Innate lymphoid cells (ILC)-22 protect the intestinal mucosa from infections by secreting interleukin-22 (IL-22). They include NKp46+ and Lymphoid Tissues inducer (LTi)-like subsets. Both express the aryl-hydrocarbon receptor (AHR), a sensor for environmental, dietary and endogenous aromatic compounds. We show that AHR-/- mice have a marked ILC22 deficit, resulting in diminished IL-22 secretion and inadequate protection against intestinal bacterial infections. AHR-/- mice also lack post-natally-imprinted cryptopatches (CP) and isolated lymphoid follicles (ILF), but not embryonically-imprinted Peyer's Patches (PP). AHR induces Notch, which is required for NKp46+ILC, while LTi-like ILC, CP and ILF are partially dependent on Notch signaling. These results establish that AHR is essential for ILC22 and post-natal intestinal lymphoid tissues and reveal heterogeneity of ILC22 subsets in their developmental requirements and their impact on the generation of intestinal lymphoid tissues.

A B S T R A C T PurposeRecent studies have reported increased mortality for right-sided colon cancers but had limited adjustment for patient characteristics and conflicting results by stage. We examined the relationship between colon cancer location (right-v left-side) and 5-year mortality by stage. Patients and MethodsWe identified Medicare beneficiaries from 1992 to 2005 with American Joint Commission on Cancer stages I to III primary adenocarcinoma of the colon who underwent surgery for curative intent through Surveillance, Epidemiology, and End Results (SEER) -Medicare data. Adjusted hazard ratios (HRs) and 95% CIs for predictors of all-cause 5-year mortality were obtained by using Cox proportional hazards regression. ResultsOf 53,801 patients, 67% had right-sided colon cancer. Patients with right-sided cancer were more likely to be older, to be women, to be diagnosed with a more advanced stage, and to have more poorly differentiated tumors. Adjusted Cox regression showed no significant difference in mortality between right-and left-sided cancers for all stages combined (HR, 1.01; 95% CI, 0.98 to 1.04; P ϭ .598) or for stage I cancers (HR, 0.95; 95% CI, 0.88 to 1.03; P ϭ .211). Stage II right-sided cancers had lower mortality than left-sided cancers (HR, 0.92; 95% CI, 0.87 to 0.97; P ϭ .001), and stage III right-sided cancers had higher mortality (HR, 1.12; 95% CI, 1.06 to 1.18; P Ͻ .001). ConclusionWhen analysis was adjusted for multiple patient, disease, comorbidity, and treatment variables, no overall difference in 5-year mortality was seen between right-and left-sided colon cancers. However, within stage II disease, right-sided cancers had lower mortality; within stage III, right-sided cancers had higher mortality.

Epstein-Barr virus (EBV) has been causally associated with at least five human malignancies. The exact contributions made by EBV to these cancers remain unknown. We demonstrate that one viral protein found in all EBV-associated malignancies, Epstein-Barr nuclear antigen 1 (EBNA-1), is required for survival of one of these cancers, EBV-positive Burkitt's lymphoma. Inhibition of EBNA-1 decreases survival of these tumor cells by inducing apoptosis. Expression of EBNA-1 in uninfected cells also can inhibit apoptosis induced by expression of p53 in the absence of the EBV genome. Our findings demonstrate that EBNA-1 is critical for the continued survival of EBV-associated Burkitt's lymphoma, and, by extension, for the other B cell tumors with which EBV is associated. Efficient inhibitors of EBNA-1's functions would likely prove useful in the therapy of EBV-associated malignancies.

Importance No consensus exists regarding the definition of “high risk” surgery in older adults. An inclusive and precise definition of high risk surgery may be useful for surgeons, patients, researchers and hospitals. Objectives To develop a list of “high risk” operations. Design 1) Retrospective cohort study; and 2) Modified Delphi procedure. Setting All Pennsylvania acute care hospitals (Pennsylvania Health Care Cost Containment Council [PHC4], 2001–2007) and a nationally-representative sample of U.S. acute care hospitals (Nationwide Inpatient Sample [NIS], HCUP, AHRQ 2001–2006). Patients Admissions 65 and older to PHC4 hospitals and admissions 18 and older to NIS hospitals. Methods We identified ICD-9 CM procedure codes associated with >1% inpatient mortality in PHC4. We used a modified Delphi technique with 5 board certified surgeons to further refine this list by excluding non-operative procedures and operations that were unlikely to be the proximate cause of mortality and were instead a marker of critical illness (e.g., tracheostomy). We then cross-validated this list of ICD-9CM codes in the NIS. Main Outcomes Measures 1) Delphi consensus of at least 4/5 panelists; 2) proportion agreement in the NIS. Results Among 4,739,522 admissions 65 and older in PHC4, 2,569,589 involved a procedure, encompassing 2,853 unique procedures. Of 1,130 procedures associated with a crude inpatient mortality of at least 1%, 264 achieved consensus as high risk operations by Delphi. The observed inpatient mortality in the NIS was ≥ 1% for 227/264 (86%) of the procedures in patients age 65 and older. The pooled inpatient mortality rate for these identified high risk procedures performed on patients age ≥65 was double the inpatient mortality for correspondingly identified high risk operations for patients less than 65 (6% vs. 3%). Conclusions We developed a list of procedure codes that can be used to identify “high risk” surgical procedures in claims data. This list of “high risk” operations can be used to standardize the definition of high risk surgery in quality and outcomes-based studies and design targeted clinical interventions.

Objective Patient satisfaction with the health care experience has become a top priority for Centers for Medicare and Medicaid Services. With resources and efforts directed at patient satisfaction, we evaluated whether high patient satisfaction measured by HCAHPS surveys correlates with favorable outcomes. Methods Medical centers were identified from the University HealthSystem Consortium database from 2011–2012. Variables included hospital characteristics, process measure compliance, and surgical outcomes. Chi-squared analysis was used to evaluate for variables associated with high patient satisfaction (defined as hospitals that scored above the 50th percentile of top box scores). Results We identified 171 hospitals with complete data. The following variables were significantly associated with high overall patient satisfaction: large hospitals, high surgical volume, and low mortality (p < 0.001). Compliance with process measures and patient safety indicators, as well as length of stay, did not correlate with overall satisfaction. The presence of complications (p = 0.491) or increased rate of readmission (p = 0.056) were not found to affect patient satisfaction. Low mortality index was consistently found to be associated with high satisfaction across 9 of 10 HCAHPS domains. Conclusions We found that hospital size, surgical volume and low mortality were associated with high overall patient satisfaction. However, with the exception of low mortality, favorable surgical outcomes were not consistently associated with high HCAHPS scores. With existing satisfaction surveys, we conclude that factors outside of surgical outcomes appear to influence patients' perceptions of their care.

Vascular occlusion combined with radiofrequency ablation increases the volume of necrosis, creates a more spherical lesion, and increases the time tissue is exposed to lethal temperatures when compared with radiofrequency alone. Most of this vascular occlusion effect could be accomplished with hepatic artery occlusion alone.

When controlled for probability of morbidity, laparoscopy decreases the rate of postoperative complications. Given the equivalent outcomes of laparoscopic approaches, we conclude that laparoscopy should be offered to all patients who lack an absolute contraindication for laparoscopic surgery.

Objective The objective of this study was to identify risk factors for delays in chemotherapy after rectal cancer surgery and evaluate the effects of delayed therapy on long term outcomes. We also sought to clarify what time frame should be used to define delayed adjuvant chemotherapy. Background Postoperative complications have been found to influence timing of chemotherapy in colon cancer patients. Delays in chemotherapy have been shown to be associated with worse overall and disease free survival in colorectal cancer patients, although timing of delay has not been agreed upon in the literature. Study Design We performed a retrospective review of a prospectively maintained rectal cancer database. Univariate analysis was used to identify risk factors for delayed chemotherapy. Kaplan Meier curves were generated to compare overall and disease free survival in patients based on complications and timing of chemotherapy. Settings This study was performed at the University of Wisconsin Hospital, Madison, WI between 1995 and 2012. Patients Patients with rectal cancer who underwent proctectomy with curative intent were included in this study. Outcome Measures Timing of chemotherapy, 30 day complications and 30 day readmissions were the main outcome measures. Results Postoperative complications and 30 day readmissions were associated with delays in chemotherapy ≥ 8 weeks after surgery. Patients who received chemotherapy ≥ 8 weeks postoperatively were found to have worse local and distant recurrence rates and worse overall survival as compared with patients who received chemotherapy within 8 weeks of surgery. Limitations Limitations of this study include its retrospective nature and that it was performed at a single institution. Conclusions We found complications and readmissions to be risk factors for delayed chemotherapy. Patients who received therapy ≥ 8 weeks postoperatively had worse disease free and overall survival.