and palliating symptoms. Most NETs have an indolent course, and aggressive multimodality treatment is often indicated and encouraged.http://www.ncbi.nlm.nih.gov/pubmed/15345206

Peritoneal Cancer

Oxaliplatin compared to mitomycin C for hyperthermic intraperitoneal chemotherapy. Poster Presentation North Texas Chapter American College of Surgeons, Feb 2011.

Intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis: analysis and outcomes. Oral presentation Feb 2004 North Texas Chapter ACS Meeting.

Pseudomyxoma Peritonei and Intraperitoneal Hyperthermic Chemotherapy. Poster Presentation North Texas Chapter American College of Surgeons, Dallas, Tx Feb 25, 2005, Poster Presentation Southwest Surgical Congress

Gauze protection of outflow catheters during hyperthermic perfusion. Poster Presentation, North Texas Chapter American College of Surgeons, Feb 2011.

Intraoperative modality of treatment for peritoneal carcinomatosis: use of hyperthermic intraperitoneal chemoperfusion. Perfusion 2002; 17:441-6.

The use of hyperthermia as an adjunct to chemotherapy in the treatment of peritoneal carcinomatosis is a promising technique for patients who otherwise have a poor prognosis for survival. We, herein, report an overview and description of our technique for the safe conduct of this treatment. Included in these data are a total of 71 patients who underwent an intraoperative treatment with Mitomycin C at temperatures of 41-42 degrees C for a 90- to 120-min time period. The treatment protocol, perfusion system description, technical considerations, and potential complications are also included. The prognosis for intraabdominal carcinomatosis is poor with conventional treatments and modalities. We believe that the use of this technique offers a very positive clinical alternative for patients undergoing treatment for laparoscopic palliation of malignant ascites and/or surgical debulking for intraoperative treatment and prevention of metastasis. http://www.ncbi.nlm.nih.gov/pubmed/12470035

Intraperitoneal hyperthermic chemotherapy: experience at Baylor University Medical Center. BUMC Proceedings 2002; 15:359-365. LINK>>>>>>>
Patients with peritoneal carcinomatosis have a dismal prognosis despite systemic chemotherapy or palliative surgery. A novel strategy of complete tumor debulking with intraoperative hyperthermia with chemotherapy has been proposed to provide prolonged survival.
To retrospectively analyze the preliminary experience with this technique at Baylor University Medical Center.
All patients underwent attempted tumor debulking followed by intraperitoneal hyperthermia with 40 mg mitomycin-C over 2 hours.
Patient diagnoses included nonmucinous colorectal carcinomatosis (n = 9), diffuse peritoneal adenomucinosis (n = 1), peritoneal mucinous carcinomatosis (n = 2), and gastric carcinomatosis (n = 3). Tumors in most patients (13/15) were resected to ≤5 mm, and those in 10 of 15 were resected to no gross disease. Complications included ileus (n = 9), bowel leak (n = 2), infection (n = 1), and fistula (n = 1). One patient died of progressive gastric cancer at 1 month. Within a median follow-up of 4 months, 8 patients had no tumor by radiologic or tumor marker analysis.
Intraoperative hyperthermia with chemotherapy is a viable treatment for patients with isolated peritoneal carcinomatosis from colorectal or gastric origin. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276636/?tool=pubmed

Melanoma

The need for completion lymph node dissection following positive sentinel lymph node biopsy for cutaneous melanoma. Presentation at North Texas Chapter American College of Surgeons. Dallas, Texas, February 19, 1999.

Completion lymph node dissection following positive sentinel lymph node biopsy for cutaneous melanoma. Presentation at Southwestern Surgical Congress, April 2000.

Loss of heterozygosity at 6q22-23.3 in congenital nevi, acquired nevi, and cutaneous melanoma after laser capture microdissection. Society of Surgical Oncology March 2002, North Texas Chaper American College of Surgeons, Feb 2002, Best Poster Award.

Patterns of recurrence following sentinel lymph node biopsy for melanoma. North Texas Chapter American College of Surgeons, Feb 2003 oral presentation, Southwestern Surgical Congress, April 2003, oral presentation.

Does a shave biopsy of cutaneous melanoma increase the risk of nodal or local recurrence? Oral presentation Feb 2004, North Texas Chapter ACS Meeting.

Circulating tumor cells in melanoma: a review of the literature and description of a novel technique. BUMC Proceedings 2008;21:127-132.
Melanoma is a prevalent and deadly disease with limited therapeutic options. Current prognostic factors are unable to adequately guide treatment. Circulating tumor cells are a disease-specific factor that can be used as a prognostic variable to guide therapy. Most research to date has focused on identification of circulating tumor cells using various methods, including polymerase chain reaction. These techniques, however, have poor sensitivity and variable specificity and predictive significance. A recently developed technology to identify circulating tumor cells is the CellSearch system. This system uses immunomagnetic cell labeling and digital microscopy. This technology may provide an alternative method to identify circulating tumor cells in patients with advanced-stage melanoma and function as a prognostic factor. We review the literature on circulating tumor cells in melanoma and present data collected at our institution using the CellSearch system in nine patients with stage III or IV melanoma. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277345/?tool=pubmed

Patterns of drainage and recurrence following sentinel lymph node biopsy for cutaneous wide local excision of cutaneous melanoma. Am J Surg 2002; 184:176-78.

Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy.
A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry.
One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively (P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence.
The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.
http://www.ncbi.nlm.nih.gov/pubmed/14672778

Patterns of drainage and recurrence following sentinel lymph node biopsy for cutaneous melanoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2004 Jul;130(7):844-8.
http://archotol.ama-assn.org/cgi/content/full/130/7/844

Sentinel lymph node biopsy site used as skin graft donor in melanoma of the head and neck. Arch Oto HNeck Surg 2004; 130:844-48.

Wound defects after wide local excision (WLE) for cutaneous melanoma can occasionally require the use of skin grafts for closure. Harvesting the skin graft can result in an additional wound.
The increasing use of sentinel lymph node (SLN) biopsy in cutaneous melanoma at our institution has facilitated the development of an alternative technique for obtaining donor skin. The proposed method utilizes the skin overlying the SLN as the skin graft donor site. Sixteen patients underwent WLE of intermediate to thick melanomas with SLN biopsy and full thickness skin graft harvested from the SLN biopsy site.
After a median follow-up of 12 months, there were no graft failures. There were 2 partial graft losses. There were no wound complications. There were no melanoma recurrences.
In cases where primary closure is not technically feasible or cosmetically favorable, the use of the SLN incision site as a skin graft donor provides the surgeon with an effective repair and spares the patient an additional skin graft donor site defect. http://www.ncbi.nlm.nih.gov/pubmed/12169366

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study. Melanoma Research 2001; 11:45-55.
Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.http://www.ncbi.nlm.nih.gov/pubmed/11254115

Malignant melanoma and the sentinel node biopsy. Cancer Invest 1999; 17:39-46.

Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma. Cancer Gene Therapy 1998; 5:292-300.

Sentinel lymph node biopsy for melanoma. Am J Surgery 1998; 176:544-547.
The most powerful predictor of survival for patients with melanoma is the status of the regional lymph nodes. Sentinel lymph node biopsy may provide improved staging accuracy without the morbidity of elective lymph node dissection (ELND).
Sixty-eight patients with intermediate thickness melanoma underwent gamma probe guided sentinel node biopsy without ELND and were followed up over a mean of 22 months.
A sentinel node was found in all patients. Six patients (9%) had positive sentinel nodes; all underwent complete lymphadenectomy. Two patients (3%) with negative sentinel nodes developed nodal recurrence; 1 of these patients was found to have microscopic disease on reexamination of the sentinel node. Two patients (3%) developed systemic disease.
Gamma probe guided sentinel node biopsy can be performed with a high rate of technical success. It provides accurate pathological staging with a low incidence of nodal basin failure.http://www.ncbi.nlm.nih.gov/pubmed/9926787

The sentinel node in breast cancer: a multicenter validation study. N Eng J Med 1998; 339:941-946.
Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings.
We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. “Hot spots” representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy.
The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status of the axillary nodes was 97 percent (392 of 405); the specificity of the method was 100 percent, the positive predictive value was 100 percent, the negative predictive value was 96 percent (291 of 304), and the sensitivity was 89 percent (101 of 114). The sentinel nodes were outside the axilla in 8 percent of cases and outside of level 1 nodes in 11 percent of cases. Three percent of positive sentinel nodes were in nonaxillary locations.
CONCLUSIONS
Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient.http://www.nejm.org/doi/full/10.1056/NEJM199810013391401

Localization of regional lymph nodes in melanomas of the head and neck. Arch Oto Head Neck Surg 1998; 124:135-140.
http://archotol.ama-assn.org/cgi/pmidlookup?view=long&pmid=9485103

Phase I trial of retroviral vector-mediated gamma-interferon gene transfer into autologous tumor cells in patients with metastatic melanoma. Cancer Gene Ther 1998; 5(5):292-300.
The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.http://www.ncbi.nlm.nih.gov/pubmed/9824048

Malignant melanoma and the sentinel lymph node biopsy. Cancer Invest 1999; 17(1):39-46.

Breast Cancer

The significance of micrometastasis in the sentinel lymph node for breast cancer. Presented at North Texas Chapter American Coll of Surgeons, February 2000 and Southwestern Surgical Congress April 2000 (best poster award)

Phase II results with sentinel lymphadenectomy for breast cancer staging. Presented at North Texas Chapter American Coll of Surgeons, February 2000.

Failed breast sentinel lymphadenectomy: interaction of patient age, body mass index, and tumor location. American Society of Breast Surgeons, May 2000.

Current patterns of presentation and treatment of breast cancer in women 40 years of age or less. North Texas Chapter American College of Surgeons, Feb 2003, oral presentation.

Periareolar fine needle aspiration cytology for breast cancer prediction: technical results. North Texas Chapter American College of Surgeons, Feb 2001, Southwestern Surgical Congress, April 2001.

Circulation tumor cells in patients undergoing surgery for primary breast cancer: preliminary results of a pilot study. Ann Surg Oncol. 2009:969-71.
Circulating tumor cells (CTCs) have recently been shown to be an independent predictor of progression-free and overall survival in patients undergoing treatment for metastatic breast cancer. This study evaluates the presence and significance of CTCs in patient undergoing surgical resection of clinically localized primary breast cancer.
Patients undergoing surgery for clinically localized primary breast cancer were enrolled into a prospective study. Thirty milliliters of blood was drawn and studied using the CellSearch assay.
Forty-one patients were enrolled at a single tertiary referral center. Ten patients (24.4%) had detectable CTCs preoperatively (PreOp). Nine (30%) patients were found to have CTCs postoperatively (PostOp). Overall, 16 (39%) were found to have CTCs either PreOp or PostOp. Hormone-negative patients were significantly more likely to have CTCs than hormone-positive patients. No other pathologic factor was predictive of the presence of CTCs.
CTCs are detectable and quantifiable in breast surgery patients. CTCs were more likely to be found in hormone receptor negative patients. Further study will allow correlation with other pathological variables and clinical outcome.http://www.ncbi.nlm.nih.gov/pubmed/19190965

Survival analysis following sentinel lymph node biopsy: a validation trial demonstrating the accuracy of staging early breast cancer. BUMC Proceedings 2005; 18: 102-7. Few long-term follow-up studies prove sentinel lymph node biopsy (SLNB) effectively stages breast cancer without the further evaluation of a completion axillary dissection. Our prospective study addressed this issue, enrolling 345 women with clinically node-negative breast cancer who underwent SLNB from October 1997 through December 2000. The median age of the patients in the study was 56.7 years. Average primary tumor size was 1.42 cm. Ninety-three patients had a positive sentinel lymph node (27%); 70 (75.3%) of these patients underwent completion axillary dissection, while 23 patients (24.7%) declined further surgery. Most (91.3%) of the patients who declined further surgery had evidence of micrometastatic disease only. The median follow-up period for all patients was 60 months. No tumor recurrences in the axilla were reported in either sentinel node-negative or -positive patients. The local and systemic recurrence rates were 3.1% and 4% in node-negative patients and 2.2% and 4.3% in node-positive patients. Two patients (0.9%) in the node-negative group and 6 (6.5%) in the node-positive group died of their disease. Estimated 5-year disease-free survival rates were 96% for node-negative patients and 87% for node-positive patients (P = 0.02). The clinical false-negative rate of the SLNB in this study was 0%. This long-term validation trial proves the accuracy of the SLNB and its extremely low false-negative rate. The findings indicate that patients with a positive SLNB have significantly different survival rates than patients with a negative SLNB. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200707/?tool=pubmed

Brady BM, Fant J, Jones RC, Grant MD, McCarty TM, Livingston SA, Kuhn JA. Sentinel lymph node biopsy followed by delayed mastectomy and reconstruction. Am J Surg 2003; 185:114-17.
The role of sentinel lymph node (SLN) biopsy with total mastectomy is evolving. In patients who desire mastectomy with immediate reconstruction, the final pathologic results of the SLN may create unique problems. Specifically, if the SLN is found to be positive on final pathology, the reconstructed patient would generally require a potentially difficult re-operation on the remaining axillary nodes. The purpose of this study was to review the results of patients who underwent an initial SNL biopsy followed by a planned mastectomy and reconstruction.
A chart review of patients who underwent staged SLN biopsy with subsequent definitive procedure between 1997 and 2001 was conducted. These were evaluated with regard to type of tumor, status of sentinel node, and design of subsequent operation.
There were 40 patients who underwent an initial SLN biopsy followed by a staged mastectomy with reconstruction. Tumors included high-grade carcinoma in situ (n = 4), infiltrating ductal carcinoma (n = 28), invasive lobular carcinoma (n = 4), mucinous carcinoma (n = 1), adenoid cystic carcinoma (n = 1), and mixed ductal and lobular carcinoma (n = 2). Tissue biopsy was obtained by either open (n = 9) or needle (n = 31) technique. Twenty-five patients had a negative SLN biopsy and a delayed total mastectomy with immediate reconstruction. Positive SLNs were identified in 15 patients (37%). Eight patients had macroscopic nodal metastases and underwent a delayed modified radical mastectomy and immediate reconstruction. Seven patients had microscopic nodal metastases and 3 declined further axillary dissection. They proceeded with total mastectomy and immediate reconstruction.
These data suggest that a substantial proportion of patients treated with SLN biopsy, simple mastectomy, and reconstruction will have positive sentinel lymph nodes. Thus, the ideal approach for patients who wish to have reconstruction should involve an initial SLN biopsy as a separate procedure. If the SLN is benign, the patient may undergo a total mastectomy with immediate reconstruction. However, a patient with a positive SLN may proceed to a modified radical mastectomy with immediate reconstruction. This treatment algorithm eliminates a potentially difficult reoperation on the axilla following reconstruction.http://www.ncbi.nlm.nih.gov/pubmed/12559439

Preliminary outcome analysis in patients with breast cancer and a positive sentinel lymph node who declined axillary dissection. Ann Surg Onc 2003; 10:126-130

This retrospective study was designed to provide a preliminary outcome analysis in patients with positive sentinel nodes who declined axillary dissection.
A review was conducted of patients who underwent lumpectomy and sentinel lymph node excision for invasive disease between January 1998 and July 2000. Those who were found to have sentinel lymph node metastasis without completion axillary dissection were selected for evaluation. Follow-up included physical examination and mammography.
Thirty-one patients were identified who met inclusion criteria. Primary invasive cell types included infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mixed cellularity. Most primary tumors were T1. Nodal metastases were identified by hematoxylin and eosin stain and immunohistochemistry. Twenty-seven of the metastases were microscopic (<2 mm), and the remaining four were macroscopic. All patients received adjuvant systemic therapy. With a mean follow-up of 30 months, there have been no patients with axillary recurrence on physical examination or mammographic evaluation.
We have presented patients with sentinel lymph nodes involved by cancer who did not undergo further axillary resection and remain free of disease at least 1 year later. This preliminary analysis supports the inclusion of patients with subclinical axillary disease in trials that randomize to observation alone.
http://www.ncbi.nlm.nih.gov/pubmed/12620906

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node. BUMC Proceedings 2003; 16:3-6. Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size <2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and im-munohistochemistry. The median age of these 24 patients was 52 years (range, 34–83). Their primary tumor stages were T,a andT,b (n = 5), T,c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micro-metastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200802/?tool=pubmed

Gene Therapy

Therapeutic aspects of oncogene determination. BUMC Proceedings 7:26, 1994.

Tumor Harvesting for Vaccine Development: Predictors of Optimal Outcome. Oral Presentation, North Texas Chapter American College of Surgeons, Februray 2009.

Phase I trial of TGF-beta2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin Cncer Res. 2011 Jan1;17(1):183-92..

On the basis of the hypothesis that the combined expression of immunostimulatory granulocyte macrophage colony stimulating factor (GM-CSF) and antitumor suppressor TGF-β2 antisense (AS) transgenes can break tolerance and stimulate immune responses to cancer-associated antigens, we constructed an expression plasmid [the tumor-associated glycoprotein (TAG) plasmid] that coexpresses GM-CSF and TGF-β2 AS nucleotide sequences and which was incorporated into an autologous whole-cell vaccine.
Patients undergoing resection were enrolled. Freshly harvested autologous tumor cells were mechanically and enzymatically disaggregated, then electroporated with the TAG vector. The resulting vaccine was irradiated, then aliquoted and cryopreserved until the time of injection. Patients received a minimum of 5 to a maximum of 12 monthly intradermal injections. Immune function was monitored at baseline and at months 3 and 6.
Vaccine manufacturing efficiency was 84% (32/38). Twenty-three patients received at least 1 vaccination. There were no grade 3 or 4 toxicities, and grade 1 and 2 events were local in nature. Seventeen of 21 patients had stable disease (SD) at month 2 or later as their best response, and 1 patient with stage IVa malignant melanoma achieved a complete response (CR) following 11 vaccinations and remains without evidence of disease 2 years following initiation of therapy. Six of 13 patients displayed a positive enzyme-linked immunospot (ELISPOT) response to autologous TAG vaccine at week 12 including 3 patients with prolonged SD or CR. The 3 other patients survived through week 24, as compared with none of the 7 ELISPOT-negative patients.
On the basis of safety and clinical and immunologic results, further evaluation of bifunctional vaccines is warranted.http://www.ncbi.nlm.nih.gov/pubmed/21208907

Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther. 2010:780-91.
RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in this regard. We developed a novel ‘bifunctional’ RNAi strategy, which further optimizes target gene knockdown outcome. A bifunctional construct (bi-sh-STMN1) was generated against Stathmin1, a critical tubulin modulator that is overexpressed in human cancers. The bifunctional construct is postulated to concurrently repress the translation of the target mRNA (cleavage-independent, mRNA sequestration and degradation) and degrade (through RNase H-like cleavage) post-transcriptional mRNA through cleavage-dependent activities. Bi-sh-STMN1 showed enhanced potency and durability in parallel comparisons with conventional shRNA and siRNAs targeting the same sequence. Enhanced STMN1 protein knockdown by bi-sh-STMN1 was accompanied by target site cleavage at the mRNA level showed by the rapid amplification of complementary DNA ends (RACE) assay. Bi-sh-STMN1 also showed knockdown kinetics at the mRNA level consistent with its multieffector silencing mechanisms. The bifunctional shRNA is a highly effective and advantageous approach mediating RNAi at concentrations significantly lower than conventional shRNA or siRNA. These results support further evaluations.http://www.ncbi.nlm.nih.gov/pubmed/20596090

Hereditary inclusion body myopathy: single patient response to GNE gene lipoplex therapy. J Gene Med. 2010:403-12.
Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult onset myopathy. It is characterized by mutations of the GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene. Afflicted patients have no therapeutic options. In preclinical testing, we have previously demonstrated the ability to correct GNE gene function and the safety of delivery of wild type GNE gene using a liposomal delivery vehicle.
A single patient (subject #001) with severe HIBM treated by compassionate investigational new drug received four doses of GNE gene Lipoplex via intramuscular injection. GNE transgene expression, downstream induction of sialic acid, safety and muscle function were evaluated.
Significant durable improvement in locoregional skeletal muscle function was observed in the injected left extensor carpi radialis longus of #001 in correlation with GNE transgene upregulation and local induction of sialic acid. Other than transient low grade fever and pain at the injection site, no significant toxicity was observed.
Proof of principle for manufacturing of ‘clinical grade’ GNE gene Lipoplex, clinical safety and activity are demonstrated with GNE gene Lipoplex. Further assessment will involve intravenous administration and subsequent phase I trial involving additional but less severely afflicted HIBM patients.http://www.ncbi.nlm.nih.gov/pubmed/20440751

Hereditary inclusion body myopathy: single patient respons to GNE gene Lipoplex therapy. J Gene Med. 2010 12:403-12.
Abstract Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult-onset myopathy due to mutations in the GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene. Affected patients have no therapeutic options. We have previously demonstrated in preclinical testing the ability to safely correct GNE gene function through liposomal delivery of the wild-type GNE gene. Results were verified in a single patient treated by intravenous infusion of GNE gene lipoplex. A single patient (patient 001) with severe HIBM treated with a compassionate investigational new drug received seven doses of GNE gene lipoplex via intravenous infusion at the following doses: 0.4, 0.4, 1.0, 4.0, 5.0, 6.0, and 7.0 mg of DNA. GNE transgene expression, downstream induction of sialic acid, safety, and muscle function were evaluated. Transient low-grade fever, myalgia, tachycardia, transaminase elevation, hyponatremia, and hypotension were observed after infusion of each dose of GNE gene lipoplex. Quadriceps muscle expression of the delivered GNE, plasmid, and RNA was observed 24 hr after the 5.0-mg dose and at significantly greater levels 72 hr after the 7.0-mg infusion in comparison with expression in quadriceps muscle immediately before infusion. Sialic acid-related proteins were increased and stabilization in the decline of muscle strength was observed. We conclude that clinical safety and activity have been demonstrated with intravenous infusion of GNE gene lipoplex. Further assessment will involve a phase I trial of intravenous administration of GNE gene lipoplex in individuals with less advanced HIBM with more muscle function.http://www.ncbi.nlm.nih.gov/pubmed/21517694

Proof concept for clinical justification of network mapping for personalized cancer therapeutics. Cancer Gene Ther. 2007; 14:686-95.
To identify signature targets associated with patient-specific cancer lesions based on tumor versus normal tissue differential protein and mRNA coexpression patterns for the purpose of synthesizing cancer-specific customized RNA interference knockdown therapeutics. Analysis of biopsied tissue involved two-dimensional difference in-gel electrophoresis (2D-DIGE) analysis coupled with MALDI-TOF/TOF mass spectrometry for proteomic assessment. Standard microarray techniques were utilized for mRNA analysis. Priority was assigned to overexpressed protein targets with co-overexpressed genes with a high likelihood of functional nodal centrality in the cancer network as defined by the interactive databases BIND, HPRD and ResNet. HPLC-grade small interfering RNA (siRNA) duplexes were utilized to assess knockdown of target proteins in expressive cell lines as measured by western blot. Seven patients with metastatic cancer underwent biopsy. One patient (RW001) had biopsies from two disease sites 10 months apart. Seven priority proteins were identified, one for each patient (RACK 1, Ras related nuclear protein, heat-shock 27 kDa protein 1, superoxide dismutase, enolase1, stathmin1 and cofilin1). Prioritized proteins in RW001 from the two disease sites over time were the same. We demonstrated >80% siRNA inhibition of RACK 1 and stathmin1 of inexpressive malignant cell lines with correlated cell kill. Identification of functionally relevant target gene fingerprints, unique to an individual’s cancer, is feasible ‘at the bedside’ and can be utilized to synthesize siRNA knockdown therapeutics. Further animal safety testing followed by clinical study is recommended.
http://www.ncbi.nlm.nih.gov/pubmed/17541424

Cancer treatment involving the p53 gene. BUMC Proceedings 1999; 12:93-96.

Gene therapy for head and neck cancers. Oncology. 2001 Mar;15(3):303-8.
Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/11301829

Appendix

The role of computed tomography in the diagnosis of acute appendicitis. Am J of Surg 1999; 178:485-489.
Routine contrast-enhanced computed tomography (CECT) has been described as an accurate diagnostic imaging modality in patients with acute appendicitis. However, most patients with acute appendicitis can be diagnosed by clinical findings and physical exam alone. The role of CECT in patients suspected of having appendicitis but with equivocal clinical exams remains ill defined.
One hundred and seven consecutive patients who were thought to have appendicitis but with equivocal clinical findings and/or physical exams were imaged by CECT over a 12-month period. Oral and intravenous contrast-enhanced, spiral abdominal and pelvic images were obtained using 7-mm cuts. CECT images were interpreted by a board-certified radiologist. Main outcome measures included CECT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in the diagnosis of acute appendicitis, comparing CECT with ultrasound, and determining the impact of CECT on the clinical management of this patient population.
A group of 107 patients consisting of 44 males (41%) and 63 females (59%) with a median age of 33 years (range 13 to 89 years) were imaged with CECT to evaluate suspected appendicitis. Of the 107 CECTs performed, 11 false-positive and 3 false-negative readings were identified, resulting in a sensitivity of 92%, specificity of 85%, PPV of 75%, NPV of 95%, and an overall accuracy of 90%. Forty-three patients were imaged with ultrasound and CECT, and CECT had significantly better sensitivity and accuracy (30% versus 92% and 69% versus 88%, P<0.01). With regard to clinical management, 100% (36/36) of patients with appendicitis, and 4.2% (3/71) of patients without appendicitis underwent appendectomy. Therefore, the overall negative appendectomy rate was 7.6% (3/39).
CECT is a useful diagnostic imaging modality for patients suspected of having acute appendicitis but with equivocal clinical findings and/or physical exams. CECT is more sensitive and accurate than ultrasound and is particularly useful in excluding the diagnosis of appendicitis in those without disease.http://www.ncbi.nlm.nih.gov/pubmed/10670858

Gallbladder

Laparoscopic cholecystectomy for acalculus gallbladder disease. Presented at Southwestern Surgical Congress, April 1999.
Use of laparoscopic cholecystectomy (LC) to treat patients with symptoms due to gallstone disease is well established. However, use of LC for patients with acalculous gallbladder disease remains controversial. In this study, we examined the use of hepatobiliary iminodiacetic acid (HIDA) scans with cholecystokinin (CCK) infusion to identify patients with acalculous gallbladder disease who would benefit from LC. From December 1991 to February 1997, 4480 patients underwent cholecystectomy at Baylor University Medical Center, including 72 patients who underwent LC for acalculous disease following preoperative HIDA scan. We retrospectively analyzed their preoperative symptoms and workup. Follow-up was obtained by telephone questionnaire in 59 of 72 patients (82%). Overall, 48 of 59 patients (82%) reported an excellent outcome following LC. We found no significant difference in outcome in patients who underwent HIDA scan with CCK infusion, regardless of gallbladder ejection fraction or exacerbation of symptoms caused by the infusion. Preoperative symptom complex was also not predictive of postoperative outcome. LC is an effective treatment for patients with acalculous gallbladder disease. A preoperative HIDA scan with CCK infusion does not accurately predict treatment success or failure. Patients with a normal ejection fraction and absence of symptoms from a HIDA scan can still have excellent relief of symptoms after LC.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312225/?tool=pubmed

Usefulness of endoscopic ultrasound in patients at high risk of choledocholithiasis. BUMC Proceedings 2005; 18:211-13.
Endoscopic retrograde cholangiopancreatography (ERCP) has been considered the nonsurgical gold standard for the diagnosis and treatment of choledocholithiasis (CDL). Complications include a 0.1% to 1.3% mortality rate and a 5% to 19% morbidity rate, including a reported 1.8% to 6.7% incidence of postprocedure pancreatitis. Twenty-seven percent to 67% of ERCPs done for suspected choledocholithiasis ultimately have negative results. Endoscopic ultrasound (EUS) has been proposed as an alternate means of diagnosing choledocholithiasis that may eliminate the need for ERCP and its associated morbidities in certain patients.
Retrospective chart review identified 30 patients who underwent EUS with or without ERCP for suspected choledocholithiasis. Reports of all procedures performed were obtained and data were collected on all biliary abnormalities identified on both EUS and ERCP.
Pancreaticobiliary abnormalities were identified in 27 of 30 patients (90%) at EUS. Most common diagnoses included CDL (n = 9, 30%), biliary sludge (n = 11, 37%), pancreatitis (n = 8, 27%), and cholelithiasis (n = 7, 23%). Subsequent ERCP was performed in 14 patients (47%). Indications included a diagnosis of CDL by EUS (n = 9) and abnormal liver function tests (n = 5). CDL was identified in 5 of 14 patients (36%), and microlithiasis/biliary sludge was identified in an additional 5 patients (36%). In 4 patients, CDL was identified by EUS but not by ERCP. ERCP did not identify any new cases of CDL after EUS: of 21 patients without evidence of CDL on EUS, none were subsequently shown to have CDL or to develop any complications related to common duct stones.
EUS is an effective method of diagnosing CDL. It demonstrates both a high sensitivity and specificity for identifying common bile duct stones. Its use as a screening modality in patients suspected of having CDL may allow more selective use of ERCP. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200726/?tool=pubmed

Hernia

Routine Ilioinguinal nerve excision in inguinal hernia repairs. Oral presentation Feb 2004 North Texas Chapter ACS Meeting, Oral presentation April 2004 Southwestern Surgical Congress

Routine ilioinguinal nerve excision in inguinal hernia repairs. Am J Surg 2004; 188:736-40.
Chronic inguinal neuralgia is one of the most significant complications following inguinal hernia repair. Routine ilioinguinal nerve excision has been proposed as a means to avoid this complication. The purpose of this report is to evaluate the long-term outcomes of neuralgia and paresthesia following routine ilioinguinal nerve excision compared to nerve preservation.
Retrospective chart review identified 90 patients who underwent Lichtenstein inguinal hernia repairs with either routine nerve excision (n = 66) or nerve preservation (n = 24). All patients were contacted and data was collected on incidence and duration of postoperative neuralgia and paresthesia. Comparison was made by chi(2) analysis.
The patients with routine neurectomy were similar to the group without neurectomy based on gender (male/female 51/15 vs. 19/5) and mean age (68 +/- 14 vs. 58 +/- 18 years). In the early postoperative period (6 months), the incidence of neuralgia was significantly lower in the neurectomy group versus the nerve preservation group (3% vs. 26%, P <0.001). The incidence of paresthesia in the distribution of the ilioinguinal nerve was not significantly higher in the neurectomy group (18% vs. 4%, P = 0.10). At 1 year postoperatively, the neurectomy patients continued to have a significantly lower incidence of neuralgia (3% vs. 25%, P = 0.003). The incidence of paresthesia was again not significantly higher in the neurectomy group (13% vs. 5%, P = 0.32). In patients with postoperative neuralgia, mean severity scores on a visual analog scale (0-10) were similar in neurectomy and nerve preservation patients at all end points in time (2.0 +/- 0.0 to 2.5 +/- 0.7 vs. 1.0 +/- 0.0 to 2.2 +/- 1.5). In patients with postoperative paresthesia, mean severity scores on a visual analog scale (0-10) were similar in the neurectomy and nerve preservation patients at 1 year (2.5 +/- 2.2 vs. 4.0 +/- 0.0) and 3 years (3.5 +/- 2.9 vs. 4.0 +/- 0.0).
Routine ilioinguinal neurectomy is associated with a significantly lower incidence of postoperative neuralgia compared to routine nerve preservation with similar severity scores in each group. There is a trend towards increased incidence of subjective paresthesia in patients undergoing routine neurectomy at 1 month, but there is no significant increase at any other end point in time. When performing Lichtenstein inguinal hernia repair, routine ilioinguinal neurectomy is a reasonable option.http://www.ncbi.nlm.nih.gov/pubmed/15619492

Other

Kuhn JA, Fisher T, Livingston S. Innovations in surgical oncology at Baylor University Medical Center. BUMC Proceedings 2008;21:33-36. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190549/?tool=pubmed

Kuhn JA, Roberts WC. Joseph Allen Kuhn, MD: a conversation with the editor. Proc (Bayl Univ Med Cent). 2008 Jan;21(1):33-6. http://www.ncbi.nlm.nih.gov/pubmed/18209756

 

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