Melinda A. Maggard

Meta-analysis: surgical treatment of obesity.

Context The effectiveness of surgical therapy in the treatment of obesity is unclear. Contribution Many published studies of obesity surgery have significant limitations, and case series make up much of the evidence. Evidence is complicated by the heterogeneity of procedures studied. However, surgery can result in substantial amounts of weight loss (20 to 30 kg) for markedly obese individuals. One cohort study documented weight loss for 8 years with associated improvements in comorbid conditions, such as diabetes. Complications of surgery appear to occur in about 20% of patients. Implications Those considering surgical treatment for obesity should understand that, although patients who have surgery can lose substantial amounts of weight, the evidence base for these treatments is limited. The Editors The prevalence of obesity in the United States is reaching epidemic proportions. An estimated 30% of individuals met the criteria for obesity in 19992002 (1, 2), and many industrialized countries have seen similar increases. The health consequences of obesity include heart disease, diabetes, hypertension, hyperlipidemia, osteoarthritis, and sleep apnea (3-7). Weight loss of 5% to 10% has been associated with marked reductions in the risk for these chronic diseases and with reducing the incidence of diabetes (8-14). The increasing numbers of obese individuals have led to intensified interest in surgical treatments to achieve weight loss, and a variety of surgical procedures have been used (Figure 1). Bariatric surgery was first performed in 1954 with the introduction of the jejunoileal bypass, which bypasses a large segment of small intestine by connecting proximal small intestine to distal small intestine. With this procedure, weight loss occurs secondary to malabsorption from reduction of upstream pancreatic and biliary contents. However, diarrhea and nutritional deficiencies were common, and this procedure was discontinued because of the complication of irreversible hepatic cirrhosis. With the development of surgical staplers came the introduction of gastroplasty procedures by Gomez in 1981 (15) and Mason in 1982 (16). In these early procedures, the upper portion of the stomach was stapled into a small gastric pouch with an outlet (that is, a stoma) to the remaining distal stomach, which limited the size of the meal and induced early satiety. These procedures were prone to staple-line breakdown or stoma enlargement and were modified in turn by the placement of a band around the stoma (vertical banded gastroplasty). Figure 1. Surgical procedures. The first gastric bypass was reported in 1967 by Mason and Ito (17). It combined the creation of a small gastric pouch with bypassing a portion of the upper small intestine. Additional modifications resulted in the Roux-en-Y gastric bypass (RYGB), a now common operation that involves stapling the upper stomach into a 30-mL pouch and creating an outlet to the downstream small intestine. The new food limb joins with the biliopancreatic intestine after a short distance. This procedure, performed laparoscopically or by using an open approach, generates weight loss by limiting gastric capacity, causing mild malabsorption, and inducing hormonal changes. A second common technique, particularly outside of the United States, is the laparoscopic adjustable gastric band. This device is positioned around the uppermost portion of the stomach and can be adjusted to allow tailoring of the stoma outlet, which controls the rate of emptying of the pouch and meal capacity. Another procedure, preferred by a number of surgeons, is the biliopancreatic bypass, which combines a limited gastrectomy with a long Roux limb intestinal bypass that creates a small common channel (that is, an intestine where food and biliopancreatic contents mix). This procedure can be combined with a duodenal switch, which maintains continuity of the proximal duodenum with the stomach and uses a long limb Roux-en-Y bypass to create a short common distal channel. These latter 2 procedures generate weight loss primarily through malabsorption. Recent worldwide survey data from 2002 and 2003 show that gastric bypass is the most commonly performed weight loss procedure (65.1%) (18). Slightly more than half of gastric bypasses are done laparoscopically. Overall, 24% of cases are laparoscopic adjustable band procedures; 5.4% are vertical banded gastroplasties; and 4.9% are biliopancreatic diversion, with or without the duodenal switch. In California, the number of bariatric cases increased 6-fold between 1996 and 2000 (19), from 1131 cases to 6304; an estimated 140000 procedures were performed in the United States in 2004. With this escalation in the number of procedures, there have been reports of high postoperative complication rates (20-24). Because of these reports and the increasing use of obesity surgery, we were asked to review the literature to estimate the effectiveness of bariatric surgery relative to nonsurgical therapy for weight loss and reduction in preoperative obesity-related comorbid conditions. We were also asked to compare outcomes of surgical techniques. This paper is part of a larger evidence report titled Pharmacological and Surgical Treatment of Obesity, which was prepared for the Agency for Healthcare Research and Quality and is available at www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.19289. Methods Literature Search and Selection We began with an electronic search of MEDLINE on 16 October 2002, followed by a search of EMBASE and subsequent periodic search updates (on 22 May, 2 June, 12 June, and 3 July 2003). We also assessed existing reviews of surgical therapy for obesity (10, 25, 26). Three reviewers independently reviewed the studies, abstracted data, and resolved disagreements by consensus (2 reviewers per study). The principal investigator settled any unresolved disagreements. We focused on studies that assessed surgery and used a concurrent comparison group. This category includes randomized, controlled trials (RCTs); controlled clinical trials; and cohort studies. A brief scan of the literature showed that these types of studies were rare. Therefore, we also elected to include case series with 10 or more patients, since these studies can be used to assess adverse events and could potentially augment the efficacy data from comparative studies. Publication bias is one potential limitation of analyzing the available literature because poor or negative results are not as likely to be reported as are successes or positive results. Extraction of Study-Level Variables We abstracted data from the articles, including number of patients and comorbid conditions, adverse events, types of outcome measures, and time from intervention until outcome. Detailed data were also collected on characteristics of the study samples, including median age, percentage of women, median baseline weight (in kilograms or body mass index [BMI]), percentage of patients with comorbid conditions at baseline (diabetes, hypertension, dyslipidemia, and sleep apnea), percentage of improvement or resolution of preexisting comorbid conditions, and median follow-up time. We also recorded whether the case series studies reported on consecutive patients. Choice of Outcomes The main outcomes of interest were weight loss, mortality, complication rates, and control of obesity-related comorbid conditions. We used the most commonly reported measurement of weight loss, that is, kilograms, which allowed us to include the greatest number of studies. Among 111 surgical studies reporting weight loss, 43 reported weight loss in kilograms or pounds, 17 reported excess weight loss or some variant, 46 reported both of these outcomes, and 5 reported neither. A total of 89 studies had sufficient data to be included in the weight loss analysis. Because weight loss achieves health benefits primarily by reducing the incidence or severity of weight-related comorbid conditions, we also compared the effects on these outcomes. Quality of life, an important outcome in assessing tradeoffs between benefits and risks, was reported infrequently. Statistical Analyses Because we included both comparative studies and case series, we conducted several types of analyses. The vast number of types of surgical procedures and technical variations required that we aggregate those that were clinically similar and identify the comparisons that were of most interest to the clinical audience. On the basis of discussions with bariatric surgeons, we categorized obesity surgery procedures by procedure type (for example, gastric bypass, vertical banded gastroplasty), laparoscopic or open approach, and specific surgical details such as length of Roux limb (see the larger evidence report for details). Analysis of the Efficacy of Surgical Weight Loss We extracted the mean weight loss and standard deviation at 12 postoperative months and at the maximum follow-up time (36 months). These times were chosen because they are clinically relevant and are most commonly reported. Of the 89 weight loss studies, 71 reported baseline BMI (average, 47.1 kg/m2), 16 reported baseline weight in kilograms or pounds (average, 123.3 kg), and 2 did not report either. The average age of patients was 38 years, and more than three quarters were women. For comparative studies that reported a within-study comparison of 2 procedures, a mean difference was calculated. Mean differences were pooled by using a random-effects model, and 95% CIs were estimated; the same method was used to determine a pooled mean weight loss for each group considering all studies combined. However, mean difference in weight loss was not calculated. Analysis of Surgery Mortality We recorded the number of deaths observed and the total number of patients in each procedure group. If the study self-identified the deaths as early or postoperative or as occurring within 30 days of the surgery, we termed these early deaths. If the

The aging population and its impact on the surgery workforce.

Objective To predict the impact of the aging population on the demand for surgical procedures. Summary Background Data The population is expanding and aging. According to the US Census Bureau, the domestic population will increase 7.9% by 2010, and 17.0% by 2020. The fastest growing segment of this population consists of individuals over the age of 65; their numbers are expected to increase 13.3% by 2010 and 53.2% by 2020. Methods Data on the age-specific rates of surgical procedures were obtained from the 1996 National Hospital Discharge Survey and the National Survey of Ambulatory Surgery. These procedure rates were combined with corresponding relative value units from the Centers for Medicare and Medicaid Services. The result quantifies the amount of surgical work used by an average individual within specific age groups (<15 years old, 15–44 years old, 45–64 years old, 65+ years old). This estimate of work per capita was combined with population forecasts to predict future use of surgical services. Results Based on the assumption that age-specific per capita use of surgical services will remain constant, we predict significant increases (14–47%) in the amount of work in all surgical fields. These increases vary widely by specialty. Conclusions The aging of the US population will result in significant growth in the demand for surgical services. Surgeons need to develop strategies to manage an increased workload without sacrificing quality of care.

Updated population-based review of carcinoid tumors.

Objective:To determine the population-based incidence, anatomic distribution, and survival rates of gastrointestinal carcinoid tumors. Background:Carcinoid tumors arise from neuroendocrine cells and may develop in almost any organ. Many textbooks and articles represent single institution studies and report varying incidence rates, anatomic distribution of tumors, and patient survival rates. Population-based statistics remain largely unknown. Methods:Data was obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results program (1973 to 1997). Incidence rates, distribution, and 5-year survival rates were analyzed. Multivariate Cox regression was used to identify predictors of survival using age, race/ethnicity, gender, and tumor characteristics (size, lymph node status, and stage). Results:Of the 11,427 cases analyzed, the average age was 60.9 years, and 54.2% were female. The overall incidence rates for carcinoid tumors have increased significantly over the past 25 years, although rates for some sites have decreased (eg, appendix). The gastrointestinal tract accounted for 54.5% of the tumors. Within the gastrointestinal tract, the small intestine was the most common site (44.7%), followed by the rectum (19.6%), appendix (16.7%), colon (10.6%), and stomach (7.2%). The 5-year survival rates for the most common gastrointestinal sites were stomach (75.1%), small intestine (76.1%), appendix (76.3%), and rectum (87.5%). Conclusions:Using national, population-based cancer registry data, this study demonstrates that (1) incidence rates for carcinoid tumors have changed, (2) the most common gastrointestinal site is not the appendix (as is often quoted), but the small intestine, followed in frequency by the rectum, and (3) survival rates differ between individual anatomic sites.

Long-term results of pediatric liver transplantation: an analysis of 569 transplants.

OBJECTIVE To analyze a single centers 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

A 10-Year Outcomes Evaluation of Mucinous and Signet-Ring Cell Carcinoma of the Colon and Rectum

PURPOSEMost studies examining mucinous or signet-ring cell colorectal cancers are single institution reports. This study used a national cancer registry to analyze the epidemiology and survival outcomes of these two subtypes of colorectal cancer compared with adenocarcinoma tumors.METHODSAll patients diagnosed with mucinous (n = 16,991), signet-ring cell (n = 1,522), or adenocarcinoma (n = 146,115) colorectal cancer in the Surveillance, Epidemiology, and End Results database (1991–2000) were evaluated. Analyses were performed to obtain age-adjusted incidence rates, stage at presentation, tumor grade, and five-year relative survival for each subtype.RESULTSMucinous were slightly more common in females (53.4 percent). Incidence rates per 100,000 persons were: mucinous, 5.5; signet-ring cell, 0.6; and adenocarcinoma 46.6. The annual percent change during ten years was stable for mucinous, increased for signet-ring cell (4.8 percent; P < 0.05), and decreased for adenocarcinoma (−1.1 percent; P < 0.05). Fewer mucinous (18 percent) and signet-ring cell (21 percent) tumors were located in the rectum compared with adenocarcinoma (29 percent). Signet-ring cell presented at later stage (III/IV, 80.9 percent) more often than mucinous (52.8 percent) and adenocarcinoma (49.5 percent), and also had worse tumor grade (high grade: signet-ring cell, 73.5 percent; mucinous, 20.9 percent; adenocarcinoma, 17.5 percent). Relative five-year survival was worse for signet-ring cell than mucinous or adenocarcinoma.CONCLUSIONSWe present a large population-based review of colorectal cancer subtypes by analyzing national data from the past decade. Although the incidence of colorectal adenocarcinoma is decreasing in the United States, mucinous and signet-ring cell subtypes are stable and increasing, respectively. Importantly, it seems that the signet-ring cell subtype has worse outcomes, whereas survival rates for mucinous tumors are similar to adenocarcinomas.

Malignancies of the Appendix: Beyond Case Series Reports

PURPOSEA comprehensive analysis was performed for five histologic types of appendiceal tumors to compare incidence, clinicopathologic features, survival, and appropriateness of surgery.METHODSAll patients diagnosed with mucinous adenocarcinoma (n = 951), adenocarcinoma (n = 646), carcinoid (n = 435), goblet (n = 369), and signet-ring cell (n = 113) in the Surveillance, Epidemiology, and End Results database (1973–2001) were analyzed. Evaluation of incidence, stage, and five-year relative survival were determined for each histology. The appropriateness of the operative procedure (i.e. , appendectomy vs. colectomy) was examined by tumor type and size.RESULTSTumor incidence, patient demographics, survival outcomes, and appropriateness of surgery varied significantly among the different appendiceal tumor histologies. The most common appendiceal tumors were mucinous. With regard to patient demographics, carcinoids presented at an earlier mean age of 41 years and 71 percent were female (P < 0.001 for both). Overall five-year survival was highest for carcinoid (83 percent) and lowest for signet ring (18 percent). Although current guidelines specify that a right hemicolectomy (rather than an appendectomy) be performed for all noncarcinoid tumors and carcinoid tumors >2 cm, we found that 30 percent of noncarcinoids underwent appendectomy. Similarly, 28 percent of carcinoids >2 cm under-went appendectomy, which is a lesser resection than is indicated.CONCLUSIONSThis study provides a population-based analysis of epidemiology, tumor characteristics, survival, and quality of care for appendiceal carcinomas. This characterization provides a novel description of the presentation and outcomes for malignancies of the appendix and highlights that a substantial number of patients with appendiceal tumors may not be receiving appropriate surgical resection.

Do young colon cancer patients have worse outcomes

Previous studies on colon cancer have noted rising incidence rates among young individuals and suggest that they may have more aggressive disease and worse 5-year survivals than their older counterparts. Our study uses a nationwide population-based cancer registry to analyze colon cancer presentations and outcomes in a young versus an older population. The records of patients with colon carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) national cancer database (1991–1999). Two cohorts based on age at diagnosis (20–40 years, n = 1334 vs. 60–80 years, n = 46,457) were compared for patient and tumor characteristics, treatment, and 5-year cancer-specific survival. A multivariate Cox regression was performed to identify predictors of survival. The young group had a higher proportion of black and Hispanic patients than did the older group (p < 0.001). Young patients had less stage I or II disease, more stage III or IV disease (p < 0.001), and worse-grade (poorly differentiated or anaplastic) tumors (p < 0.001). The 5-year stage-specific survival was similar for stage I and III disease (p = NS) but was significantly better for young patients with stage II and IV disease (p < 0.01). Using a nationally representative cancer registry, we found that young colon cancer patients tend to have later-stage and higher-grade tumors. However, they have equivalent or better 5-year cancer-specific survival compared to older patients. This population-based finding contradicts prior single-institution reports.

Fas ligand gene transfer to renal allografts in rats : Effects on allograft survival

BACKGROUND Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection. METHODS The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis (RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9 x 10(9) plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting. RESULTS Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P < 0.05). CONCLUSIONS (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.

Are Survival Rates Different for Young and Older Patients With Rectal Cancer

PURPOSEAlthough it is generally believed that young patients with rectal cancer have worse survival rates, no comprehensive analysis has been reported. This study uses a national-level, population-based cancer registry to compare rectal cancer outcomes between young vs. older populations.METHODSAll patients with rectal carcinoma in the Surveillance, Epidemiology, and End Results cancer database from 1991 to 1999 were evaluated. Young (range, 20–40 years; n = 466) and older groups (range, 60–80 years; n = 11,312) were compared for patient and tumor characteristics, treatment patterns, and five-year overall and stage-specific survival. Cox multivariate regression analysis was performed to identify predictors of survival.RESULTSMean ages for the groups were 34.1 and 70 years. The young group was comprised of more black and Hispanic patients compared with the older group (P < 0.001). Young patients were more likely to present with late-stage disease (young vs. older: Stage III, 27 vs. 20 percent respectively, P < 0.001; Stage IV, 17.4 vs. 13.6 percent respectively, P < 0.02). The younger group also had worse grade tumors (poorly differentiated 24.3 vs. 14 percent respectively, P < 0.001). Although the majority of both groups received surgery (85 percent for each), significantly more young patients received radiation (P < 0.001). Importantly, overall and stage-specific, five-year survival rates were similar for both groups (P = not significant).CONCLUSIONSAlthough previous studies have found young rectal cancer patients to have poorer survival compared with older patients, this population-based study shows that young rectal cancer patients seem to have equivalent overall and stage-specific survival.

Cancer-directed surgery for localized disease: decreased use in the elderly.

Background: Previous studies report underuse of radiation and chemotherapy in the elderly, yet few have examined the rates of use (or underuse) of surgery. Using national data, we examined rates of surgical resection for patients with local-stage cancers.Methods: By using the Surveillance, Epidemiology, and End Results database (1988–1997), patients (≧40 years) were identified with localized adenocarcinoma of the breast, esophagus, stomach, pancreas, colon, or rectum; non–small-cell lung carcinoma; and sarcoma (n = 200,360). Rates of cancer-directed surgery (CDS) were compared across age groups (at 5-year intervals). Multivariate regression was used to identify predictors of receipt of CDS in each tumor group.Results: Rates of CDS declined steadily with increasing age for all nine localized tumors. Most striking were the low rates of CDS for patients >70 years with esophagus, stomach, pancreas, and lung cancers (range, 0%–83%). However, CDS rates were >90% for breast and colon and >84% for rectal cancer in all age groups. Multivariate regression found lower odds of CDS for elderly patients for all cancers except colon. For example, age significantly decreased the odds of receiving CDS beginning at 60 years for lung cancer (odds ratio [OR], .550; P = .03), at 70 years for liver cancer (OR, .109; P = .003), and at 80 years for pancreatic cancer (OR, .120; P < .05).Conclusions: Although CDS for localized disease is being performed regularly in the elderly for some cancers (e.g. breast, colon, and rectum), this analysis shows that elderly patients are not receiving surgery for many potentially curable cancers. Whether these rates are appropriate or too low requires further evaluation. This is particularly essential because our population is aging.