Cause-specific mortality adjudication in the UPLIFT® COPD trial: findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT?) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.     

Treatment of large posttraumatic tibial bone defects using the Ilizarov method: a subjective outcome assessment

Background

The treatment of large posttraumatic tibial bone defects using the Ilizarov method was shown to be successful in several studies. These studies, however, typically focus on the radiological and functional outcome using objective parameters only. The aim of the present study was therefore to assess the objective and subjective outcome of a consecutive series of patients with large posttraumatic tibial bone defects using the Ilizarov method. Additionally, it was our goal to assess the physical and mental stress for the patients and their relatives during the long treatment period and the general health status at final follow-up.

Methods

A consecutive series of 15 patients with posttraumatic tibial bone defects of >30 mm after sustaining open tibial fractures and failure of internal fixation was included. The objective outcome was assessed at final follow-up using Paley’s criteria. For the assessment of the subjective outcome, all patients were asked to evaluate their satisfaction with the function of the lower leg, the cosmetic appearance and overall outcome as well. The physical and mental stress of the treatment for the patients and the nearest relative of patients were assessed at the time of frame removal using a custom-made questionnaire. The SF-36 was used to evaluate the general health status at final follow-up.

Results

Solid bone union with stable soft tissue coverage and eradication of infection was achieved in all patients despite a high complication rate. The functional outcome at final follow-up was excellent or good in all patients. The patients’ satisfaction with the overall outcome and the function of the lower extremity was high as well. The fear of amputation and complications was the major subjective burden for both the patients and their relatives. The long external fixation time is another relevant issue.

Conclusion

The Ilizarov method is a safe option for the treatment of large posttraumatic tibial bone defects after failure of internal fixation despite the high complication rate. It is essential to comment this to the patients and their relatives prior to the application of the frame increase their compliance with the long and emotionally draining treatment. The Ilizarov method is worth the effort only in patients, who will presumably comply with this treatment option and all of its drawbacks.     

Defining Treatment and Outcomes of Hepaticojejunostomy Failure Following Pancreaticoduodenectomy

Background

The overall complication rate after pancreaticoduodenectomy (PD) approaches 50 %, with anastomotic failure being the most frequent cause of serious postoperative morbidity. Hepaticojejunostomy leaks (also called bile leaks) are the second most common type of leak, behind pancreaticojejunostomy leaks, yet have been the focus of only a single study as reported by Suzuki et al. (Hepatogastroenterology 50:254–257, 12).

Methods

We reviewed the recent experience with bile leaks at a single, high-volume pancreatic surgery center over a six-year time period.

Results

Bile leaks were identified in 16 out of 715 patients (2.2 %). Low preoperative albumin was associated with an increased risk. Bile leaks typically manifested within the first week after surgery as bilious drainage in a surgically placed drain. Associated warning signs included fever and leukocytosis. Patients with a bile leak frequently developed other complications, including a pancreatic fistula, wound infection, delayed gastric emptying, and sepsis. The impact on perioperative outcomes was comparable to patients with a pancreatic leak. A grading system is proposed based on the International Study Group on Pancreatic Fistula model. Grade A bile leaks were classified as those managed with prolonged drainage by operatively placed drains, grade B bile leaks with percutaneous abdominal drainage, and grade C bile leaks with insertion of a percutaneous transhepatic biliary drainage.

Conclusions

Hepaticojejunostomy leaks are rare after PD. The complication severity ranges from trivial to life threatening and is comparable overall to pancreaticojejunostomy leaks. Surgical intervention is rarely, if ever, required. With prompt and aggressive management, a full recovery can be expected.     

Does Resident Experience Affect Outcomes in Complex Abdominal Surgery? Pancreaticoduodenectomy as an Example

Objectives

Understanding the factors contributing to improved postoperative patient outcomes remains paramount. For complex abdominal operations such as pancreaticoduodenectomy (PD), the influence of provider and hospital volume on surgical outcomes has been described. The impact of resident experience is less well understood.

Methods

We reviewed perioperative outcomes after PD at a single high-volume center between 2006 and 2012. Resident participation and outcomes were collected in a prospectively maintained database. Resident experience was defined as postgraduate year (PGY) and number of PDs performed.

Results

Forty-three residents and four attending surgeons completed 686 PDs. The overall complication rate was 44 %; PD-specific complications (defined as pancreatic fistula, delayed gastric emptying, intraabdominal abscess, wound infection, and bile leak) occurred in 28 % of patients. The overall complication rates were similar when comparing PGY 4 to PGY 5 residents (55.3 vs. 43.0 %; p?>?0.05). On univariate analysis, there was a difference in PD-specific complications seen between a PGY 4 as compared to a PGY 5 resident (44 vs. 27 %, respectively; p?=?0.016). However, this was not statistically significant when adjusted for attending surgeon. Logistic regression demonstrated that as residents perform more cases, PD-specific complications decrease (OR?=?0.97; p?<?0.01). For a resident's first PD case, the predicted probability of a PD-specific complication is 27 %; this rate decreases to 19 % by resident case number 15.

Conclusions

Complex cases, such as PD, provide unparalleled learning opportunities and remain an important component of surgical training. We highlight the impact of resident involvement in complex abdominal operations, demonstrating for the first time that as residents build experience with PD, patient outcomes improve. This is consistent with volume–outcome relationships for attending physicians and high-volume hospitals. Maximizing resident repetitive exposure to complex procedures benefits both the patient and the trainee.     

Defining a minimum number of examined lymph nodes improves the prognostic value of lymphadenectomy in pancreas ductal adenocarcinoma

BackgroundLymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy.MethodsData from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines.ResultsAs ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage.ConclusionThis is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients.