Lawrence T. Kim

Factors Affecting Recurrence following Incisional Herniorrhaphy

The purpose of this study was to determine the influence of chronic illness, obesity, and type of repair on the likelihood of recurrence following incisional herniorrhaphy. The medical records of 77 patients who underwent elective repair of a midline incisional hernia at the Dallas Veterans Affairs Medical Center between 1991 and 1995 were reviewed. Demographic data, presence of chronic illnesses, type of repair, and presence of recurrence were noted. Ninety-six percent of the patients were men, with an average age of 59 years. More than 50% of the patients had chronic lung or cardiac diseases and more than 40% weighed ≥120% of their ideal body weight and had a body mass index (BMI) ≥30. Sixty-two percent of the patients underwent primary reapproximation of the fascia (tissue repair), whereas 38% underwent repair with prosthetic material (prosthetic repair). The overall recurrence rate was 45%, with a median follow-up of 45 months (range 6–73). Seventy-four percent of the recurrences presented within 3 years of repair. The recurrence rate for those patients undergoing a tissue repair was 54%, whereas the recurrence rate following prosthetic repair was 29%. The incidence of recurrence for patients with pulmonary or cardiac disease or diabetes mellitus was similar to that of patients without these illnesses. The percent ideal body weight and BMI of patients who developed a recurrent hernia, particularly following a prosthetic repair, were significantly greater than those of patients whose repairs remained intact. These data strongly support the use of prosthetic repairs for incisional hernias, particularly in patients who are overweight.

Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes

PURPOSE Peroxisome proliferator-activated receptor gamma (PPARgamma) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted. PATIENTS AND METHODS Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents). RESULTS Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance. CONCLUSION TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.

Comparison of Laparoscopic and Open Repair With Mesh for the Treatment of Ventral Incisional Hernia A Randomized Trial

BACKGROUND Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair. DESIGN Prospective randomized trial conducted between February 1, 2004, to January 31, 2007. SETTING Four Veterans Affairs medical centers. PARTICIPANTS One hundred sixty-two patients with ventral incisional hernias. INTERVENTIONS Standardized laparoscopic or open repair. MAIN OUTCOME MEASURES Overall complication rates at 8 weeks and the odds of complications, adjusted for study site, body mass index, and hernia type. RESULTS Of the 162 randomized patients, 146 underwent surgery (73 open and 73 laparoscopic repairs). Complications were less common in the laparoscopic group (23 patients [31.5%]) compared with the open repair group (35 patients [47.9%]; adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.22-0.91; P = .03). Surgical site infection through 8 weeks was less common in the laparoscopic group (5.6% vs 23.3%; AOR, 0.2; 95% CI, 0.1-0.6). The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks (95% CI, 1.0-29.3; P = .04). Time to resume work activities was shorter for the laparoscopic group than for the open repair group (median, 23.0 days vs 28.5 days), with an adjusted hazard ratio of 0.54 (95% CI, 0.28-1.04; P = .06). Overall recurrence at 2 years was 12.5% in the laparoscopic group and 8.2% in the open repair group (AOR, 1.6; 95% CI, 0.5-4.7; adjusted P = .44). CONCLUSIONS Laparoscopic repair was associated with fewer, albeit more severe, complications and improved some patient-centered outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00240188.

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

BACKGROUND The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). METHODS AND RESULTS We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. CONCLUSION Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.

Accuracy of Surgeon-performed Ultrasound in Parathyroid Localization

Ultrasound is one of the preferred modalities for localization of abnormal parathyroids. Accuracy of ultrasound is technician-dependent. This study was undertaken to determine the accuracy of surgeon-performed ultrasound (SPU) for the localization of parathyroid tumors in comparison to radiology-performed ultrasound (RPU) and nuclear scintigraphy (NS). In this series 74 consecutive patients with untreated primary hyperparathyroidism underwent SPU at the initial clinic visit; 21 of these patients did not undergo surgery and are excluded from the analysis. Of the 53 patients remaining, RPU was obtained in 26, and 52 patients underwent NS. Directed parathyroidectomy was performed with use of the intraoperative parathyroid hormone assay (IOPTH). In all, 46 patients had a single adenoma as indicated by IOPTH and final pathology. Two patients had double gland disease, and 5 patients had multi-gland hyperplasia. The sensitivity of SPU was 82% and the specificity was 90% in detecting the diseased glands on the correct side (right versus left). The sensitivity for RPU was 42% and the specificity was 92% (n = 26). The sensitivity of NS was 44% and the specificity was 98% (n = 52). In only one case did RPU or NS detect a gland not found by SPU. SPU can be done with accuracy comparable to other ultrasound series in the literature, and it may be superior to RPU or NS in some institutions. It is important for surgeons to be aware of local institutional expertise when relying on RPU and NS during preoperative evaluation prior to directed parathyroidectomy.

Tension-free inguinal hernia repair: the design of a trial to compare open and laparoscopic surgical techniques

BACKGROUND Inguinal hernia is a common condition in men and represents a large component of health-care expenditures. Approximately 700,000 herniorrhaphies are performed each year in the United States. The most effective method of repair of an inguinal hernia is not known. STUDY DESIGN A multicenter, randomized, clinical trial was designed to compare open tension-free inguinal hernia repair with laparoscopic tension-free repair on recurrence rates, complications, patient-centered outcomes, and cost. The study design called for randomization of 2,200 men over a period of 3 years. These men will be followed for a minimum of 2 years. This will allow determination of as little as a 3% absolute difference in recurrence rates with 80% power. Randomization is stratified by hospital, whether the hernia is unilateral or bilateral and whether the hernia is primary or recurrent. RESULTS This is a report of the study design and current status. The study involves 14 Veterans Affairs medical centers with previous experience in laparoscopic hernia repair. After 35 months of enrollment, 2,165 men were randomized and recruitment was then closed. The majority of the patients (82.3%) had unilateral hernias and 90.6% of the hernias were primary. Sixty-seven percent of the patients had an outpatient operation. CONCLUSIONS We report successful recruitment into a large multicenter trial comparing open and laparoscopic hernia repair. When followup is complete, this study will provide data regarding both clinical (recurrence rates) and patient-centered outcomes.

Seroma in ventral incisional herniorrhaphy: incidence, predictors and outcome

BACKGROUND Factors leading to seroma following ventral incisional herniorrhaphy (VIH) are poorly understood. METHODS Between 2004 and 2006, patients were prospectively randomized at 4 Veterans Affairs hospitals to undergo laparoscopic or open VIH. Patients who developed seromas within 8 weeks postoperatively were compared with those who did not. Multivariate analyses were performed to identify predictors of seroma. RESULTS Of 145 patients who underwent VIH, 24 (16.6%) developed seromas. Patients who underwent open VIH had more seromas than those who underwent laparoscopic VIH (23.3% vs 6.8%, P = .011). Seroma patients had hernias that were never spontaneously reducible (0% vs 21%, P = .015), had more abdominal incisions preoperatively (mean, 2.4 vs 1.8; P = .037), and were less likely to have drain catheters placed than those without seromas (30.0% vs 63.1%, P = .011). In multivariate analyses, open VIH predicted seroma (odds ratio, 5.5; 95% confidence interval, 1.6-18.8), as well as the specific hospital at which the procedure was performed. Spontaneous resolution occurred in 71% of seromas; 29% required aspiration. CONCLUSIONS Procedural characteristics and hernia characteristics rather than patient comorbidities predicted seroma in VIH.

Long-term glucose control and risk of perioperative complications

BACKGROUND The impact of long-term preoperative glucose control on short-term surgical complications is unclear. We investigated whether preoperative hemoglobin A1c (HA(1c)) levels correlated with the risk of postoperative complications. METHODS A database of 38,989 patients undergoing major surgical procedures from October 1996 to May 2007 was reviewed. Of these patients, 2,960 were diagnosed diabetic with a HA(1c) level within 30 days before their operation. National Surgical Quality Improvement Program (NSQIP) definitions were used in determining postoperative complications. RESULTS Of 36,039 nondiabetic patients, 5,095 experienced 1 or more complications (14.1%). In 2,960 diabetic patients, 780 diabetic patients had 1 or more complications (26.4%) (P <or=.001). Mortality was higher in diabetics than nondiabetics (4.2% vs 1%, respectively; P <.0001). There was no correlation between HA(1c) levels and risk of complication, type of complication, or death. CONCLUSIONS Although our data show an increased risk of surgical complications in diabetics, there was no detectable correlation between risk of complication and HA(1c) level. This suggests that poor long-term glucose control may not play a major role in determining short-term surgical morbidity.

Postoperative colorectal cancer surveillance.

The postoperative surveillance of patients who have undergone definitive initial therapy for colorectal cancer (CRC) is a topic of considerable controversy. The controversy exists largely because it has been difficult to prove a survival advantage for asymptomatic patients participating in posttreatment surveillance, compared with symptom-directed surveillance. For a benefit in survival to be realized for a surveillance program, it is essential not only that recurrent disease be identified, but also that potentially curative treatment options be available. Given this linkage, a surveillance program must be judged not only by its ability to identify disease recurrence, but also by the merits of available therapy for recurrent disease. The purpose of this article is to review the literature to familiarize the physician with the available data related to the possible benefits of surveillance both in terms of identification of disease and the curative treatment options for recurrent CRC.

Focal adhesions and associated proteins in medullary thyroid carcinoma cells

BACKGROUND In medullary thyroid carcinoma (MTC), mutations in the RET protooncogene lead to oncogenic transformation. RET activation in other cell types has been shown to cause phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK), paxillin, and p130(CAS). We hypothesized that adhesion-dependent signaling might be deranged in MTC cells. METHODS Indirect immunofluorescence was used to label beta(1) integrin, FAK, paxillin, and p130CAS. Rhodamine-labeled phalloidin was used to visualize actin microfilaments. Phosphorylated protein was detected by immunoprecipitation followed by Western blotting for phosphotyrosine. MTC cell invasiveness was quantified using a modified Boyden chamber assay. RESULTS Clustering of beta(1) integrin, FAK, paxillin, and p130(CAS) into focal adhesions were not detected in MTC cells under any conditions, although clustering was seen as expected in control HeLa cells. Despite this failure, FAK, paxillin and p130(CAS) were all found to be phosphorylated. Actin microfilaments were generally not seen although in a few cells, small, poorly formed microfilaments could be detected. MTC cells invaded poorly as compared with highly invasive cell lines. However a clear difference was noted between invasiveness on growth factor depleted Matrigel and regular Matrigel. CONCLUSIONS In MTC cells, focal adhesions are not seen in response to interaction with extracellular matrix. Consistent with this failure, actin microfilaments are absent or poorly formed and invasion is weak. Despite the absence of focal adhesions, focal adhesion proteins remain phosphorylated, even though in normal cells their signaling activity is dependent on focal adhesion formation. Deranged adhesion-dependent signaling may contribute to MTC pathogenesis.