A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients.

BACKGROUND: As patients with pancreas and periampullary cancer (PPC) experience improved survival rates and longevity, the focus shifts toward living life while surviving cancer. Fatigue is the most commonly reported symptom in all cancer patients. Exercise has been found to effectively decrease fatigue levels and improve physical functioning in cancer patients. STUDY DESIGN: One hundred two patients with resected PPC consented to participate in this study and were randomized to either an intervention group (IG) or a usual care group (UCG). Subjects completed visual analog scales, the FACIT-Fatigue Scale and the Short Form-36v2 after surgery and again 3 to 6 months after hospital discharge. RESULTS: Patients in the IG and UCG were comparable with regard to demographics, comorbidities, cancer type and staging, type of resection, preoperative fatigue and pain levels, adjuvant therapy, and baseline walking distance. Patients in the IG had significantly improved scores on the FACIT-Fatigue Scale at study completion, improved fatigue and pain scores, as well as overall physical functioning and mental health composite scores. At study completion, participants in the IG were walking twice as far and were significantly more likely to have continued walking or another form of exercise as compared with the UCG. Using hierarchical cluster analysis, 3 mutually exclusive symptom groupings were identified in the cohort. Kaplan-Meier survival analysis did not indicate an overall survival benefit for the IG. CONCLUSIONS: This is the first prospective, randomized controlled trial to report that participation in a home walking program confers a significant benefit in resected PPC patients with regard to fatigue levels, physical functioning, and health-related quality of life

Impact of Obesity on Perioperative Morbidity and Mortality Following Pancreaticoduodenectomy

Background: Obesity has been implicated as a risk factor for perioperative and postoperative complications. The aim of this study was determine the impact of obesity on morbidity and mortality in patients undergoing pancreaticoduodenectomy (PD). Study Design: Between January 2000 and July 2007, 262 patients underwent PD at Thomas Jefferson University Hospital (TJUH), of whom 240 had complete data, including body mass index (BMI) for analysis. Data on BMI, preoperative parameters, operative details, and post-operative course were collected. Patients were categorized as obese (BMI \u3e30 kg/m2), overweight (25≤BMI\u3c30), or normal weight (BMI\u3c25). Complications were graded according to previous published scales. Other endpoints included length of postoperative hospital stay, blood loss, and operative duration. Analyses were performed using univariate and multivariable models. Results: There were 103 (42.9%) normal weight, 71 (29.6%) overweight and 66 (27.5%) obese patients. There were 5 perioperative deaths (2.1%) with no differences across BMI categories. A significant difference in median operative duration and blood loss between obese and normal weight patients was identified (439vs. 362.5minutes, p= 0.0004; 650 vs. 500 ml, p=0.0139). Furthermore, median length of stay was marginally significantly longer for by BMI (9.5 vs. 8 days, p=0.095). While there were no significant differences in superficial wound infections, obese patients did have an increased rate of serious complications compared to normal weight patients (24.2% vs. 13.6%, respectively; p=0.10). Conclusions: Obese patients undergoing PD have a significantly increased blood loss and longer operative time, but do not have a significantly increased length of postoperative hospital stay or rate of serious complications. These findings should be considered when assessing patients for operation and when counseling patients regarding operative risk, but do not preclude obese individuals from undergoing definitive pancreatic surgery

Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution -- the first step in multi-disciplinary team building

Objective: This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery. Background: Pancreaticoduodenectomy (PD) is a complex general surgical procedure performed in varying numbers at many academic institutions. Originally associated with significant perioperative morbidity and mortality, multiple studies have now shown that this operation can be performed quite safely at high volume institutions that develop a particular expertise. Critical pathways are one of the key tools used to achieve consistently excellent outcomes as these institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with PD will result in performance gains and improved outcomes. Methods: Between January 1, 2004 and October 15, 2006 135 patients underwent PD, 44 before the implementation of a critical pathway on October 15, 2005, and 91 after. Perioperative and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes. Key aspects of the pathway include spending the night of surgery in the intensive care unit with careful attention to fluid balance, early mobilization on post-operative day one, aggressive early removal of encumbrances such as nasogastric tubes and urinary catheters, early post-operative feeding, and targeting discharge for postoperative day 6 or 7. Results: The pre- and post-pathway implementation groups were not statistically different with regards to age, sex, race, or pathology (malignant versus benign). Perioperative mortality, operative blood loss, and number of transfused units of packed red blood cells were also similar. As compared to the pre-pathway group, the post-pathway group had a significantly shorter postoperative length of stay (13 versus 7 days, P ≤ 0.0001), operative time (435 ± 14 minutes versus 379 ± 12 minutes, P ≤ 0.0001), and in room non-operative time (95 ± 4 minutes versus 76 ± 2 minutes, P ≤ 0.0001). Total hospital charges were significantly reduced from $240,242 ±$32,490 versus $126,566 ±$4883 (P ≤ 0.0001) after pathway implementation. Postoperative complication rates remained constant (44% pre-pathway versus 37% after, P = NS). Readmission rates were not negatively affected by the reduction in length of stay, with a 7% readmission rate prior to implementation and a 7.7% rate after implementation. Conclusion: Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources (greater OR and hospital bed availability) and overall cost containment. With a very conservative estimate of 75 pancreaticoduodenectomies per year by this group, this translates to a savings of 450 hospital days and over $8,550,000 in hospital charges on an annual basis. As we enter the pay for performance era, institutions will be required to generate such data in order to retain patient volumes, attract new patients, and receive incentive payments for high quality services rendered

Optimal technical management of stump closure following distal pancreatectomy: a retrospective review of 215 cases.

BACKGROUND: Pancreatic fistula (PF) is a major source of morbidity following distal pancreatectomy (DP). Our aim was to identify risk factors related to PF following DP and to determine the impact of technique of transection and stump closure. METHODS: We performed a retrospective review of 215 consecutive patients who underwent DP. Perioperative and postoperative data were collected and analyzed with attention to PF as defined by the International Study Group of Pancreatic Fistula. RESULTS: PF developed in 36 patients (16.7%); fistulas were classified as Grade A (44.4%), B (44.4%), or C (11.1%). The pancreas was transected with stapler (n = 139), cautery (n = 70), and scalpel (n = 3). PF developed in 19.8% of remnants which were stapled/oversewn and 27.7% that were stapled alone (p = 0.4). Of the 69 pancreatic remnants transected with cautery and oversewn, a fistula developed in 4.3% (p = 0.004 compared to stapled/oversewn; p = 0.006 compared to stapled/not sewn). The median length of postoperative hospital stay was significantly increased in patients who developed PF (10 vs. 6 days, p = 0.002) CONCLUSION: The method of transection and management of the pancreatic remnant plays a critical role in the formation of PF following DP. This series suggests that transection using electrocautery followed by oversewing of the pancreatic remnant has the lowest risk of PF

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN