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Objective: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. Background: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. Methods: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology--pro-inflammatory activity [nuclear factor-κB (NF-kB), activator protein 1 (AP-1)], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein (CREB)], and protective cellular responses [interferon-regulatory factor (IRF) and signal transducer and activator of transcription (STAT)]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. Results: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB, activator protein 1, down-regulated IRF, and signal transducer and activator of transcription) and SNS activation (up-regulated CREB). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF. These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. Conclusions: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. Background: Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown. Methods: Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2−), ER+/HER2+, and ER−/HER2+ disease. Results: Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001–1.126, P =0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151–0.781, P =0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: −0.987–1.116, P =0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ2=42004914 (p =3.70×10−5) in patients with TNBC. Conclusions: In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC. [ABSTRACT FROM AUTHOR]

Objective: To assess contemporary trends in the National Institutes of Health (NIH) Career Development (K) Awards within the Departments of Surgery and its impact on the likelihood of achieving independent R01 grants. Background: The NIH provides K-type Career Development Awards to nurture young clinicians toward a productive academic career, thereby maintaining a pipeline of physician-scientists. However, the impact of K awards on career trajectory of surgeons remains unclear. Methods: The NIH grant data was queried for all new K08/K23 grants awarded to Departments of Surgery (1999–2019). Principal Investigators’ data and grant-related information was obtained. Results: The NIH awarded 298 K08/23 surgical grants ($41,893,170) over the last 2 decades. Median budget increased from $116,370 to $167,508 (P<0.001). Of grantees, 83.2% were MDs, 15.1% MD/PhD, and 1.7% PhDs, with 25.2% being women. Principal Investigators’ were mostly practicing surgeons (91.1%) with fellowship training (82.4%) and young in their careers {4 [interquartile ranges (IQR) 4] years of experience}. Vascular surgery (15.9%), Complex General Surgical Oncology (15.1%), and Trauma/Critical Care (14.6%) were the most frequent specialties. Awards were associated with 3,336 publications [median 8/project (IQR 13)]. The majority of K grantees (77.2%) currently hold an academic faculty position. Only 32.2% of awardees received independent R01 grant funding, at a median of 5.5 years (IQR 5) after their K awards. Sex (P = 0.71), previous fellowship training (P = 0.63), type of surgical specialty (P = 0.72), or MD/PhD degree (P = 0.75) were not associated with increased likelihood of achieving a subsequent R01 award. Conclusion: Although the majority of K awardees maintain an academic career, only a limited number of grantees progress to obtain NIH R01 funding. Increased mentorship, financial support, and infrastructure are needed to facilitate career development awardees opportunities to enhance their ability to achieve independent funding. [ABSTRACT FROM AUTHOR]

Objective: We present a holistic perioperative optimization approach led by a CI team with the goal to optimize the workflow within our EHR, improve operative room metrics and user satisfaction. Summary of Background Data: The EHR has become integral to perioperative care. Many approaches are utilized to improve performance including systems-based approaches, process redesign, lean methodology, checklists, root cause analysis, and parallel processing. Although most reports describe strategies improving day or surgery productivity, few include perioperative interventions to improve efficiencies. Methods: An interdisciplinary CI team consisting of clinicians, informatics specialists, and analysts spent 6 weeks assessing users and optimizing all perioperative areas (scheduling, day of surgery, postop discharge/admission). Elbow-to-elbow retraining and simultaneous content development was performed utilizing an Agile workflow process optimization with the Scrum framework. This iterative approach averaged 1 week from build to change implementation. Pre/post optimization surveys were sent. Results: Two hundred forty-two perioperative enhancements were completed. While most impacted documentation, all areas were enhanced including billing, reporting, registration, device integration, scheduling, central supply, and so on. FCOTS improved from <70% to >85% and total delay was halved. These parameters were consistently sustained for over 1 year after the 6-week optimization. While only 5% of pre-optimization users agreed to proficiency in the EHR system, this improved to 70% post-optimization. Furthermore, EHR confidence and acceptance improved from 40% to 90%. Conclusions: To improve workflow efficiency, all who contribute to the perioperative process must be assessed. This IT driven initiative resulted in improved FCOTS, perioperative workflows, and user satisfaction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the contemporary trends in National Institutes of Health (NIH) grants awarded to surgical investigators, including potential disparities. Background: The NIH remains the primary public funding source for surgical research in the United States; however, the patterns for grants and grantees are poorly understood. Methods: NIH RePORTER was queried for new grants (R01, -03, -21) awarded to Departments of Surgery (DoS). Principal investigators' (PIs) data were extracted from publicly available information from their institutions' websites and/or professional social media accounts. Results: The NIH awarded 1101 new grants (total: $389,006,782; median: $313,030) between 2008 and 2018. Funding to DoS has doubled in the last 10 years ($22,983,500-2008 to $49,446,076-2018). Midwest/Southeast institutions and surgical oncologists accounted for majority of the grants (31.9% and 24.5%, respectively). Only 24.7% of the projects were led by female PIs, who were predominantly nonphysician PhD scientists (52% vs 37.7% PhD-only male PIs; P = 0.002). During this time, there was a significant increase from 12.4% to 31.7% in grants awarded to PIs with >15 years of experience. These grants were associated with 8215 publications; however, only 13.2% were published in high-impact journals (impact factor -10). 4.4% of the grants resulted in patents, and these were associated with higher award amounts ($345,801 vs $311,350; P = 0.030). On multivariate analysis, combined MD/PhD degree [odds ratio (OR) 5.98; 95% confidence interval (CI) 2.18-16.39; P < 0.001] was associated with improved odds of patent creation; conversely, practicing surgeon PIs affected patent creation negatively (OR 0.31; 95% CI 0.11-0.85; P = 0.024). Conclusion: In the last decade, a greater proportion of NIH grants in DoS were awarded to more experienced investigators. Disparities exist among grantees, and female investigators are underrepresented, especially among practicing surgeons. [ABSTRACT FROM AUTHOR]

Objective: To perform a comprehensive assessment of long-term quality of life (QOL) and gastrointestinal (GI) function in patients following pancreaticoduodenectomy (PD). Summary of Background Data: Survival after PD has greatly improved and thus has resulted in a larger population of survivors, yet long-term QOL and GI function after PD is largely unknown. Methods: Patients were identified from a global online support group. QOL was measured using the Short Form-36, while GI function was assessed using the Gastrointestinal Symptom Rating Scale. QOL and GI function were analyzed across subgroups based on time after PD. QOL was compared with preoperative measurements and with established values of a general healthy population (GHP). Multivariate linear regression was used to identify predictors of QOL. Results: Of the 7605members of the online support group, 1102 responded to the questionnaire with 927 responders meeting inclusion criteria. Seven hundred seventeen (77.3%) of these responders underwent PD for malignancy. Mean age was 57 ± 12 years and 327 (35%) were male. At the time of survey, patients were 2.0 (0.7, 4.3) years out from surgery, with a maximum 30.7-year response following PD. Emotional and physical domains of QOL improved with time and surpassed preoperative levels between 6 months and 1 year after PD (both P<0.001). Each GI symptom worsened over time (all P < 0.001). Independent predictors of general QOL in long-term survivors (> 5 years) included total GSRS score [β = -1.70 (-1.91, -1.50)], female sex [β = 3.58 (0.67, 6.46)], and being a cancer survivor [b = 3.93 (0.60, 7.25)]. Conclusions: Long-term QOL following PD improves over time, however never approaches that of a GHP. GI dysfunction persists in long-term survivors and is an independent predictor of poor QOL. Long-term physical, psychosocial, and GI functional support after PD is encouraged. [ABSTRACT FROM AUTHOR]

There is an unacceptably high burden of death and disability from conditions that are treatable by surgery, worldwide and especially in low- and middle-income countries (LMICs). The major actions to improve this situation need to be taken by the surgical communities, institutions, and governments of the LMICs. The US surgical community, including the US academic surgical community, has, however, important roles to play in addressing this problem. The American Surgical Association convened a Working Group to address how US academic surgery can most effectively decrease the burden from surgically treatable conditions in LMICs. The Working Group believes that the task will be most successful (1) if the epidemiologic pattern in a given country is taken into account by focusing on those surgically treatable conditions with the highest burdens; (2) if emphasis is placed on those surgical services that are most cost-effective and most feasible to scale up; and (3) if efforts are harmonized with local priorities and with existing global initiatives, such as the World Health Assembly with its 2015 resolution on essential surgery. This consensus statement gives recommendations on how to achieve those goals through the tools of academic surgery: clinical care, training and capacity building, research, and advocacy. Through all of these, the ethical principles of maximally and transparently engaging with and deferring to the interests and needs of local surgeons and their patients are of paramount importance. Notable benefits accrue to US surgeons, trainees, and institutions that engage in global surgical activities. [ABSTRACT FROM AUTHOR]

Objective: The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations. Methods: Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia. Results: Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery. Conclusion: Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes., Background: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS., Methods: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively., Results: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS., Conclusions: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort., Competing Interests: N.G. is funded by an Breast Cancer Research Foundation, Paul Calabresi Award, American Surgical Association Fellowship Award, American Society of Clinical Oncology (ASCO) Career Development Award, and an NIH P50 Transdisciplinary Cancer Control Support Grant. Also, she is a paid technical consultant for the World Health Organization. M.A. is funded by the Florida Breast Cancer Foundation; NIH grants R01CA206456, UG3 CA260317, R61 CA263335, R37 CA255875; a PCORI grant AD-2020C3-21171; and an NIH P50 Transdisciplinary Cancer Control Support Grant. Also, he is a paid consultant for Blue Note Therapeutics and Atlantis Healthcare. He is also the inventor of Cognitive Behavioral Stress Management, filed with the University of Miami as UMIP-483, which is licensed to Blue Note Therapeutics. S.C. is funded by the NIH K12 and NIA P30-AG017265. A.E.H. is funded by the Ruth L. Kirschstein Institutional National Research Service Award, T32CA211034. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess contemporary trends in the National Institutes of Health (NIH) Career Development (K) Awards within the Departments of Surgery and its impact on the likelihood of achieving independent R01 grants., Background: The NIH provides K-type Career Development Awards to nurture young clinicians toward a productive academic career, thereby maintaining a pipeline of physician-scientists. However, the impact of K awards on career trajectory of surgeons remains unclear., Methods: The NIH grant data was queried for all new K08/K23 grants awarded to Departments of Surgery (1999-2019). Principal Investigators' data and grant-related information was obtained., Results: The NIH awarded 298 K08/23 surgical grants ($41,893,170) over the last 2 decades. Median budget increased from $116,370 to $167,508 (P<0.001). Of grantees, 83.2% were MDs, 15.1% MD/PhD, and 1.7% PhDs, with 25.2% being women. Principal Investigators' were mostly practicing surgeons (91.1%) with fellowship training (82.4%) and young in their careers {4 [interquartile ranges (IQR) 4] years of experience}. Vascular surgery (15.9%), Complex General Surgical Oncology (15.1%), and Trauma/Critical Care (14.6%) were the most frequent specialties. Awards were associated with 3,336 publications [median 8/project (IQR 13)]. The majority of K grantees (77.2%) currently hold an academic faculty position. Only 32.2% of awardees received independent R01 grant funding, at a median of 5.5 years (IQR 5) after their K awards. Sex (P = 0.71), previous fellowship training (P = 0.63), type of surgical specialty (P = 0.72), or MD/PhD degree (P = 0.75) were not associated with increased likelihood of achieving a subsequent R01 award., Conclusion: Although the majority of K awardees maintain an academic career, only a limited number of grantees progress to obtain NIH R01 funding. Increased mentorship, financial support, and infrastructure are needed to facilitate career development awardees opportunities to enhance their ability to achieve independent funding., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019)., Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking., Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology., Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety., Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Objective: To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy., Background: Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown., Methods: Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19-9 decrease ≥50% vs <50%) and pathological response (complete, pCR; partial, pPR or limited, pLR) following NAC., Results: Of 274 included patients, 46.4% were borderline resectable, 25.5% locally advanced, and 83.2% had pancreatic head/neck tumors. Vein resection was performed in 34.7% and 30-day mortality was 2.2%. R0 and pCR rates were 82.5% and 6%, respectively. Median, 3-year, and 5-year OS were 32 months, 46.3%, and 30.3%, respectively. OS, L-RFS, and MFS were superior in patients with marked biochemical response (CA 19-9 decrease ≥50% vs <50%; OS: 42.3 vs 24.3 months, P < 0.001; L-RFS-27.3 vs 14.1 months, P = 0.042; MFS-29.3 vs 13 months, P = 0.047) and pathological response [pCR vs pPR vs pLR: OS- not reached (NR) vs 40.3 vs 26.1 months, P < 0.001; L-RFS-NR vs 24.5 vs 21.4 months, P = 0.044; MFS-NR vs 23.7 vs 20.2 months, P = 0.017]. There was no difference in L-RFS, MFS, or OS between patients who received FLX or GNP., Conclusion: This large, multicenter study shows that improved biochemical, pathological, and clinical responses associated with NAC FLX or GNP result in improved OS, L-RFS, and MFS in PDAC. NAC with FLX or GNP has similar survival outcomes.

Introduction: During pancreaticoduodenectomy (PD) for ductal adenocarcinoma, a frozen section (FS) neck margin is typically assessed, and if positive, additional pancreas is removed to achieve an R0 margin. We analyzed the association of this practice with improved overall survival (OS)., Methods: Patients who underwent PD for pancreatic ductal adenocarcinoma from January 2000 to August 2012 at 8 academic centers were classified by neck margin status as negative (R0) or microscopically positive (R1) on the basis of FS and permanent section (PS). Impact on OS of converting an FS-R1-neck margin to a PS-R0-neck margin by additional resection was assessed., Results: A total of 1399 patients had FS neck margins analyzed. Median OS was 19.7 months. On FS, 152 patients (10.9%) were R1, and an additional 51 patients (3.6%) had false-negative FS-R0 margins. PS-R0-neck was achieved in 1196 patients (85.5%), 131 patients (9.3%) remained PS-R1, and 72 patients (5.1%) were converted from FS-R1-to-PS-R0 by additional resection. Median OS for PS-R0-neck patients was 21.1 months versus 13.7 months for PS-R1-neck patients (P < 0.001) and 11.9 months for FS-R1-to-PS-R0 patients (P < 0.001). Both FS-R1-to-PS-R0 and PS-R1-neck patients had larger tumors (P = 0.001), more perineural invasion (P = 0.02), and more node positivity (P = 0.08) than PS-R0-neck patients. On multivariate analysis controlling for adverse pathologic factors, FS-R1-to-PS-R0 conversion remained associated with significantly worse OS compared with PS-R0-neck patients (hazard ratio: 1.55; P = 0.009)., Conclusions: For patients who undergo pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, additional resection to achieve a negative neck margin after positive frozen section is not associated with improved OS.

Objective and Background: Morbidity, mortality, and length of hospital stay after pancreaticoduodenectomy (PD) have significantly decreased over recent decades. Despite this progress, early readmission rates after PD have been reported as high as 50%. Few reports have delineated factors associated with readmission after PD., Methods: The medical records of 6 high-volume institutions were reviewed for patients who underwent PD between 2005 and 2010. Data collection included patient characteristics, medical comorbidities, and perioperative factors. Analysis included readmissions up to 90 days after PD., Results: A total of 1302 patients underwent PD across all institutions. The 30-day and 90-day readmission rates were 15% and 19%, respectively. The most common reasons for 30-day readmission included infectious complications (n = 65) and delayed gastric emptying (n = 29). The most common reasons for readmission after 90 days included wound infections and intra-abdominal abscess (n = 75) and failure to thrive (n = 38). On multivariate analysis, factors associated with higher readmission rates included a preoperative diagnosis of chronic pancreatitis, higher transfusion requirements, and postoperative complications including intra-abdominal abscess and pancreatic fistula (all P < 0.02). Factors not associated with higher readmission rates included advanced age, body mass index, cardiovascular/pulmonary comorbidities, diabetes, steroid use, Whipple type (standard vs pylorus preserving PD), preoperative endobiliary stenting, and vascular reconstruction., Conclusions: These multi-institutional data represent a large experience of PD without the biases typically of single center studies. Factors related to infection, nutritional status, and delayed gastric emptying were the most common reasons for readmission after PD. Postoperative complications including pancreatic fistula predicted higher rates of readmission.

Objectives: Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer., Methods: Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls., Results: The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively., Conclusions: Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer.

Objectives: The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways play key and often complementary roles in the pathogenesis of colorectal cancer (CRC). This study explores the clinical and biological effects of combined blockade of these pathways., Methods: Cetuximab-naive patients with refractory CRC were treated with cetuximab (400 mg/m loading dose followed by weekly cetuximab at 250 mg/m) and celecoxib (200 mg orally twice daily). Urinary PGE-M, a stable metabolite of PGE2 that correlates with in vivo COX-2 activity, and serum TGF-α, a ligand that binds to EGFR, were measured serially to assess the biological effect of COX-2 and EGFR blockade., Results: Seventeen patients accrued in this study. Of the 13 patients evaluable for response, 2 (15.4%) had confirmed partial responses, 4 (30.8%) had stable disease, and 7 (53.8%) had progressive disease. The median progression-free survival for all evaluable patients was 55 days (95% confidence interval, 45-112; range, 10-295 d). This study was terminated early owing to lack of sufficient clinical activity. There were no statistically significant differences in serum TGF-α or urinary PGE-M between cycles in responders or nonresponders., Conclusions: This regimen resulted in response rates similar to those published for cetuximab monotherapy in patients with recurrent CRC. Apart from a higher than expected rate of infusion reactions, no other unexpected toxicities were observed. No differences in serum TGF-α or urinary PGE-M between cycles were seen, suggesting that the appropriate targets may not have been hit.

Background: Laparoscopic left pancreatectomy (LLP) is associated with favorable outcomes compared with open left pancreatectomy (OLP). However, it is unclear if the risk factors associated with operative morbidity differ between these two techniques. Guidelines for determining which patients should undergo OLP versus LLP do not exist., Methods: A multi-institutional analysis of OLP and LLP performed in 9 academic medical centers was undertaken. LLP cases were defined in an intent-to-treat manner. Perioperative variables were analyzed to identify factors associated with complications and pancreatic fistulae after OLP and LLP. In addition, complication and fistula rates for patients undergoing OLP and LLP were compared in matched cohorts to determine if one approach resulted in superior outcomes over the other., Results: Six hundred and ninety-three left pancreatectomy cases (439 OLP, 254 LLP) were analyzed. OLP and LLP cases were similar with respect to patient age and American Society of Anesthesiologists score. Body mass index (BMI) was higher in patients undergoing LLP. OLP was more often performed for adenocarcinoma and larger tumors, resulted in longer resected specimen lengths, and more commonly involved concomitant splenectomy. Estimated blood loss was higher and operative times were longer during OLP. On multivariate analysis, variables associated with major complications and clinically significant fistulae differed between OLP and LLP. Patients with body mass index ≤27, without adenocarcinoma, and with pancreatic specimen length ≤8.5 cm had significantly higher rates of significant fistulae after OLP than after LLP; in contrast, no preoperatively evaluable variables were associated with a higher likelihood of significant fistula after LLP versus OLP., Conclusions: Risk factors for complications and pancreatic fistulae after left pancreatectomy differ when open versus laparoscopic techniques are employed. Preoperative characteristics may identify cohorts of patients who will benefit more from LLP, and no patient cohorts had higher postoperative complication rates after LLP than OLP. These observations suggest that LLP may be the operative procedure of choice for most patients with left-sided pancreatic lesions; a more definitive prospective and randomized comparison may be warranted., (@ 2011 Lippincott Williams & Wilkins, Inc.)

Objectives: To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience., Summary and Background Data: LLP is being performed more commonly with limited data comparing results with outcomes from OLP., Methods: Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression., Results: Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56)., Conclusions: In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.