Surgery

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2012-02-01

Error training: Missing link in surgical education

Debra A. DaRosa, Carla M. Pugh — 2011-11-17

People make mistakes. Human error is inevitable and must be anticipated, especially in environments where novices are developing new knowledge and skills. In medical education, faculty members are charged with supervising their residents to minimize chances of patient care errors. This is no small challenge for faculty given the consequences of errors to patients, the psychological cost to learners, and the ramifications for the faculty member and hospital from the fiscal, resource, and medicolegal perspectives. Yet, if decision-making and technical errors are bound to occur during a physician’s career because of human infallibility, and residents have uneven and limited exposure to errors because of responsible faculty oversight, how will they graduate fully prepared to recognize and manage an error when one does occur? Satava explained that faculty members spend so much time teaching residents how to do the correct thing that they forget to explicitly teach how to avoid errors or fix it when one has occurred. Residents encounter errors during their residency but this “catch as catch can” strategy cannot provide a sufficient and balanced array of opportunities to hone the perceptual, cognitive, and technical skills needed to prevent, recognize, or manage the range of potential errors.

Creating a learning healthcare system in surgery: Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP) at 5 years

2011-12-01

There are increasing efforts towards improving the quality and safety of surgical care while decreasing the costs. In Washington state, there has been a regional and unique approach to surgical quality improvement. The development of the Surgical Care and Outcomes Assessment Program (SCOAP) was first described 5 years ago. SCOAP is a peer-to-peer collaborative that engages surgeons to determine the many process of care metrics that go into a “perfect” operation, track on risk adjusted outcomes that are specific to a given operation, and create interventions to correct under performance in both the use of these process measures and outcomes. SCOAP is a thematic departure from report card oriented QI. SCOAP builds off the collaboration and trust of the surgical community and strives for quality improvement by having peers change behaviors of one another. We provide, here, the progress of the SCOAP initiative and highlight its achievements and challenges.

Prevention of medical accidents caused by defective surgical instruments

2011-09-26

Background: The malfunctioning of surgical instruments may lead to serious medical accidents. Limited information is available on the risk of defective instruments. The purpose of these study is to demonstrate the features of defective surgical instruments, to establish a strategy to reduce the risk of medical accidents.Methods: We studied 19,474 consecutive operations during 2007 to 2009 at our hospital. The data on defective instruments were collected based on the orders for repair of broken instruments and reports of near-miss incidents. Adverse events caused by defective instruments were also identified from reports of near-miss incidents.Results: A total of 1,775 nonfunctioning instruments were identified during the study period. Of these, 112 were found during operation. More than half of the defective instruments were tissue-grasping instruments, bone-boring/gnawing instruments, and instruments for endoscopic surgery. Wearing out and inappropriate use of instruments were 2 major causes of defects. The rest of the causes consisted of inadequate inspection and factory defects. Two near-miss incidents (incidence 10 per 100,000 operations) in endoscopic surgery were potentially critical, but the postoperative course was uneventful in each patient. The incidence of defects adjusted by the number of operations demonstrated that bone-boring/gnawing instruments and instruments for endoscopic surgery tend to be broken during surgery. Without inspection by the manufacturer, the incidence would be much higher for endoscopic instruments.Conclusion: Our data suggest that the appropriate use and adequate inspection of particular types of instruments are key for reducing the risk of medical accidents caused by defective surgical instruments.

Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases

2011-10-10

Background: The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known.Methods: Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0–5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection.Results: One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3–5) was lower (7 vs 18 months [P < .0001] and 50% vs 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0–1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0–1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs15 months [P = .03] and 48% vs 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis.Conclusion: In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.

Rates and patterns of death after surgery in the United States, 1996 and 2006

2011-10-05

Background: Nationwide rates and patterns of death after surgery are unknown.Methods: Using the Nationwide Inpatient Sample, we compared deaths within 30 days of admission for patients undergoing surgery in 1996 and 2006. International Classification of Diseases codes were used to identify 2,520 procedures for analysis. We examined the inpatient 30-day death rate for all procedures, procedures with the most deaths, high-risk cardiovascular and cancer procedures, and patients who suffered a recorded complication. We used logistic regression modeling to adjust 1996 mortality rates to the age and gender distributions for patients undergoing surgery in 2006.Results: In 1996, there were 12,573,331 admissions with a surgical procedure (95% confidence interval [CI], 12,560,171–12,586,491) and 224,111 inpatient deaths within 30 days of admission (95% CI, 221,912–226,310). In 2006, there were 14,333,993 admissions with a surgical procedure (95% CI, 14,320,983–14,347,002) and 189,690 deaths (95% CI, 187,802–191,578). Inpatient 30-day mortality declined from 1.68% in 1996 to 1.32% in 2006 (P < .001). Of the 21 procedures with the most deaths in 1996, 15 had significant declines in adjusted mortality in 2006. Among these 15 procedures, 8 had significant declines in operative volume. The inpatient 30-day mortality rate for patients who suffered a complication decreased from 12.10% to 9.84% (P < .001).Conclusion: Nationwide reporting on surgical mortality suggests that the number of inpatient deaths within 30 days of surgery has declined. Additional research to determine the underlying causes for decreased mortality is warranted.

Use of omentum or falciform ligament does not decrease complications after pancreaticoduodenectomy: Nationwide survey of the Japanese Society of Pancreatic Surgery

2011-10-10

Background: Wrapping is thought to prevent pancreatic fistula and postoperative hemorrhage for pancreaticoduodenectomy (PD), and we analyzed whether omentum/falciform ligament wrapping decreases postoperative complications after PD.Methods: This is a retrospective study of wrapping using the omentum/falciform ligament in patients that underwent PD between January 2006 and June 2008 in 139 institutions that were members of the Japanese Society of Pancreatic Surgery.Results: Ninety-one institutions responded to the questionnaires, and data were accumulated from 3,288 patients. The data from 2,597 patients were acceptable for analysis; 918 (35.3%) patients underwent wrapping and 1,679 patients did not. A pancreatic fistula occurred in 623 patients (37.3%) in the nonwrapping group, in comparison to 393 patients (42.8%) in the wrapping group (P = .006). The incidence of a grade B/C pancreatic fistula was lower in the nonwrapping group than the wrapping group (16.7% vs 21.5%; P = .002). An intra-abdominal hemorrhage occurred in 54 patients (3.2%) in the nonwrapping group, which was similar to the incidence in the wrapping group (32 patients; 3.5%). The mortality was 1.3% and 1.0% in nonwrapping and wrapping groups, respectively. A multivariate analysis revealed 7 independent risk factors for pancreatic fistula; male, hypoalbuminemia, soft pancreas, long operation time, extended resection, pylorus preservation, and omentum wrapping. There were 4 independent risk factors for early intra-abdominal hemorrhage and 2 independent risk factors for late intra-abdominal hemorrhage.Conclusion: This retrospective study revealed that omentum wrapping did not decrease the incidence of pancreatic fistula. An additional validation study is necessary to evaluate the efficacy of wrapping for PD.

Prophylactic central lymph node dissection for clinically node-negative papillary thyroid microcarcinoma: Influence on serum thyroglobulin level, recurrence rate, and postoperative complications

Yoon Kyoung So, Min Young Seo, Young-Ik Son — 2011-04-19

Background: In papillary thyroid microcarcinoma (PTMC), regional lymph node metastasis (LNM) is associated with a increased locoregional recurrence rate. Yet, prophylactic central lymph node dissection (CLND) targeting subclinical central LNM continues to be a matter of debate in the treatment of PTMC, which generally carries an excellent prognosis. The aim of our study was to investigate the benefits and risks of prophylactic CLND in patients with clinically node-negative PTMC.Methods: This study included 232 patients who underwent surgery for clinically node-negative PTMC from 1999 to 2006. Of these 232 patients, 113 underwent only total thyroidectomy (TT) and 119 underwent TT in conjunction with prophylactic bilateral CLND (TT with CLND). We then compared serum thyroglobulin (Tg) levels, recurrence rates, and postoperative complications between the 2 groups (TT only and TT with CLND).Results: The postoperative stimulated serum Tg level was significantly less in the TT with CLND group than in the TT only group (1.07 vs 2.24 ng/mL, respectively; P = .022). The stimulated Tg levels in the 2 groups became similar, however, after low-dose radioactive iodine treatment (0.44 ng/mL vs 0.69 ng/mL, respectively; P = 0.341). There was no significant difference in 3-year locoregional control rates after TT with CLND and TT only (98.3% vs 96.5%, respectively; P = .368). Although the frequency of permanent hypocalcemia was approximately 3 times greater in the TT with CLND group (5.6%) than in the TT only group (1.8%), this finding did not reach statistical significance.Conclusion: With prophylactic CLND, the postoperative Tg level can significantly decrease. However, prophylactic CLND is not helpful in decreasing short-term locoregional recurrence in patients with clinically node-negative PTMC. Finally, the risk of permanent hypocalcemia may increase after CLND.

Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: A population-based study

2011-10-05

Background: In a population-based study, we examined recurrence rates of acute pancreatitis (AP) after cholecystectomy performed to prevent recurrences of AP.Methods: We abstracted data from medical records of all Olmsted county residents who underwent cholecystectomy at Mayo Clinic for the management of presumed gallstone or idiopathic AP between 1990 and 2005 (n = 239). Based on (i) significantly elevated liver enzymes (≥threefold increase of alanine aminotransferase or aspartate aminotransferase) on day 1 and (ii) the presence of gallstones/sludge in the gall bladder, we categorized patients into 4 groups: A (i + ii), B (i but not ii), C (ii but not i), and D (neither i nor ii). Recurrence rates of AP after cholecystectomy were determined in all groups.Results: The median follow-up after cholecystectomy was 99 months (range, 8–220). AP recurred in 13 of 142 patients (9%) in group A, 1 of 17 patients (6%) in group B, 13 of 57 patients (23%) in group C, and 14 of 23 patients (61%) in group D (P < .0001 D vs all other groups and P = .001 C vs groups A and B). No difference was seen in recurrence rates in groups A vs B (P = 1.0). Recurrences were more frequent in patients with normal liver enzymes (A + B vs C + D; P = .000003) and in patients without sonographic evidence of gallstones/sludge (A + C vs B + D; P = .0008).Conclusion: When AP is associated with significantly elevated liver enzymes on day 1, recurrence rates after cholecystectomy are low (9%). However, postcholecystectomy recurrence rates of AP are high in those without such laboratory abnormalities (34%), especially in those without gall bladder stones/sludge (61%) on abdominal ultrasonography. Our results raise doubts about the efficacy of cholecystectomy to prevent recurrent AP in patients with the absence of either a significant elevation of liver tests on day 1 of AP or gallstones and/or sludge in the gall bladder on initial ultrasound examination.

Morphologic changes and prognosis of the respiratory tract epithelium in inhalation injury and their relationship with clinical manifestations

Li Ligen, Yang Hongming, Li Feng, Shen Chuanan, Hao Daifeng, Tuo Xiaoye — 2011-09-07

Background: We set out to observe the morphologic changes and determine prognosis based on airway epithelial injury after inhalation injury of varying severity using a fiberbronchoscope and to explore the relationship between the severity of epithelial injury and its clinical manifestation.Methods: Sixty burn patients with an inhalation injury underwent fiberoptic bronchoscopy. Morphologic changes of the airway epithelium were observed, and the inhalation injury was divided into 3 categories based on the severity of the epithelial injury: first-degree injury, in which the airway epithelium had slight hyperemia and edema; second-degree injury, in which obvious epithelial hyperemia and edema, epithelial erosion, or petechial hemorrhage was observes; and third-degree, in which the airway epithelium had necrosis and exfoliation. For all groups, chest radiographs were examined. The duration of ventilation was recorded.Results: Among 60 patients, 16 (27%) had first-degree injury, 33 (55%) had second-degree injury, and 11 (18%) had third-degree injury. Among this last group, 4 patients with epithelial exfoliation had airway hemorrhage. In this study, 38 of 60 (63%) patients presented with abnormal findings on lung radiographs and 9 of 60 (15%) developed pulmonary infections. The duration of ventilation averaged 2 days for second-degree injury and 14 days for third-degree injury. The recovery times for first-, second-, and third-degree injury were 7, 16, and 29 days, respectively.Conclusion: Fiberoptic bronchoscopy contributes to the accurate evaluation of tracheal epithelial injury severity. As the severity of inhalation injury increased, the clinical symptoms also increased. Severe complications (eg, bleeding and asphyxia caused by epithelial slough) may occur in patients with third-degree injury and should be closely observed by clinicians. The airway epithelium has a substantial potential for repair. Even if the airway epithelial injury is severe, the damaged epithelium will recover.

The impact of CD4+CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma

2011-10-05

Background: Hepatocellular carcinoma (HCC) is the most common liver cancer. Therapeutic results are usually unsatisfactory because liver tumors recur often. Immunologic factors may be related to the recurrence of HCC; however, this possibility is mentioned only rarely.Methods: Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs: group A (n = 8), diameter ≤3 cm; group B (n = 8), diameter >3 cm and ≤5 cm; and group C (n = 14), diameter >5 cm. T-lymphocytes from peripheral blood, nontumor liver tissue, and the HCC were analyzed.Results: The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups. CD25+ cells were increased in the tumor tissue in group C patients (range, 6–41%; median, 22.9%; P = .003), compared to group A patients. The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes (r = 0.556). These CD4+ CD25+ lymphocytes produced transforming growth factor-β and interferon-γ but not interleukin-10, and were anergic to plate-coated monoclonal antibodies (anti-CD3/anti-CD28). The characteristics of these antibodies were comparable to those of regulatory T cells. When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells, the proliferation of lymphocytes was inhibited.Conclusion: The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes. These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells.

The necessity of hepatic vein reconstruction after resection of cranial part of the liver and major hepatic veins in cirrhotic patients

2010-12-23

Background: The necessity of hepatic vein reconstruction (HVR) after resection of cranial part of the liver and major hepatic vein(s) in cirrhotic patients when residual liver is insufficient for a major hepatectomy remains unclear.Methods: Fifty-two cirrhotic patients who underwent resection of cranial part of the liver and hepatic vein(s) for liver neoplasms were divided retrospectively into 3 groups based on the volume of the congestive area of the remnant liver after hepatectomy: group A, 28 patients, the volume of the congestive area was ≤20% of the residual liver volume and underwent no HVR; group B, 7 patients, the volume of the congestive area was >20% of residual liver volume and underwent no HVR; and group C, 17 patients, in whom HVR was performed (the volume of the congestive area was >20% of residual liver volume in 16 and <20% in 1). Background characteristics and postoperative results were compared between the groups.Results: Although group C patients had a significantly longer operative time, their postoperative courses were similar to group A patients. Group B patients had a significantly longer postoperative hospital stay and a greater postoperative morbidity and 90-day mortality. No 90-day mortality ensued in the group A and C patients.Conclusion: In selected cirrhotic patients whose remnant liver is insufficient for major hepatectomy, HVR appears to be safe and desirable after resection of the cranial part of liver and hepatic vein when the volume of congestive area of liver remnant exceeds 20% of future residual liver volume.

Early cancer-related death after resection of hepatocellular carcinoma

2010-12-23

Background: Surgeons have attempted to prevent early cancer-related death after resection of hepatocellular carcinoma to identify risk factors associated with early death from hepatocellular carcinoma recurrence after liver resection.Methods: The study group comprised 350 patients who had undergone liver resection for hepatocellular carcinoma between 1997 and 2007. The preoperative risk factors for early death from intrahepatic recurrence (within 1 year after resection) were evaluated.Results: Fourteen (4%) patients died of intrahepatic recurrence in the first year after resection. Multivariate analyses identified the following risk factors for early cancer-related death: multiple tumors (odds ratio 10.4; 95% confidence interval, 2.42–44.3; P = .002), vascular invasion (odds ratio 10.1; 95% confidence interval 2.07–50; P = .004), serum alpha-fetoprotein level >20 ng/mL (odds ratio 9.52; 95% confidence interval 1.0–-84.2; P = .043), and tumor size ≥50 mm (odds ratio 4.80; 95% confidence interval 1.06–21.9; P = .042). Each of these factors was assigned a score of 1 point, and an algorithm was developed to predict the risk of early death. Outcomes did not differ significantly between patients with 3 or 4 points (P = .48) or between those with 1 or 2 points (P = .49). Patients who underwent liver resection could be stratified into the following distinct groups according to the point score and the associated 1-year survival rate and median survival (shown respectively): 0 points, 99%, and not yet; 1 or 2 points, 96%, and 68 months; and 3 or 4 points, 50%, and 12 months) (P < .0001).Conclusion: Even if hepatocellular carcinoma is resectable, patients with a score of 3 or 4 points may not be good candidates for liver resection.

Clinical impact of a macroscopically complete resection of colorectal cancer with peritoneal carcinomatosis

2010-12-23

Background: So far, few reports have focused on the clinicopathological features and patterns of recurrence after a complete resection of peritoneal carcinomatosis (PC) of colorectal origin. The purpose of the present study was to show the clinicopathological features of a macroscopically complete resected tumor and the pattern of recurrence after the curative resection of colorectal PC.Methods: In 153 patients with colorectal PC, 31 patients who underwent a complete resection of a synchronous primary lesion of a colorectal PC between 1998 and 2007 were assessed retrospectively.Results: Clinicopathological differences were observed in the tumor location, presence of extraperitoneal metastases, extent of PC, and presence of lymph node metastases between a macroscopically complete resection and noncomplete resection patients (P = .045, P < .0001, P < .001, and P = .039, respectively). Tumor recurrence after the complete resection of colorectal PC was observed in 24 patients (77.4%). The 5-year survival rate after complete resection was 36.0%. The survival rate in the macroscopically complete resection group was higher than in the incomplete resection group (P < .001). The 5-year intra- and extraperitoneal recurrence survival rates were 63.9% and 33.8%, respectively. No significant clinicopathological factors affected intraperitoneal recurrence-free survival. Conversely, a univariate analysis using the log-rank test revealed that extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence (P = .009 and P = .023, respectively). Eleven of 31 patients survived for 5 years after resection. Two of the 4 patients with liver metastases had received a hepatectomy.Conclusion: Although the 5-year survival rate after a macroscopically complete resection for colorectal PC approached 36.0%, 77.4% of patients developed intra- and extraperitoneal recurrence. Extended PC and presence of lymph node metastases were poor factors affecting extraperitoneal recurrence.

Outcomes of elective abdominal aortic aneurysm repair among the elderly: Endovascular versus open repair

Mehul V. Raval, Mark K. Eskandari — 2011-01-19

Background: National outcomes for elective abdominal aortic aneurysm (AAA) repair in elderly populations are needed. The purpose of this study was to analyze outcomes of endovascular (EVAR) and open surgical repair (OSR) of elective AAA among the elderly (≥80 years).Methods: Patients undergoing non emergent AAA repair between January 1, 2005 and December 31, 2008, were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Logistic regression models were used to compare risk-adjusted 30-day outcomes.Results: Of 7,936 patients identified, 2,034 (25.6%) were ≥80 years. Older patients were more likely to experience adverse 30-day outcomes as compared with patients <80 years: overall morbidity (17.4% vs 15.4%, OR 1.33, 95% CI 1.14–1.55) and mortality (2.6% vs 1.4%, OR 1.83, 95% CI 1.37–2.90). A majority (80.8%) of patients ≥80 years were treated with EVAR, which was associated with lesser overall morbidity (13.6% vs 33.2%, OR 2.64, 95% CI 2.02–3.45) and mortality (1.8% vs 6.1%, OR 3.37, 95% CI 1.92–5.91) as compared with OSR. Multivariable analysis showed that elderly patients undergoing OSR, as compared with EVAR, had a greater likelihood of infectious (OR 3.48, 95% CI 2.51–4.83), pulmonary (OR 5.70, 95% CI 3.87–8.41), cardiac (OR 5.60, 95% CI 2.57–12.22), and renal complications (1.96, 95% CI 1.13–3.38), greater requirements for blood transfusion (OR 5.66, 95% CI 2.65–12.09), and longer duration of stay (OR 10.64, 95% CI 7.95–14.23).Conclusion: Although elderly patients have worse outcomes compared with younger patients regardless of approach, endovascular repair among elderly patients is associated with less morbidity and mortality compared with open repair.

Primary leiomyosarcoma of the inferior vena cava: A 2-institution analysis of outcomes

Gary N. Mann, Lisa V. Mann, Edward A. Levine, Perry Shen — 2010-12-23

Background: Approximately 300 cases of leiomyosarcoma of the inferior vena cava (IVC) have been reported in the literature to date. In this study, we combined the experience from 2 institutions to provide additional clinical outcomes data.Methods: We performed a retrospective analysis from 1984 to 2009 that included 17 patients treated between the 2 institutions. Clinicopathologic data, surgical and adjuvant therapy, and survival outcomes were obtained.Results: The median age of patients in the study was 48 years. The tumor location was infrarenal in 8 patients, juxtarenal in 6, and suprahepatic in 2 patients; 7 patients had high-grade tumors. All patients underwent complete resection; the IVC was repaired primarily in 5 patients, ligated in 5, and reconstructed with a prosthetic tube graft in 7 patients. There was no perioperative mortality; 6 patients had complications. Median follow-up was 49 months; median survival had not been reached when this paper was written. The 5-year overall and disease -free survival were 56% and 37%, respectively. Of the 17 patients, 10 experienced disease recurrence and underwent numerous treatment modalities for these recurrences.Conclusion: Aggressive resection of primary leiomyosarcoma of the IVC can be performed safely and result in long-term survival, irrespective of IVC management. Despite high recurrence rates, no consensus yet exists regarding adjuvant treatment.

Macrophage migration inhibitory factor is a potential inducer of endothelial progenitor cell mobilization after flap operation

2011-01-03

Background: Endothelial progenitor cells (EPCs) promote angiogenesis and play an important role in tissue revascularization and wound healing. Yet, the exact stimuli and mechanisms for the mobilization remain understood poorly. Macrophage migration inhibitory factor (MIF), which is a structurally unique pleiotropic cytokine, has been suggested to play a role in EPC recruitment and thus was a target of this study.Methods: This study included 20 patients who underwent flap operation. Subjects were divided into 3 groups according to the pattern of flap applied. The number of circulating EPCs and serum levels of MIF or CXCL12 were determined at different time intervals. In vitro chemotaxis experiments using Transwell devices were carried out to test whether MIF promotes the chemotactic migration of EPCs. To underscore functionally the chemotactic potential of MIF toward EPCs in flap patients, the chemotactic effects of serum samples from all groups were also examined in the presence and absence of monoclonal anti-macrophage migration inhibitory factor and anti-CXCL12 antibodies on EPC recruitment using in vitro migration chambers.Results: In flap patients, the number of circulating EPCs and serum levels of MIF but not CXCL12 serum levels were increased markedly compared with preoperative levels at day 1 after operation, especially in the group of free microvascular flaps. Serum levels of CXCL12 in the flap patients were increased only significantly compared with the healthy control group. An analysis between EPCs and MIF revealed a significant correlation, whereas no correlation was observed for CXCL12. MIF exerted a dose-dependent, prochemotactic effect on isolated human EPCs, and serum samples from all flap patients promoted EPC migration. Importantly, this effect was blocked partially by anti-macrophage migration inhibitory factor and to a weaker extent by anti-CXCL12 antibodies.Conclusion: We conclude that MIF plays an important role in the mobilization of EPCs, which is dependent on the degree of ischemia. Enhancement by MIF of chemotactic EPCs migration in vitro underpins its proposed in vivo function.

Small intestine mucosal immune system response to injury and the impact of parenteral nutrition

2010-12-13

Background: Both humans and mice increase airway immunoglobulin A (IgA) after injury. This protective response is associated with TNF-α, IL-1β, and IL-6 airway increases and in mice is dependent upon these cytokines as well as enteral feeding. Parenteral nutrition (PN) with decreased enteral stimulation (DES) alters gut barrier function, decreases intestinal IgA, and decreases the principal IgA transport protein pIgR. We investigated the small intestine (SI) IgA response to injury and the role of TNF-α, IL-1β, IL-6, and PN/DES.Methods: Expt 1: Murine kinetics of SI washing fluid (SIWF) IgA; SI, SIWF and serum TNF-α, IL-1β, and IL-6, was determined by ELISA from 0 to 8 hours after a limited surgical stress injury (laparotomy and neck incisions). Expt 2: Mice received chow or PN/DES before injury and SIWF IgA and SI pIgR levels were determined at 0 and 8 hours. Expt 3: Mice received PBS, TNF-α antibody, or IL-1β antibody 30 minutes before injury to measure effects on the SIWF IgA response. Expt 4: Mice received injury or exogenous TNF-α, IL-1β, and IL-6 to measure effects on the SIWF IgA response.Results: Expt 1: SIWF IgA levels increased significantly by 2 hours after injury without associated increases in TNF-α or IL-1β whereas IL-6 was only increased at 1 hour after injury. Expt 2: PN/DES significantly reduced baseline SIWF IgA and SI pIgR and eliminated their increase after injury seen in Chow mice. Expt 3: TNF-α and IL-1β blockade did not affect the SIWF IgA increase after injury. Expt 4: Exogenous TNF-α, IL-1β, and IL-6 increased SIWF IgA similarly to injury.Conclusion: The SI mucosal immune responds to injury or exogenous TNF-α, IL-1β, and IL-6 with an increase in lumen IgA, although it does not rely on local SI increases in TNF-α or IL-1β as it does in the lung. Similar to the lung, the IgA response is eliminated with PN/DES.

Arginase inhibition promotes wound healing in mice

Sandra L. Kavalukas, Aarti R. Uzgare, Trinity J. Bivalacqua, Adrian Barbul — 2011-10-05

Objective: Arginase plays important regulatory roles in polyamine, ornithine, and nitric oxide syntheses. However, its role in the healing process has not been delineated. In this study, we used a highly potent and specific inhibitor of arginase, namely 2(S)-amino-6-boronohexanoic acid NH4 (ABH) to evaluate the role of arginase function in wound healing.Materials and Methods: ABH or saline was applied topically to full thickness, dorsal, excisional wounds in C57BL/6 mice every 8 hours for 14 days post surgery and the rate of wound closure was estimated planimetrically. Wound tissue was harvested from mice sacrificed on postoperative days 3 and 7 and examined histologically. The extent of epithelial, connective, and granulation tissue present within the wound area was estimated histomorphometrically. The effect of ABH on wound arginase activity, production of nitric oxide metabolites (NOx), and presence of smooth muscle actin positive cells (myofibroblasts) was evaluated.Results: While arginase activity was inhibited in vivo, the rate of wound closure significantly increased 7 days post-surgery, (21 ± 4%: P < .01; Student t test) in ABH treated animals. This was accompanied by an early increase in wound granulation tissue and accumulation of NOx followed by enhanced re-epithelialization and localization of myofibroblasts beneath the wound epithelium.Conclusion: Arginase inhibition improves excisional wound healing and may be used to develop therapeutics for early wound closure.

The angiogenic factor Del1 prevents apoptosis of endothelial cells through integrin binding

2011-09-07

Background: Del1 is a secreted protein that is expressed in the endothelium during development and can stimulate angiogenesis through integrin binding and signaling. We were interested in the specific effects of del1 on endothelial cell biology to gain insight into its biologic role during angiogenesis.Methods: Primary endothelial cells were treated with a variety of inducers of apoptosis and anoikis followed by assays for numbers of apoptotic cells, and harvest of total protein for immunoblot analysis.Results: Del1 prevented endothelial cell apoptosis in response to TNFα/IFNγ, etoposide, and anoikis, but had no effect on proliferation. The anti-apoptotic effect was mediated specifically through binding of integrin αvβ3 by the RGD motif. FAK/ERK and Akt signaling were both necessary to mediate the anti-apoptotic effect of Del1 with the exception of anoikis, which required only Akt activation.Conclusion: Del1 has been previously shown to promote vascular smooth muscle cell adhesion, migration, and proliferation. We demonstrate here that Del1 prevented apoptosis of endothelial cells in cell culture through integrin binding without any effect on proliferation.

Roles of thymidylate synthase and dihydropyrimidine dehydrogenase expression in blood as predictors of response to multimodal therapy in esophageal cancer

2011-10-10

Background: Thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) RNA expression in peripheral blood was examined as a noninvasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus.Methods: Blood samples were drawn from 29 patients with esophageal cancer (10 squamous cell carcinomas and 19 adenocarciomas) before neoadjuvant radiochemotherapy. After extraction of cellular tumor RNA from blood samples, quantitative expression analysis of TS and DPD was performed with quantitative real-time reverse-transcription polymerase chain reaction.Results: Twenty of 29 (68%) of patients had a minor histopathologic response, and 9 of 29 (32%) had a major response to neadjuvant radiochemotherapy. RNA expression in the blood of patients was detectable for TS in 86%, for DPD in 97%, and in 100% for β-actin. No significant associations were detected between TS and DPD expression levels and clinical variables of the patients. A high expression level for TS was associated with a minor response to neoadjuvant treatment (P = .046), while there was no significant association between DPD and response to therapy. Combined analysis of TS and DPD expression increased the specificity for the prediction of response to 100%. No major responder to therapy had high expression levels for both genes in their peripheral blood.Conclusion: Quantitation of TS and DPD in peripheral blood may be a highly specific analysis to identify a subset of patients who do not respond to neoadjuvant radiochemotherapy and may therefore prevent expensive, noneffective, and potentially harmful therapies in a substantial number of patients with esophageal cancer.

Neutralization of interleukin-10 or transforming growth factor-β decreases the percentages of CD4+CD25+Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival

2011-10-10

Objectives: To investigate the role of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in septic conditions, and to examine the potential of targeting them for the treatment of sepsis.Background: Sepsis-induced immunosuppression has long been considered a factor in late mortality of patients with sepsis. Although Tregs are central to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the late stages of sepsis.Methods: Peripheral blood mononuclear cells (MNCs) in septic patients and liver or spleen MNCs collected after a cecal ligation and puncture (CLP) model in C57BL/6 mice were examined to evaluate the roles of Tregs and the correlation of transforming growth factor (TGF)-β or interleukin (IL)-10 with their activity. We next examined the effects of neutralization of TGF-β or IL-10 on the percentages of Tregs in CD4+ T cells and the survival rates of septic mice.Results: The percentages of Tregs in peripheral blood lymphocytes were significantly increased in patients with sepsis, and there was a significantly positive correlation between serum IL-10 levels and the percentage of Tregs. CLP injury increases the percentages of Tregs in the CD4+ T cells in the spleen, and there was a significantly positive correlation between the percentages of Tregs and the serum IL-10 or TGF-β levels. The neutralization of TGF-β or IL-10 decreased the percentages of Tregs in CD4+ T cells, restored the percentages of CD4+ T cells in spleen MNCs, and improved survival rates in septic mice.Conclusion: We found an increase in the percentages of Tregs in peripheral blood circulating CD4+ T cells from patients with sepsis, and in splenic MNCs from septic mice, and observed that regulation of Tregs by neutralizing IL-10 or TGF-β might represent a novel strategy for treating the immunosuppressive conditions in sepsis.

Associations between promoter polymorphism -106A/G of interleukin-11 receptor alpha and papillary thyroid cancer in Korean population

2011-10-10

Background: The interleukin11 (IL11) and IL11 receptor alpha (IL11RA) are involved in cellular growth, differentiation, invasiveness, and tumor progression in several tumors. We investigated whether coding single nucleotide polymorphisms (cSNPs) of IL11 and promoter SNP IL11RA would contribute to the development of papillary thyroid cancer (PTC). We also assessed the relationships between IL11 and IL11RA SNPs and the clinicopathologic characteristics of PTC.Methods: One coding SNP, designated as rs1126757, Ala82Ala, in IL11 and one promoter SNP, designated as rs1061758, −106A/G, in IL11RA were genotyped using direct sequencing in 94 patents with PTC and 213 patients without PTC (controls). Genetic data were analyzed using commercially available software. The patients with PTC were dichotomized and compared with respect to clinicopathologic characteristics of PTC.Results: We found an association between PTC and the coding SNP(rs1061758) in IL11RA (codominant model 1 [G/G vs A/G], odds ratio [OR] = 2.91, 95% confidence interval [CI], 1.44–5.89; P = .003; codominant model 2 [G/G vs A/A], OR = 2.95, 95% CI, 1.30–6.72; P = .01; and dominant model, OR = 2.92, 95% CI, 1.47–5.80; P = .002). Moreover, SNP rs1061758 in IL11RA was associated with the multifocality of PTC (codominant model 2 [A/A vs G/G], OR = 9.56, 95% CI, 1.77–51.69; P = .009; and recessive model, OR = 7.22, 95% CI, 1.72–30.3; P = .007). Genotype and allele analyses of SNP variant rs1126757 in IL11 revealed no statistically significant differences between patients with PTC and controls.Conclusion: Our results suggest that an IL11RA promoter polymorphism — rs1061758 — may be associated with the risk of PTC in the Korean population. In addition, rs1061758 might be related to the multifocality of PTC.

Conditional and specific inhibition of NF-κB in mouse pancreatic β cells prevents cytokine-induced deleterious effects and improves islet survival posttransplant

Jonathan S. Rink, Xiaojuan Chen, Xiaomin Zhang, Dixon B. Kaufman — 2011-10-10

Background: Islets are susceptible to damage by proinflammatory cytokines via activation of transcription factor NF-κB. We hypothesized that inhibition of NF-κB activity will decrease cytokine–mediated β-cell injury and improve islet transplant functional outcome.Methods: We created a transgenic mouse expressing a degradation resistant N-terminally deleted IκBα (ΔNIκBα) under the control of a commercially available tetracycline-controlled transcriptional activation system using a rat insulin promoter. Isolated islets from transgenic and control mouse strains were exposed to cytokines in vitro and assayed or transplanted.Results: Western blot analysis showed that ΔNIκBα was significantly increased with doxycycline treatment. Cytokine-induced NF-κB activation was significantly decreased in transgenic (0.065 ± 0.013 absorbance value/μg protein) vs control islets (0.128 ± 0.006; P < .05). Suppression of cytokine-mediated NF-κB activity decreased expression of inducible nitric oxide synthase, monocyte chemoattractant protein-1, and interferon-γ inducible protein-10 RNA transcripts, and significantly decreased nitric oxide production in transgenic islets (0.084 ± 0.043 μM/μg protein) vs controls (0.594 ± 0.174; P < .01). The insulin stimulation index in islets exposed to cytokines was higher in transgenic vs controls (1.500 ± 0.106 vs 0.800 ± 0.098; P < .01). Syngeneic transplants of a marginal mass of intraportally infused transgenic islets resulted in a reversion to euglycemia in 69.2% of diabetic recipients at a mean of 7.8 ± 1.1 days vs 35.7% of control islet recipients reverting at a mean of 15.8 ± 2.9 days (P < .05).Conclusion: Conditional and specific suppression of NF-κB activity in β cells protected islets from cytokine-induced dysfunction in vitro and in vivo. These results provide a proof of principle that inhibition of NF-κB activity in donor islets enhances function and improves the outcome of islet transplantation.

A 1.3-cm carcinoid tumor of the minor duodenal papilla with superior mesenteric lymph node metastases

2010-09-27

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Hereditary diffuse gastric cancer: The always-forgotten Meckel’s diverticulum

2012-02-01

The aim of prophylactic surgery is to remove as much of the at-risk tissue as possible to reduce the chances of developing cancer in the at risk tissue. This point is made clear by Pandalai et al in their study of patients with CDH1 mutations, where total gastrectomy is performed to excise all the at risk gastric mucosa. For this reason, partial gastrectomy is contraindicated in these patients, and the total gastrectomy is performed with a resection line across the distal esophagus to ensure no gastric cardia mucosa is left behind.

Erratum

2012-02-01

“A prospective study evaluating the accuracy of using combined clinical factors and candidate diagnostic markers to refine the accuracy of thyroid fine needle aspiration biopsy” by Aarti Mathur, Julie Weng, Willieford Moses, Seth M. Steinberg, Reza Rahabari, Mio Kitano, Elham Khanafshar, Britt-Marie Ljung, Quan-Yang Duh, Orlo H. Clark, and Electron Kebebew, which appeared in Surgery, Vol. 148, No. 6:1170-7, 2010 was published with an incorrect spelling of an author name. The correct spelling for Reza Rahabari should be Reza Rahbari. Surgery and the authors apologize for the oversight.

2012-02-01

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2012-02-01

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2012-02-01

Surgery

Cover 1

Error training: Missing link in surgical education

Creating a learning healthcare system in surgery: Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP) at 5 years

Prevention of medical accidents caused by defective surgical instruments

Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases

Rates and patterns of death after surgery in the United States, 1996 and 2006

Use of omentum or falciform ligament does not decrease complications after pancreaticoduodenectomy: Nationwide survey of the Japanese Society of Pancreatic Surgery

Prophylactic central lymph node dissection for clinically node-negative papillary thyroid microcarcinoma: Influence on serum thyroglobulin level, recurrence rate, and postoperative complications

Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: A population-based study

Morphologic changes and prognosis of the respiratory tract epithelium in inhalation injury and their relationship with clinical manifestations

The impact of CD4+CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma

The necessity of hepatic vein reconstruction after resection of cranial part of the liver and major hepatic veins in cirrhotic patients

Early cancer-related death after resection of hepatocellular carcinoma

Clinical impact of a macroscopically complete resection of colorectal cancer with peritoneal carcinomatosis

Outcomes of elective abdominal aortic aneurysm repair among the elderly: Endovascular versus open repair

Primary leiomyosarcoma of the inferior vena cava: A 2-institution analysis of outcomes

Macrophage migration inhibitory factor is a potential inducer of endothelial progenitor cell mobilization after flap operation

Small intestine mucosal immune system response to injury and the impact of parenteral nutrition

Arginase inhibition promotes wound healing in mice

The angiogenic factor Del1 prevents apoptosis of endothelial cells through integrin binding

Roles of thymidylate synthase and dihydropyrimidine dehydrogenase expression in blood as predictors of response to multimodal therapy in esophageal cancer

Neutralization of interleukin-10 or transforming growth factor-β decreases the percentages of CD4+CD25+Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival

Associations between promoter polymorphism -106A/G of interleukin-11 receptor alpha and papillary thyroid cancer in Korean population

Conditional and specific inhibition of NF-κB in mouse pancreatic β cells prevents cytokine-induced deleterious effects and improves islet survival posttransplant

A 1.3-cm carcinoid tumor of the minor duodenal papilla with superior mesenteric lymph node metastases

Hereditary diffuse gastric cancer: The always-forgotten Meckel’s diverticulum

Erratum

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