Intraoperative Adverse Events in Abdominal Surgery: What Happens in the Operating Room Does Not Stay in the Operating Room.

OBJECTIVE: We sought to assess the impact of intraoperative adverse events (iAEs) on 30-day postoperative mortality, 30-day postoperative morbidity, and postoperative length of stay (LOS) among patients undergoing abdominal surgery. We hypothesized that iAEs would be associated with significant increases in each outcome. SUMMARY OF BACKGROUND DATA: The relationship between iAEs and postoperative clinical outcomes remains largely unknown. METHODS: The 2007 to 2012 institutional ACS-NSQIP and administrative databases for abdominal surgeries were matched then screened for iAEs using the Agency for Healthcare Research and Quality's 15 Patient Safety Indicator, "Accidental Puncture/Laceration". Each chart flagged during the initial screen was then manually reviewed to confirm whether an iAE occurred. Univariate then multivariable logistic regression models were constructed to assess the independent impact of iAEs on 30-day mortality, 30-day morbidity, and prolonged (≥7 days) postoperative LOS, controlling for preoperative/intraoperative variables (eg, age, comorbidities, ASA, wound classification), procedure type (eg, laparoscopic vs open, intestinal, foregut, hepatopancreaticobiliary vs abdominal wall procedure), and complexity (eg, adhesions; relative value units). Propensity score analyses were conducted with each iAE patient matched with 5 non-iAE patients. Sensitivity analyses were performed. RESULTS: A total of 9288 cases were included; 183 had iAEs. Most iAEs consisted of bowel (44%) or vessel (29%) injuries and were addressed intraoperatively (92%). In multivariable analyses, iAEs were independently associated with increased 30-day mortality [OR = 3.19, 95% confidence interval (CI) 1.52-6.71, P = 0.002], 30-day morbidity (OR = 2.68, 95% CI 1.89-3.81, P < 0.001), and prolonged postoperative LOS (OR = 1.85, 95% CI 1.27-2.70, P = 0.001). Postoperative complications associated with iAEs included deep/organ-space surgical site infection (OR = 1.94, 95% CI 1.20-3.14), P = 0.007), sepsis (OR = 2.14, 95% CI 1.32-3.47, P = 0.002), pneumonia (OR = 2.18, 95% CI 1.11-4.26, P = 0.023), and failure to wean ventilator (OR = 3.88, 95% CI 2.17-6.95, P < 0.001). Propensity score matching confirmed these findings, as did multiple sensitivity analyses. CONCLUSIONS: iAEs are independently associated with substantial increases in postoperative mortality, morbidity, and prolonged LOS. Quality improvement efforts should focus on iAE prevention, mitigation of harm after iAEs occur, and risk/severity-adjusted iAE tracking and benchmarking.

Adverse Events Postoperatively Had No Impact on Long-Term Survival of Patients Treated with Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy for Appendiceal Cancer with Peritoneal Metastases.

BACKGROUND: Appendiceal cancer most commonly metastasizes to the peritoneum. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is the standard of care for appendiceal cancer with peritoneal metastases. Adverse events postoperatively have been associated with reduced survival. We analyzed clinical outcomes, including complications after CRS and HIPEC in patients with appendiceal cancer, in a recent cohort of patients to identify prognostic factors. METHODS: Patients undergoing CRS with HIPEC for appendix cancer with peritoneal metastases between January 2007 and December 2009 were identified. Prospectively collected data were analyzed, including preoperative, intraoperative, and postoperative variables, and multivariate Cox regression models were developed to identify factors independently predicting overall survival (OS). RESULTS: A total of 133 consecutive patients with a median age of 51 years were analyzed; 53.4 % were female. Pre-, intra-, and postoperative clinical variables analyzed for their impact on survival included sex, age, prior surgical score, Peritoneal Cancer Index, completeness of cytoreduction score, histology, lymph node metastases, operative time, blood transfusion, fresh frozen plasma transfusion, perioperative chemotherapy, postoperative complications, length of hospitalization, and disease recurrence. OS at 5 years was 74.4 %, and 5-year recurrence-free survival (RFS) of patients with a complete cytoreduction (CC ≤ 1) was 65.5 %. Factors independently predicting shorter survival included peritoneal mucinous adenocarcinoma (PMCA) histology (hazard ratio [HR] 15.2, 95 % confidence interval [CI] 3.38-69.0), lymph node metastasis (HR 3.82, 95 % CI 1.13-12.8), and incomplete cytoreduction [CC3; HR 13.7, 95 % CI 3.18-59.1). An incomplete cytoreduction was associated with the PMCA variant (p < 0.001). Postoperative complications grade I/II (p = 0.113) and grade III/IV (p = 0.669) had no impact on OS in multivariate analysis. CONCLUSION: CRS with HIPEC can achieve long-term survival for patients with appendix cancer with peritoneal metastases. Histologic subtype, lymph node metastasis, and incomplete cytoreduction are the significant predictors of OS. Postoperative adverse events had no impact on survival.

The nature, patterns, clinical outcomes, and financial impact of intraoperative adverse events in emergency surgery.

BACKGROUND: Little is known about intraoperative adverse events (iAEs) in emergency surgery (ES). We sought to describe iAEs in ES and to investigate their clinical and financial impact. METHODS: The 2007 to 2012 administrative and American College of Surgeons-National Surgical Quality Improvement Program databases at our tertiary academic center were: (1) linked, (2) queried for all ES procedures, and then (3) screened for iAEs using the ICD-9-CM-based Patient Safety Indicator "accidental puncture/laceration". Flagged cases were systematically reviewed to: (1) confirm or exclude the occurrence of iAEs (defined as inadvertent injuries during the operation) and (2) extract additional variables such as procedure type, approach, complexity (measured by relative value units), need for adhesiolysis, and extent of repair. Univariate and multivariate analyses were performed to assess the independent impact of iAEs on 30-day morbidity, mortality, and hospital charges. RESULTS: Of a total of 9,288 patients, 1,284 (13.8%) patients underwent ES, of which 23 had iAEs (1.8%); 18 of 23 (78.3%) of the iAEs involved the small bowel or spleen, 10 of 23 (43.5%) required suture repair, and 8 of 23 (34.8%) required tissue or organ resection. Compared with those without iAEs, patients with iAEs were older (median age 62 vs 50; P = .04); their procedures were more complex (total relative value unit 46.7, interquartile range [27.5 to 52.6] vs 14.5 [.5 to 30.2]; P < .001), longer in duration (>3 hours: 52% vs 8%; P < .001), and more often required adhesiolysis (39.1% vs 13.5% P = .001). Patients with iAEs had increased total charges ($31,080 vs $11,330, P < .001), direct charges ($20,030 vs $7,387, P < .001), and indirect charges ($11,460 vs $4,088, P < .001). On multivariable analyses, iAEs were independently associated with increased 30-day morbidity (odds ratio, 3.56 [CI, 1.10 to 11.54]; P = .03) and prolonged postoperative length of stay (LOS; LOS >7 days; odds ratio, 5.60 [1.54 to 20.35]; P = .01]. A trend toward increased mortality did not reach statistical significance. CONCLUSIONS: In ES, iAEs are independently associated with significantly higher postoperative morbidity and prolonged LOS.

Additional Imaging in Alert Trauma Patients with Cervical Spine Tenderness and a Negative Computed Tomographic Scan: Is it Needed?

BACKGROUND: The value of additional imaging in clearing the cervical spine (C-spine) of alert trauma patients with tenderness on clinical exam and a negative computed tomographic (CT) scan is still unclear. METHODS: All adult trauma patients with a Glasgow Coma Scale of 15, C-spine tenderness in the absence of neurologic signs, and a negative C-spine CT were included. The study period extended from September 2011 to June 2012. C-spine CT scans were interpreted in detail and considered negative in the absence of any findings indicating bony, ligamentous, or soft tissue injury around the C-spine. The incidence of C-spine injury was evaluated using early (<24 h) repeat physical examination, MRI, and/or flexion-extension films. RESULTS: Of 2015 patients with a C-spine CT, 383 (19 %) fulfilled the inclusion criteria. The median age was 43 (IQR: 30-53) and 44.7 % were female. Thirty-six patients (9.4 %) underwent MRI (3.7 %), flexion-extension imaging (5.2 %), or both (0.5 %), with no significant injuries identified and subsequent removal of the collar allowed. The remaining patients were clinically cleared within 24 h of presentation. None of the patients developed neurological signs following removal of the collar. On bivariate analysis, no variable except for evaluation by trauma surgery was associated with performance of additional imaging. CONCLUSION: C-spine precautions can be withdrawn without additional imaging in most blunt trauma patients with C-spine tenderness but negative neurologic evaluation and C-spine CT. Focus should be placed on the detailed and comprehensive interpretation of the C-spine CT.

Perioperative Blood Transfusion and the Prognosis of Pancreatic Cancer Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Perioperative blood transfusion (PBT) is common in pancreatic surgery. Recent studies have suggested that PBT may be associated with worse long-term outcomes. METHODS: A systematic review and meta-analysis of studies comparing long-term clinical outcomes of cancer patients undergoing curative-intent pancreatic surgery with regard to occurrence of PBT was performed. RESULTS: A total of 23 studies (4339 patients) were included in the systematic review, and 19 studies (3646 patients) were included in the meta-analysis. Nearly half (45.8 %) of all patients were female (range 25-60 %), and median age ranged from 59 to 72 years. About half (46.5 %, range 19-72 %) of the patients were transfused. Most had pancreatic ductal adenocarcinoma (69.5 %), while others had ampullary carcinoma (15.0 %), cholangiocarcinoma (7.4 %), or exocrine tumors of pancreas (8.1 %). Most (91.1 %) underwent pancreaticoduodenectomy, while the remaining patients underwent a total or distal pancreatectomy. The 5-year overall survival for all patients ranged from 0 to 65 %. Thirteen and nine of 19 studies reported a detrimental effect of PBT on survival on univariable and multivariable analysis, respectively. Overall, PBT was associated with shorter overall survival (pooled odds ratio 2.43, 95 % confidence interval 1.90-3.10); this finding was reproduced in sensitivity analysis. CONCLUSIONS: Patients receiving PBT had significantly lower 5-year survival after curative-intent pancreatic surgery. Further research should focus on implementing guidelines for and discerning factors associated with the poor outcomes after PBT.

Intraoperative Adverse Events: Risk Adjustment for Procedure Complexity and Presence of Adhesions Is Crucial.

BACKGROUND: Benchmarking the quality of intraoperative care by comparing the rates of intraoperative adverse events (iAEs) necessitates adequate risk adjustment. We sought to identify the patient- and procedure-related risk factors for iAEs. STUDY DESIGN: Our 2007 to 2012 institutional American College of Surgeons NSQIP and administrative databases were linked and then screened for iAEs using the Patient Safety Indicator "Accidental Puncture/Laceration." Intraoperative adverse events were confirmed by systematic review of medical records. Comorbidities were assessed using American College of Surgeons NSQIP variables. Adhesiolysis was determined using CPT codes for lysis of adhesions. Operative complexity was determined using relative value units. Multivariable models were constructed to identify independent predictors of iAEs. Sensitivity analyses were performed in uniform samples of operations. RESULTS: Of 9,292 patients, 218 iAEs were confirmed in 183 patients. Median patient age was 56 years old and 54% were female. Compared with patients without iAEs, iAE patients were older (median 61 vs 56 years; p < 0.001), more functionally dependent (9% vs 5%; p = 0.028), and had higher American Society of Anesthesiologists class (≥3 in 45% vs 35%; p = 0.004); their procedures were more complex (median relative value units 29 vs 23; p < 0.001), more likely open (48% vs 21%; p < 0.001), and more often required adhesiolysis (44% vs 18%; p < 0.001). In multivariable analyses, adhesiolysis (odds ratio = 2.34; 95% CI, 1.71-3.21; p < 0.001), higher operative complexity (third vs first relative value units quartile: odds ratio = 3.36; 95% CI, 1.66-6.78; p < 0.001; fourth vs first quartile: odds ratio = 5.97; 95% CI, 3.01-11.86; p < 0.001), and open surgical approach (odds ratio = 2.04; 95% CI, 1.39-3.01; p < 0.001) independently predicted iAEs. Sensitivity analyses confirmed adhesiolysis and higher operative complexity as independent iAE predictors. CONCLUSIONS: Adhesiolysis and higher operative complexity predict an increased risk for iAE. Attempts to benchmark the quality of intraoperative care need to adequately risk adjust for these factors.

Morbidity related to concomitant adhesions in abdominal surgery.

BACKGROUND: We sought to assess the independent effect of concomitant adhesions (CAs) on patient outcome in abdominal surgery. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program data, we created a uniform data set of all gastrectomies, enterectomies, hepatectomies, and pancreatectomies performed between 2007 and 2012 at our tertiary academic center. American College of Surgeons National Surgical Quality Improvement Program data were supplemented with additional variables (e.g., procedure complexity-relative value unit). The presence of CAs was detected using the Current Procedural Terminology codes for adhesiolysis (44005, 44180, 50715, 58660, and 58740). Cases where adhesiolysis was the primary procedure (e.g., bowel obstruction) were excluded. Multivariable logistic regression analyses were performed to assess the independent effect of CAs on 30-d morbidity and mortality, while controlling for age, comorbidities and the type/complexity/approach/emergency nature of surgery. RESULTS: Adhesiolysis was performed in 875 of 5940 operations (14.7%). Operations with CAs were longer (median duration 3.2 versus 2.7 h, P < 0.001), more complex (median relative value unit 37.5 versus 33.4, P < 0.001), performed in sicker patients (American Society for Anesthesiologists class ≥3 in 49.9% versus 41.2%, P < 0.001), and harbored higher risk for inadvertent enterotomies (3.0% versus 0.9%, P < 0.001). In multivariable analyses, CAs independently predicted higher morbidity (adjusted odds ratio [OR], 1.35; 95% confidence interval, 1.13-1.61, P = 0.001). Specifically, CAs independently correlated with superficial and deep or organ-space surgical site infections (OR = 1.42 (1.02-1.86), P = 0.036; OR = 1.47 (1.09-1.99), P = 0.013, respectively), and prolonged postoperative hospital stay (≥7 d, OR = 1.34 [1.11-1.61], P = 0.002). No difference in 30-d mortality was detected. CONCLUSIONS: CAs significantly increase morbidity in abdominal surgery. Risk adjusting for the presence of adhesions is crucial in any efforts aimed at quality assessment and/or benchmarking of abdominal surgery.

Opening Pandora's box: understanding the nature, patterns, and 30-day outcomes of intraoperative adverse events.

BACKGROUND: Little evidence exists regarding the characteristics of intraoperative adverse events (iAEs). METHODS: Administrative data, the American College of Surgeons - National Surgical Quality Improvement Project, and systematic review of operative reports were used to confirm iAEs in abdominal surgery patients. Standard American College of Surgeons - National Surgical Quality Improvement Project data were supplemented with variables including injury type/organ, phase of operation, adhesions, repair type, and intraoperative consultations. RESULTS: Two hundred twenty-seven iAEs (187 patients) were confirmed in 9,292 patients. Most common injuries were enterotomies during intestinal surgery (68%) and vessel injuries during hepatopancreaticobiliary surgery (61%); 108 iAEs (48%) specifically occurred during adhesiolysis. A third of the iAEs required organ/tissue resection or complex reconstruction. Because of iAEs, 20 intraoperative consults (11%) were requested and 9 of the 66 (16%) laparoscopic cases were converted to open. Thirty-day mortality and morbidity were 6% and 58%, respectively. The complications included perioperative transfusions (36%), surgical site infection (19%), systemic sepsis (13%), and failure to wean off the ventilator (12%). CONCLUSIONS: iAEs commonly occur in reoperative cases requiring lysis of adhesions and possibly lead to increased patient morbidity. Understanding iAEs is essential to prevent their occurrence and mitigate their adverse effects.

Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis.

IMPORTANCE: Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. OBJECTIVE: To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. DATA SOURCES: The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. STUDY SELECTION: Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. DATA EXTRACTION AND SYNTHESIS: Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. RESULTS: Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). CONCLUSIONS AND RELEVANCE: The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.

Derivation and validation of a novel severity classification for intraoperative adverse events.

BACKGROUND: There is currently no systematic approach to evaluating the severity of intraoperative adverse events (iAEs). STUDY DESIGN: A 3-phase project was designed to develop and validate a novel severity classification scheme for iAEs. Phase 1 created the severity classification using a modified Delphi process. Phase 2 measured the classification's internal consistency by calculating inter-rater reliability among 91 surgeons using standardized iAEs scenarios. Phase 3 measured the classification's construct validity by testing whether major iAEs (severity class ≥3) correlated with worse 30-day postoperative outcomes compared with minor iAEs (severity class <3). This was achieved by creating a matched database using American College of Surgeons NSQIP and administrative data, querying for iAEs using the Patient Safety Indicator #15 (Accidental Puncture/Laceration), and iAE confirmation by chart review. RESULTS: Phase 1 resulted in a 6-point severity classification scheme. Phase 2 revealed an inter-rater reliability of 0.882. Of 9,292 patients, phase 3 included 181 confirmed with iAEs. All preoperative/intraoperative variables, including demographics, comorbidities, type of surgery performed, and operative length, were similar between patients with minor (n = 110) vs major iAEs (n = 71). In multivariable logistic analysis, severe iAEs correlated with higher risks of any postoperative complication (odds ratio [OR] = 3.8; 95% CI, 1.9-7.4; p < 0.001), surgical site infections (OR = 3.7; 95% CI, 1.7-8.2; p = 0.001), systemic sepsis (OR = 6.0; 95% CI, 2.1-17.2; p = 0.001), failure to wean off the ventilator (OR = 3.2; 95% CI, 1.2-8.9; p = 0.022), and postoperative length of stay ≥7 days (OR = 3.0; 95% CI, 1.5-5.9; p = 0.002). Thirty-day mortalities were similar (4.5% vs 7.1%; p = 0.46). CONCLUSIONS: We propose a novel iAE severity classification system with high internal consistency and solid construct validity. Our classification scheme might prove essential for benchmarking quality of intraoperative care across hospitals and/or individual surgeons.

Treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma: a national perspective.

BACKGROUND: Surgery remains the only potentially curative option for patients with hepatocellular carcinoma (HCC) and fibrolamellar carcinoma (FLC). We sought to investigate the differences over time in surgically managed FLC compared with conventional HCC using population-based data. STUDY DESIGN: Using SEER data, we identified 7,225 patients with surgically managed FLC or HCC from 1986 to 2008. We examined differences in clinicopathologic and surgical factors associated with long-term survival. RESULTS: Of the 7,225 patients, the majority had HCC (n = 7,135; 99%) vs FLC (n = 90; 1%). Patients with FLC were younger (25 years vs 59 years) and more often were women (44% vs 27%) than patients with HCC (both p < 0.001). Regional disease was more common among patients with FLC (42.2%) vs patients with HCC (22.1%) (p < 0.001). More than one-third of patients with FLC (36.9%) were operatively managed with a hemihepatectomy compared with patients with HCC, who were more often managed with a liver transplant (p < 0.001). On univariable analysis, there was a marked difference in overall survival, with patients with FLC surviving a median of 75 months vs 43 months for HCC (hazard ratio [HR]: 0.59; p = 0.001). There was a marked difference in survival when patients were stratified by localized (FLC, 78 months vs HCC, 49 months; p = 0.012) vs regional disease (FLC, 46 months vs HCC, 23 months; p = 0.002. CONCLUSIONS: Patients with FLC have many clinicopathologic features that are different from those of patients with HCC, including younger age and female sex. Despite a higher likelihood of advanced disease at the time of diagnosis, surgically treated FLC patients had better long-term outcomes than patients with conventional HCC.

Recurrence patterns and prognostic factors in patients with hepatocellular carcinoma in noncirrhotic liver: a multi-institutional analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) primarily affects patients with a cirrhotic liver. Reports on the characteristics of patients with HCC in noncirrhotic liver, as well as predictors of recurrence and survival, are scarce. METHODS: Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic liver were identified from three major hepatobiliary centers. Clinicopathological characteristics were analyzed and independent predictors of recurrence and overall survival were identified using Cox proportional hazards models. RESULTS: Median patient age was 58 years and 77 % were male. Most patients had a solitary (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The majority of patients (96 %) underwent liver resection (microscopically negative margins in 94 %), whereas a few had transarterial chemoembolization or transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1- and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4), macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR = 1.9), or intrahepatic metastases (HR = 2.59) were independently associated with shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall survival was 86.9, and 54.5 %, respectively. Tumor size ≥5 cm (HR = 2.27), macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite lesions (HR = 2.18) were independently associated with shorter overall survival, whereas an intact tumor capsule showed a protective effect (HR = 0.51). CONCLUSIONS: Following resection of HCC in the setting of no cirrhosis, more than one-half of patients were alive after 5 years. However, even among patients with no cirrhosis, recurrence was common. Factors associated with RFS and overall survival included tumor characteristics, such as tumor capsule, satellite lesions, and vascular invasion.

Local therapies for hepatic metastases.

The liver is one of the most common sites for metastatic disease, and optimal management of hepatic metastases often requires a multidisciplinary approach. Most commonly, liver metastases are derived from a colorectal or neuroendocrine primary tumor. Liver resection with curative intent is standard for resectable cases, but unfortunately most patients are not initially resectable because of the size, location, and/or extent of disease; inadequate remnant liver volume; or comorbidities. For patients with liver-limited or liver-dominant colorectal liver metastases (CRLM), the current challenges are to use different locoregional treatments to convert some borderline unresectable cases to resectable, and improve local control and overall survival. Although neuroendocrine liver metastases (NELM) may behave in a relatively indolent manner from an oncologic perspective, significant morbidity may be caused by excess hormone production when compared with metastatic liver disease from other primaries, and liver-directed treatment may be beneficial in reducing symptoms and perhaps extending survival. In the multidisciplinary management of patients with liver metastases, local therapies are especially important. Local approaches may be complementary (ie, portal vein embolization) or an alternative (ie, ablation, hepatic arterial infusion, selective radioembolization, and stereotactic body radiotherapy) to surgical resection. This article evaluates the available evidence on current regional strategies for managing patients with liver metastases, with an emphasis on CRLM and NELM, highlighting the clinical usefulness and limitations of each modality.

The impact of article length on the number of future citations: a bibliometric analysis of general medicine journals.

BACKGROUND: The number of citations received is considered an index of study quality and impact. We aimed to examine the factors associated with the number of citations of published articles, focusing on the article length. METHODS: Original human studies published in the first trimester of 2006 in 5 major General Medicine journals were analyzed with regard to the number of authors and of author-affiliated institutions, title and abstract word count, article length (number of print pages), number of bibliographic references, study design, and 2006 journal impact factor (JIF). A multiple linear regression model was employed to identify the variables independently associated with the number of article citations received through January 2012. RESULTS: On univariate analysis the JIF, number of authors, article length, study design (interventional/observational and prospective/retrospective), title and abstract word count, number of author-affiliated institutions, and number of references were all associated with the number of citations received. On multivariate analysis with the logarithm of citations as the dependent variable, only article length [regression coefficient: 14.64 (95% confidence intervals: (5.76-23.50)] and JIF [3.37 (1.80-4.948)] independently predicted the number of citations. The variance of citations explained by these parameters was 51.2%. CONCLUSION: In a sample of articles published in major General Medicine journals, in addition to journal impact factors, article length and number of authors independently predicted the number of citations. This may reflect a higher complexity level and quality of longer and multi-authored studies.

Understanding of statistical terms routinely used in meta-analyses: an international survey among researchers.

OBJECTIVE: Biomedical literature is increasingly enriched with literature reviews and meta-analyses. We sought to assess the understanding of statistical terms routinely used in such studies, among researchers. METHODS: An online survey posing 4 clinically-oriented multiple-choice questions was conducted in an international sample of randomly selected corresponding authors of articles indexed by PubMed. RESULTS: A total of 315 unique complete forms were analyzed (participation rate 39.4%), mostly from Europe (48%), North America (31%), and Asia/Pacific (17%). Only 10.5% of the participants answered correctly all 4 "interpretation" questions while 9.2% answered all questions incorrectly. Regarding each question, 51.1%, 71.4%, and 40.6% of the participants correctly interpreted statistical significance of a given odds ratio, risk ratio, and weighted mean difference with 95% confidence intervals respectively, while 43.5% correctly replied that no statistical model can adjust for clinical heterogeneity. Clinicians had more correct answers than non-clinicians (mean score ± standard deviation: 2.27±1.06 versus 1.83±1.14, p<0.001); among clinicians, there was a trend towards a higher score in medical specialists (2.37±1.07 versus 2.04±1.04, p = 0.06) and a lower score in clinical laboratory specialists (1.7±0.95 versus 2.3±1.06, p = 0.08). No association was observed between the respondents' region or questionnaire completion time and participants' score. CONCLUSION: A considerable proportion of researchers, randomly selected from a diverse international sample of biomedical scientists, misinterpreted statistical terms commonly reported in meta-analyses. Authors could be prompted to explicitly interpret their findings to prevent misunderstandings and readers are encouraged to keep up with basic biostatistics.

Survival of patients operated for colorectal liver metastases and concomitant extra-hepatic disease: external validation of a prognostic model.

BACKGROUND: The presence of extra-hepatic disease (EHD) is no longer an absolute contraindication to surgery in patients with colorectal liver metastases (CRLM). Recently, a novel prognostic model predicting overall survival in such patients was proposed using five risk factors (EHD other than isolated lung metastases, CEA ≥10 ng/ml, >5 liver metastases, right colon as the primary CRC location, and diagnosis of EHD concomitant to CRLM recurrence). A bi-institutional database was used to perform an external validation of this model. METHODS: Ninety-seven patients operated for CRLM and EHD between 1982 and 2011 in two institutions was analyzed. The proposed prognostic model was validated in this cohort using Cox proportional hazards models and the concordance index (c). RESULTS: Of the five proposed risk factors, only EHD other than isolated lung metastases was found to independently predict overall survival [Hazards Ratio (HR) = 2.10 (95% CI: 1.01-4.40)]. Although, the number of risk factors was marginally associated with overall survival in univariate analysis (P = 0.049), the performance of the proposed prognostic model was poor when applied to our cohort (c = 0.64). CONCLUSION: The examined prognostic model of survival in patients with CRLM and EHD had poor performance. Further research is warranted to delineate the subset of patients who will benefit from surgery.

Technology-assisted versus clamp-crush liver resection: a systematic review and meta-analysis.

OBJECTIVE: To review the published evidence on technology-assisted liver resection regarding operative time, intraoperative bleeding, mortality, hospital stay, postoperative bile leak, and other outcomes. METHOD: A systematic review of clinical studies comparing liver resection using vessel sealing systems (VSSs-LigaSure), Cavitron Ultrasonic Surgical Aspirator (CUSA), or radiofrequency dissecting sealer (RFDS) with the conventional clamp-crushing technique (CC) was performed. Data for each modality were synthesized and individually compared with CC with the methodology of meta-analysis. RESULT: In all, 8 randomized controlled trials (RCTs) and 7 nonrandomized studies evaluating 1539 patients were included. Compared with CC, the VSS group (3 RCTs and 3 nonrandomized studies) had significantly lower blood loss by a mean of 109 mL (weighted mean difference [WMD] = -109; 95% confidence interval [CI] = -192, -26; data on 494 patients), lower risk for postoperative bile leak by 63% (odds ratio [OR] = 0.37; CI = 0.17, 0.78; 559 patients), and shorter total hospital stay by 2 days (WMD = -2.04; CI = -3.08, -1; 340 patients); no difference was noted for liver parenchyma transection time and mortality. No difference was noted between CUSA (4 RCTs and 1 nonrandomized study) or RFDS (3 RCTs and 3 nonrandomized studies) versus CC for any of the studied outcomes. CONCLUSION: Of the 3 modalities used in liver resection (VSS, CUSA, and RFDS), only VSS appeared to offer significant benefit over standard CC. However, the generalization of our findings is limited by the scarcity and clinical heterogeneity of the published studies. Large, well-designed and implemented RCTs are warranted to further investigate the usefulness of novel modalities used in liver resection.

Urinary tract analgesics for the treatment of patients with acute cystitis: where is the clinical evidence?

Acute cystitis is one of the most common health-related problems in the female population. Over the last few decades, a number of drugs labeled as 'urinary tract analgesics' were released; these are available over the counter and are gaining widespread resonance among the North American population. The main representatives of this class of drugs are phenazopyridine and methenamine hippurate. Methenamine's efficacy and side effects have been well studied in a recent systematic review. On the other hand, in contrast to its widespread use, the published clinical evidence regarding phenazopyridine's effectiveness and safety is scarce. In addition, consumers (potentially patients) appear to ignore the limitations of this kind of treatment. In this article, concerns regarding the use of over-the-counter uroanalgesics, with a focus on the relevant clinical evidence, are discussed.

Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC≤1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

Epidemiology and antimicrobial sensitivities of 536 multi-drug-resistant gram-negative bacilli isolated from patients treated on surgical wards.

BACKGROUND: In this era of increasing antimicrobial resistance, infections caused by multi-drug-resistant (MDR) gram-negative bacilli (GNB) are becoming more common and pose a challenge to all clinicians, including surgeons. METHODS: We evaluated the epidemiology and antimicrobial sensitivities of GNB isolated from patients treated on surgical wards at the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. The MDR isolates were defined according to an international expert proposal supported by the U.S. Centers for Disease Control and Prevention and the European Centre for Disease Prevention and Control. RESULTS: A total of 1,153 GNB were isolated; 536 (46.5%) were MDR. The most common isolates were Escherichia coli (312 [27.8%]; MDR rate 50.2%), Pseudomonas aeruginosa (298 [25.8%]; MDR rate 39.6%), Acinetobacter baumannii (137 [11.9%]; MDR rate 83.9%), and Klebsiella pneumoniae (112 [9.7%]; MDR rate 44.6%). Most pathogens were isolated from patients hospitalized in the Departments of Surgical Oncology (32.3%), Orthopedic and Trauma Surgery (31.8%), General Surgery (18.1%), and Pediatric Surgery (15.5%). The clinical specimens comprised pus (45.1%), normally sterile fluids (22.5%), urine (16.8%), blood (6.3%), and other body fluids. Most effective in vitro against all MDR pathogens were colistin (83%), meropenem (57%), and imipenem-cilastatin (56%). The MDR P. aeruginosa was susceptible most often to colistin (94%) and aminoglycosides (tobramycin 56%, amikacin 55%), MDR A. baumannii only to colistin (94%), and MDR K. pneumoniae to meropenem (92%) and aminoglycosides (amikacin 76%, gentamicin 74%). CONCLUSION: In a region with a high prevalence of antibiotic resistance, almost one-half of GNB isolated from surgical patients were MDR. Surgeons may consider these developments to guide empiric antibiotic therapy for infections caused by gram-negative pathogens.