Relative Contributions of Complications and Failure to Rescue on Mortality in Older Patients Undergoing Pancreatectomy.

BACKGROUND: For pancreatectomy patients, mortality increases with increasing age. Our study evaluated the relative contribution of overall postoperative complications and failure to rescue rates on the observed increased mortality in older patients undergoing pancreatic resection at specialized centers. METHODS: We identified 2694 patients who underwent pancreatic resection from the American College of Surgeons' National Surgical Quality Improvement Pancreatectomy Demonstration Project at 37 high-volume centers. Overall morbidity and in-hospital mortality were determined in patients younger than 80 years (N = 2496) and 80 years or older (N = 198). Failure to rescue was the number of deaths in patients with complications divided by the total number of patients with postoperative complications. RESULTS: No significant differences were observed between patients younger than 80 years and those 80 years or older in the rates of overall complications (41.4% vs 39.4%, P = 0.58). In-hospital mortality increased in patients 80 years or older compared to patients younger than 80 years (3.0% vs 1.1%, P = 0.02). Failures to rescue rates were higher in patients 80 years or older (7.7% vs 2.7%, P = 0.01). Across 37 high-volume centers, unadjusted complication rates ranged from 25.0% to 72.2% and failure to rescue rates ranged from 0.0% to 25.0%. Among patients with postoperative complications, comorbidities associated with failure to rescue were ascites, chronic obstructive pulmonary disease, and diabetes. Complications associated with failure to rescue included acute renal failure, septic shock, and postoperative pulmonary complications. CONCLUSIONS: In experienced hands, the rates of complications after pancreatectomy in patients 80 years or older compared to patients younger than 80 years were similar. However, when complications occurred, older patients were more likely to die. Interventions to identify and aggressively treat complications are necessary to decrease mortality in vulnerable older patients.

Laparoscopy decreases complications for obese patients undergoing elective rectal surgery.

INTRODUCTION: While there are many reported advantages to laparoscopic surgery compared to open surgery, the impact of a laparoscopic approach on postoperative morbidity in obese patients undergoing rectal surgery has not been studied. Our goal was to determine whether obese patients undergoing laparoscopic rectal surgery experienced the same benefits as non-obese patients. METHODS: We identified patients undergoing rectal resections using the National Surgical Quality Improvement Project Participant Use Data File. We performed multivariable analyses to determine the independent association between laparoscopy and postoperative complications. RESULTS: A total of 26,437 patients underwent rectal resection. The mean age was 58.5 years, 32.6 % were obese, and 47.2 % had cancer. Laparoscopic procedures were slightly less common in obese patients compared to non-obese patients (36.0 vs. 38.2 %, p = 0.0006). In unadjusted analyses, complications were lower with the laparoscopic approach in both obese (18.9 vs. 32.4 %, p < 0.0001) and non-obese (15.6 vs. 25.3 %, p < 0.0001) patients. In a multivariable analysis controlling for potential confounders, the risk of postoperative complications increased as the degree of obesity worsened. The likelihood of experiencing a postoperative complication increased by 25, 45, and 75 % for obese class I, obese class II, and obese class III patients, respectively. A laparoscopic approach was associated with a 40 % decreased odds of a postoperative complication for all patients (OR 0.60, 95 % CI 0.56-0.64). CONCLUSION: Laparoscopic rectal surgery is associated with fewer complications when compared to open rectal surgery in both obese and non-obese patients. Obesity was an independent risk factor for postoperative complications. In appropriately selected patients, rectal surgery outcomes may be improved with a minimally invasive approach.

PREOP-Gallstones: A Prognostic Nomogram for the Management of Symptomatic Cholelithiasis in Older Patients.

OBJECTIVE AND BACKGROUND: The decision regarding elective cholecystectomy in older patients with symptomatic cholelithiasis is complicated. We developed and validated a prognostic nomogram to guide shared decision making for these patients. METHODS: We used Medicare claims (1996-2005) to identify the first episode of symptomatic cholelithiasis in patients older than 65 years who did not undergo hospitalization or elective cholecystectomy within 2.5 months of the episode. We described current patterns of care and modeled their risk of emergent gallstone-related hospitalization or cholecystectomy at 2 years. Model discrimination and calibration were assessed using a random split sample of patients. RESULTS: We identified 92,436 patients who presented to the emergency department (8.3%) or physician's office (91.7%) and who were not immediately admitted. The diagnosis for the initial episode was biliary colic/dyskinesia (65.3%), acute cholecystitis (26.6%), choledocholithiasis (5.7%), or gallstone pancreatitis (2.4%). The 2-year emergent gallstone-related hospitalization rate was 11.1%, with associated in-hospital morbidity and mortality rates of 56.5% and 6.5%. Factors associated with gallstone-related acute hospitalization included male sex, increased age, fewer comorbid conditions, complicated biliary disease on initial presentation, and initial presentation to the emergency department. Our model was well calibrated and identified 51% of patients with a risk less than 10% for 2-year complications and 5.4% with a risk more than 40% (C statistic, 0.69; 95% confidence interval, 0.63-0.75). CONCLUSIONS: Surgeons can use this prognostic nomogram to accurately provide patients with their 2-year risk of developing gallstone-related complications, allowing patients and physicians to make informed decisions in the context of their symptom severity and its impact on their quality of life.

Surgeon and Facility Variation in the Use of Minimally Invasive Breast Biopsy in Texas.

OBJECTIVE AND BACKGROUND: Minimally invasive breast biopsy (MIBB) rates remain well below guideline recommendations of more than 90% and vary across geographic areas. Our aim was to determine the variation in use attributable to the surgeon and facility and determine the patient, surgeon, and facility characteristics associated with the use of MIBB. METHODS: We used 100% Texas Medicare claims data (2000-2008) to identify women older than 66 years with a breast biopsy (open or minimally invasive) and subsequent breast cancer diagnosis/operation within 1 year. The percentage of patients undergoing MIBB as the first diagnostic modality was estimated for each surgeon and facility. Three-level hierarchical generalized linear models (patients clustered within surgeons within facilities) were used to evaluate variation in MIBB use. RESULTS: A total of 22,711 patients underwent a breast cancer operation by 1226 surgeons at 525 facilities. MIBB was the initial diagnostic modality in 62.4% of cases. Only 7.0% of facilities and 12.9% of surgeons used MIBB for more than 90% of patients. In 3-level models adjusted for patient characteristics, the percentage of patients who received MIBB ranged from 7.5% to 96.0% across facilities (mean = 50.1%, median = 49.2%) and from 8.0% to 87.0% across surgeons (mean = 50.3%, median = 50.9%). The variance in MIBB use was attributable to facility (8.8%) and surgeon (15.4%) characteristics. Lower surgeon and facility volume, longer surgeon years in practice, and smaller facility bed size were associated with lower rates of MIBB use. CONCLUSIONS: Identification of surgeon and facility characteristics associated with low use of MIBB provides potential targets for interventions to improve MIBB rates and decrease variation in use. TYPE OF STUDY: Retrospective cohort.

Impact of liver-directed therapy in colorectal cancer liver metastases.

BACKGROUND: There is a paucity of data on the current management and outcomes of liver-directed therapy (LDT) in older patients presenting with stage IV colorectal cancer (CRC). The aim of the study was to evaluate treatment patterns and outcomes in use of LDT in the setting of improved chemotherapy. METHODS: We used Cancer Registry and linked Medicare claims to identify patients aged ≥66 y undergoing surgical resection of the primary tumor and chemotherapy after presenting with stage IV CRC (2001-2007). LDT was defined as liver resection and/or ablation-embolization. RESULTS: We identified 5500 patients. LDT was used in 34.9% of patients; liver resection was performed in 1686 patients (30.7%), and ablation-embolization in 554 patients (10.1%), with 322 patients having both resection and ablation-embolization. Use of LDT was negatively associated with increasing year of diagnosis (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.93-0.99), age >85 y (OR = 0.61, 95% CI 0.45-0.82), and poor tumor differentiation (OR = 0.73, 95% CI 0.64-0.83). LDT was associated with improved survival (median 28.4 versus 21.1 mo, P < 0.0001); however, survival improved for all patients over time. We found a significant interaction between LDT and period of diagnosis and noted a greater survival improvement with LDT for those diagnosed in the late (2005-2007) period. CONCLUSIONS: Older patients with stage IV CRC are experiencing improved survival over time, independent of age, comorbidity, and use of LDT. However, many older patients deemed to be appropriate candidates for resection of the primary tumor and receipt of systemic chemotherapy did not receive LDT. Our data suggest that improved patient selection may be positively impacting outcomes. Early referral and optimal selection of patients for LDT has the potential to further improve survival in older patients presenting with advanced colorectal cancer.

Evaluating comparative effectiveness with observational data: endoscopic ultrasound and survival in pancreatic cancer.

BACKGROUND: A previous observational study reported that endoscopic ultrasound (EUS) is associated with improved survival in older patients with pancreatic cancer. The objective of this study was to reevaluate this association using different statistical methods to control for confounding and selection bias. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data (1992-2007) was used to identify patients with locoregional pancreatic cancer. Two-year survival in patients who did and did not receive EUS was compared by using standard Cox proportional hazards models, propensity score methodology, and instrumental variable analysis. RESULTS: EUS was associated with improved survival in both unadjusted (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.63-0.72) and standard regression analyses (HR = 0.78, 95% CI = 0.73-0.84) which controlled for age, sex, race, marital status, tumor stage, SEER region, Charlson comorbidity, year of diagnosis, education, preoperative biliary stenting, chemotherapy, radiation, and pancreatic resection. Propensity score adjustment, matching, and stratification did not attenuate this survival benefit. In an instrumental variable analysis, the survival benefit was no longer observed (HR = 1.00, 95% CI = 0.73-1.36). CONCLUSIONS: These results demonstrate the need to exercise caution in using administrative data to infer causal mortality benefits with diagnostic and/or treatment interventions in cancer research.

Factors associated with delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: The factors associated with delayed gastric emptying (DGE) after a pancreaticoduodenectomy (PD) are not definitively known. METHODS: From November 2011 through to May 2012, data were prospectively collected on 711 patients undergoing a pancreaticoduodenectomy or total pancreatectomy as part of the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project. Bivariate and multivariate models were employed to determine the factors that predicted DGE. RESULTS: In the 711 patients, the overall rate of DGE was 20.1%. In a bivariate analysis, intra-operative factors such as pylorus-preservation (47.1% versus 43.7%, P = 0.40), intra-operative drain placement (85.5%, versus 85.1%, P = 0.91) and an antecolic compared with a retrocolic gastrojejunostomy (60.1% versus 65.1%, P = 0.26) were not different between the DGE and no DGE groups. Pancreatic fistula formation (31.2% versus 10.1%), post-operative sepsis (21.7% versus 7.0%), organ space surgical site infection (SSI) (23.9% versus 7.9%), need for percutaneous drainage (23.0% versus 10.6%) and reoperation (10.6% versus 3.1%) were higher in patients with DGE (P < 0.0001). In a multivariable model, only pancreatic fistula, post-operative sepsis and reoperation were independently associated with DGE. DISCUSSION: In this multicentre study, only post-operative complications were associated with DGE. Neither pylorus preservation nor route of enteric reconstruction (antecolic versus retrocolic) was associated with delayed gastric emptying.

Actin is part of pre-initiation complexes and is necessary for transcription by RNA polymerase II.

Actin is abundant in the nucleus and has been implicated in transcription; however, the nature of this involvement has not been established. Here we demonstrate that beta-actin is critically involved in transcription because antibodies directed against beta-actin, but not muscle actin, inhibited transcription in vivo and in vitro. Chromatin immunoprecipitation assays demonstrated the recruitment of actin to the promoter region of the interferon-gamma-inducible MHC2TA gene as well as the interferon-alpha-inducible G1P3 gene. Further investigation revealed that actin and RNA polymerase II co-localize in vivo and also co-purify. We employed an in vitro system with purified nuclear components to demonstrate that antibodies to beta-actin block the initiation of transcription. This assay also demonstrates that beta-actin stimulates transcription by RNA polymerase II. Finally, DNA-binding experiments established the presence of beta-actin in pre-initiation complexes and also showed that the depletion of actin prevented the formation of pre-initiation complexes. Together, these data suggest a fundamental role for actin in the initiation of transcription by RNA polymerase II.

Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma.

INTRODUCTION: Multimodality therapy with chemotherapy and operative resection is recommended for patients with locoregional pancreatic cancer but is not received by many patients. OBJECTIVE: To evaluate patterns in the use and timing of chemotherapy and resection and factors associated with receipt of multimodality therapy in older patients with locoregional pancreatic cancer. METHODS: We used Surveillance, Epidemiology, and End Results-linked Medicare data (1992-2007) to identify patients with locoregional pancreatic adenocarcinoma. Multimodality therapy was defined as receipt of both chemotherapy and pancreatic resection. Logistic regression was used to determine factors independently associated with receipt of multimodality therapy. Log-rank tests were used to identify differences in survival for patients stratified by type and timing of treatment. RESULTS: We identified 10,505 patients with pancreatic adenocarcinoma. 5,358 patients (51.0%) received either chemotherapy or surgery, with 1,166 patients (11.1%) receiving both modalities. Resection alone was performed in 1,138 patients (10.8%), and chemotherapy alone was given to 3,054 (29.1%) patients. In patients undergoing resection as the initial treatment modality, 49.4% never received chemotherapy; 97.4% of patients who underwent chemotherapy as the initial treatment modality never underwent resection. The use of multimodality therapy increased from 7.4% of patients in 1992-1995 to 13.8% of patients in 2004-2007 (P < .0001). The 2-year survival was 41.0% for patients receiving multimodality therapy, 25.1% with resection alone, and 12.5% with chemotherapy alone (P < .0001). Of the patients receiving multimodality therapy, chemotherapy was delivered in the adjuvant setting in 93.1% and in the neoadjuvant setting in 6.9%, with similar 2-year survival with either approach (neoadjuvant vs adjuvant, 46.9% vs 40.6%; P = .16). Year of diagnosis, white race, less comorbidity, and no vascular invasion were independently associated with receipt of multimodality therapy. CONCLUSION: Only half of older patients with locoregional pancreatic cancer receive any treatment, and fewer than one quarter of treated patients receive multimodality therapy. Nearly all patients receiving chemotherapy as the initial treatment modality did not undergo resection, whereas half of those undergoing resection first received chemotherapy. When multimodality therapy is used, the vast majority of patients had chemotherapy in the adjuvant setting with a similar survival, regardless of approach.

Trends in treatment and survival in older patients presenting with stage IV colorectal cancer.

INTRODUCTION: Trends in the use of modern chemotherapeutic regimens, primary tumor resection, and the timing of chemotherapy and resection in older patients with stage IV colorectal cancer have not been evaluated. METHODS: We used Cancer Registry- and Medicare-linked data (2000-2009) to describe time trends in resection of the primary tumor and receipt of chemotherapy in patients ≥ 66 presenting with stage IV colorectal cancer (N = 16,168). RESULTS: The mean age was 77.8 ± 7.3 years; 53.8 % were women and 82.9 % were white. Primary cancer sites were colon in 83.4 % and rectum in 16.6 %. Resection of the primary tumor decreased from 64.6 to 57.1 % (P < 0.0001) from 2001 to 2009. Systemic chemotherapy was given to 45.1 % of the patients. While the use of chemotherapy was stable over time (P = 0.48), the use of modern regimens containing oxaliplatin or irinotecan increased from 40.9 to 75.4 % (P < 0.0001). Bevacizumab use increased from 0.10 to 54.2 % (P < 0.0001). Survival improved by 4 % per year even after controlling for treatment and tumor location (HR = 0.96, 95 % CI 0.95-0.97). CONCLUSIONS: Survival in older patients with stage IV disease is improving over time. Surgical resection is still performed in the majority of patients. Resection rates decreased while modern chemotherapy was rapidly adopted perhaps suggesting a shift in practice patterns.

Cost-effectiveness of elective laparoscopic cholecystectomy versus observation in older patients presenting with mild biliary disease.

Our objective was to determine the probability threshold for recurrent symptoms at which elective cholecystectomy compared to observation in older patients with symptomatic cholelithiasis is the more effective and cost-effective option. We built a decision model of elective cholecystectomy versus observation in patients >65 presenting with initial episodes of symptomatic cholelithiasis that did not require initial hospitalization or cholecystectomy. Probabilities for subsequent hospitalization, emergency cholecystectomy, and perioperative complications were based on previously published probabilities from a 5 % national sample of Medicare patients. Costs were estimated from Medicare reimbursements and from the Healthcare Cost and Utilization Project. Utilities (quality-adjusted life years, QALYs) were obtained from established literature estimates. Elective cholecystectomy compared to observation in all patients was associated with lower effectiveness (-0.10 QALYs) and had an increased cost of $3,422.83 per patient at 2-year follow-up. Elective cholecystectomy became the more effective option when the likelihood for continued symptoms exceeded 45.3 %. Elective cholecystectomy was both more effective and less costly when the probability for continued symptoms exceeded 82.7 %. An individualized shared decision-making strategy based on these data can increase elective cholecystectomy rates in patients at high risk for recurrent symptoms and minimize unnecessary cholecystectomy for patients unlikely to benefit.

Quality of post-treatment surveillance of early stage breast cancer in Texas.

BACKGROUND: Only annual mammography and physical examination are recommended for the post-treatment surveillance of early stage breast cancer. METHODS: We used Texas Cancer Registry-Medicare linked data (2001-2007) to identify physician visits and use of mammography, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) CT in patients ≥ 66 years old with ductal carcinoma in situ and stage I-III ductal carcinoma who underwent curative-intent operations. We also evaluated the trends in use of recommended and nonrecommended tests. RESULTS: We identified 8,598 patients with resected ductal carcinoma in situ (37.3%) or invasive ductal cancer (62.7%). Breast-conserving therapy was performed in 59%. Only 55% saw a physician twice a year for 2 years and underwent annual mammography for 2 consecutive years in the surveillance period. Mammography use decreased from 81% in 2001 to 75% in 2007 (P < .0001), and breast MRI use rose from 0.5% to 7.0% (P < .0001). For asymptomatic patients, the use of CT/MRI of the abdomen, chest, and head was 27%, 23%, and 22%, and this slightly increased during the study period. There was a significant increase in PET/PET CT use, from 2% in 2001 to 9% in 2007 (P < .0001). There was a concomitant decrease in bone scan use from 21% in 2001 to 13% in 2007 (P < .0001). CONCLUSION: Adherence to evidence-based guidelines has been substandard and the use of nonrecommended tests has persisted over the study period. The rise in PET use and attendant decrease in bone scan implicates a population receiving PET scan in lieu of bone scan for surveillance of asymptomatic metastatic disease. In an elderly population of breast cancer patients in Texas, these findings imply both underuse and overuse.

Physician follow-up and observation of guidelines in the post treatment surveillance of colorectal cancer.

BACKGROUND: Guidelines for post resection surveillance of colorectal cancer recommend a collection of the patient's history and physical examination, testing for carcinoembryonic antigen (CEA), and colonoscopy. No consistent guidelines exist for the use of abdominal computed tomography (CT) and position emission tomography (PET)/PET-CT. The goal of our study was to describe current trends, the impact of oncologic follow-up on guideline adherence, and the patterns of use of nonrecommended tests. METHODS: We used Texas Cancer Registry-Medicare-linked data (2000-2009) to identify physician visits, CEA testing, colonoscopy, abdominal CT, and PET/PET-CT scans in patients ≥ 66 years old with stage I-III colorectal cancer who underwent curative resection. Compliance with guidelines was assessed with a composite measure of physician visits, CEA tests, and colonoscopy use from start of surveillance. RESULTS: In patients who survived 3 years, the overall compliance with guidelines was 25.1%. In patients seen regularly by a medical oncologist, compliance with guidelines increased to 61.5% compared with 8.8% for those not seen by a medical oncologist regularly (P < .0001). The use of abdominal CT and PET/PET-CT increased from 57.5% and 9.5%, respectively, in 2001 to 65.8% and 24.6% (P < .0001) in 2006. Patients who saw a medical oncologist were more likely to get cross-sectional imaging than those who did not (P < .0001). CONCLUSION: Compliance with current minimum guidelines for post treatment surveillance of colorectal cancer is low and the use of nonrecommended testing has increased over time. Both compliance and use of nonrecommended tests are markedly increased in patients seen by a medical oncologist. The comparative effectiveness of CT and PET/PET-CT in the surveillance of colorectal cancer patients needs further examination.

Nuclear myosin I is necessary for the formation of the first phosphodiester bond during transcription initiation by RNA polymerase II.

The nuclear isoform of myosin, Nuclear Myosin I (NMI) is involved in transcription by RNA polymerase I. Previous experiments showing that antibodies to NMI inhibit transcription by RNA polymerase II using HeLa cell nuclear extract (NE) suggested that NMI might be a general transcription factor for RNA polymerases. In this study we used a minimal in vitro transcription system to investigate the involvement of NMI in transcription by RNA polymerase II in detail. We demonstrate that NMI co-purifies with RNA polymerase II and that NMI is necessary for basal transcription by RNA polymerase II because antibodies to NMI inhibit transcription while adding NMI stimulates transcription. Further investigation revealed that NMI is specifically involved in transcription initiation. Finally, by employing an abortive transcription initiation assay, we demonstrate that NMI is crucial for the formation of the first phosphodiester bond during transcription initiation.