ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining.

Ataxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double-stranded breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Ablating phosphorylation at T4102 attenuates DNA-PKcs kinase activity and this destabilizes the interaction between DNA-PKcs and the Ku-DNA complex, resulting in decreased assembly and stabilization of the NHEJ machinery at DSBs. Phosphorylation at T4102 promotes NHEJ, radioresistance, and increases genomic stability following DSB induction. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PKcs.

Tumor Biology Impacts Survival in Surgically Managed Primary Hepatic Vascular Malignancies.

BACKGROUND: Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database. MATERIALS AND METHODS: In a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified. RESULTS: Three hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P< 0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival. CONCLUSIONS: In this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

Predictors and outcomes of converted minimally invasive pancreaticoduodenectomy: a propensity score matched analysis.

BACKGROUND: Data-driven patient selection guidelines are not available to optimize outcomes in minimally invasive pancreaticoduodenectomy (MIPD). We aimed to define risk factors associated with conversion from MIPD to open PD and to determine the impact of conversion on post-operative outcomes. METHODS: We conducted a retrospective review of MIPD using NSQIP from 2014 to 2015. Propensity score was used to match patients who underwent completed MIPD to converted MIPD. RESULTS: 467 patients were included: 375 (80.3%) MIPD and 92 (19.7%) converted. Converted patients were more often male (64% vs. 52%, p = 0.030), had higher rates of dyspnea (10% vs. 3%, p = 0.009), underwent more vascular (44% vs. 14%, p < 0.001) or multivisceral resection (19% vs. 6%, p = 0.0005), and were more likely attempted laparoscopically compared to robotically (76% vs. 51%, p < 0.001). Robotic approach was independently associated with reduced risk of conversion (OR 0.40, 95% CI 0.23-0.69), while male gender (OR 1.70, 95% CI 1.02-2.84), history of dyspnea (OR 3.85, 95% CI 1.49-9.96), vascular resection (OR 4.32, 95% CI 2.53-7.37), and multivisceral resection (OR 2.18, 95% CI 1.05-4.52) were associated with increased risk. Major complications were more common in converted patients (68% vs. 37%, p < 0.001). Converted patients had increased odds of non-home discharge (OR 3.25, 95% CI 1.06-9.97) and an associated increased length of stay of 3 days (95% CI 0.1-6.7). CONCLUSION: Patients with a history of dyspnea or tumors requiring vascular or multivisceral resection were at increased risk of conversion, and the robotic platform was associated with a lower rate of conversion. Conversion was independently associated with increased overall complications, increased length of stay, and non-home discharge.

Adjuvant Therapy is Associated with Improved Survival in pT1N1 Gastric Cancer in a Heterogeneous Western Patient Population.

BACKGROUND: Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We established the prognostic utility of lymph node status, determined the pattern of use of AT, and compared survival stratified by type of AT in pT1N1 GAC in a Western patient population. METHODS: We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. RESULTS: We compared 4516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p < 0.001), more often poorly differentiated (56.2% vs. 39.6%, p < 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p < 0.001) compared with pT1N0. pT1N1 was associated with worse median overall survival (OS) (6.9 vs. 9.9 years for pT1N0, p < 0.001). pN1 was independently associated with worse OS (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.84-2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65-0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22-0.65 and HR 0.40, 95% CI 0.28-0.57). CONCLUSIONS: pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients.

Non-home Discharge and Prolonged Length of Stay After Cytoreductive Surgery and HIPEC.

BACKGROUND: Predictive models for nonhome discharge (NHD) have been proposed in major surgical specialties. The rates and risk factors associated with NHD and prolonged length of stay (PLOS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have not been evaluated. The aim of this study is to identify risk factors for NHD and PLOS after CRS/HIPEC in a national cohort of patients. MATERIALS AND METHODS: CRS/HIPEC cases were identified from the National Surgical Quality Improvement Program 2011-2012 data set. Patients with an NHD or PLOS (>30 d) were compared with a group of patients discharged to home within 30 d. Univariate analysis was used to compare patient characteristics, operative variables, and postoperative complications among both groups. Multivariate regression analysis was used to identify independent predictors of NHD and PLOS. RESULTS: Five hundred fifty-six patients undergoing CRS/HIPEC were identified, of which 44 (7.9%) were not discharged to home within 30 d. The rate of NHD and PLOS in this cohort was 4.1% and 3.7%, respectively. Multivariate analysis identified age ≥65 y, pre-op albumin <3.0 g/dL, and having a multivisceral resection as independent predictors of NHD/PLOS. If all three predictors are met preoperatively, the probability of NHD/PLOS was calculated to be 30.2%. CONCLUSIONS: The main risk factors for NHD/PLOS after CRS/HIPEC were advanced age, hypoalbuminemia, and multivisceral resection. Adequate identification of these risk factors may facilitate preoperative discussion with patients, and improve discharge planning and resource utilization.

Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012.

BACKGROUND AND OBJECTIVES: Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. METHODS: PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. RESULTS: The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). CONCLUSION: Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT.

Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-matched Study From a National Cohort of Patients.

OBJECTIVE: To compare the perioperative outcomes of minimally invasive pancreaticoduodenectomy (MIPD) in comparison with open pancreaticoduodenectomy (OPD) in a national cohort of patients. BACKGROUND: Limited well-controlled studies exist comparing perioperative outcomes between MIPD and OPD. METHODS: Patients who underwent MIPD and OPD were abstracted from the 2014 to 2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. OPD and MIPD patients were matched 3:1 using propensity score, and perioperative outcomes were compared. RESULTS: A total of 4484 patients were identified with 334 (7.4%) undergoing MIPD. MIPD patients were younger, more likely to be White, and had a lower rate of weight loss. They were more likely to undergo classic Whipple and to have a drain placed. After 3:1 matching, 1002 OPD patients were compared with 334 MIPD patients. MIPD was associated with longer mean operative time (426.6 vs 359.6 minutes; P < 0.01), higher readmission rate (19.2% vs 14.3%; P = 0.04) and lower rate of prolonged length of stay >14 days (16.5% vs 21.6%; P = 0.047). The 2 groups had a similar rate of 30-day mortality (MIPD 1.8% vs OPD 1.3%; P = 0.51), overall complications, postoperative pancreatic fistula, and delayed gastric emptying. A secondary analysis comparing MIPD without conversion or open assist with OPD showed that MIPD patients had lower rates of overall surgical site infection (13.4% vs 19.6%; P = 0.04) and transfusion (7.9% vs 14.4%; P = 0.02). CONCLUSIONS: MIPD had an equivalent morbidity and mortality rate to OPD, with the benefit of a decreased rate of prolonged length of stay, though this is partially offset by an increased readmission rate.

Comparison of Overall Survival Between Preoperative Chemotherapy and Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma.

Background: Preoperative therapy is being increasingly used in the treatment of resectable pancreatic cancer. Because there are only limited data on the optimal preoperative regimen, we compared overall survival (OS) between preoperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) in resectable pancreatic adenocarcinoma. Patients and Methods: Patients receiving preoperative therapy and resection for clinical T1-3N0-1M0 adenocarcinoma of the pancreas were identified in the National Cancer Database for 2006 through 2012. We constructed inverse probability of treatment weights to balance baseline group differences, and compared OS between CT and CRT, as well as pathologic and postoperative findings. Results: We identified 1,326 patients (CT: 616; CRT: 710). Differences in OS were not significant between CRT and CT (median survival, 25 vs 26 months; P=.10; weight-adjusted hazard ratio, 0.89; 95% CI, 0.77-1.02). Compared with patients in the CT group, those in the CRT group had lower pathologic T stage (ypT0/T1/T2: 36% vs 21%; P<.01), less lymph node involvement (ypN1: 35% vs 59%; P<.01), and fewer positive resection margins (14% vs 21%; P=.01), but had more postoperative unplanned readmissions (9% vs 6%; P=.01) and increased 90-day mortality (7% vs 4%; P=.03). Those in the CRT group were also less likely to receive postoperative therapy (26% vs 51%; P<.01). Conclusions: Preoperative CT and CRT have similar OS, but CRT is associated with more favorable pathologic features at the cost of higher postoperative morbidity and mortality. Additional trials investigating preoperative therapy are needed for patients with resectable pancreatic cancer.

Racial and ethnic disparities in a national cohort of ampullary cancer patients.

BACKGROUND AND OBJECTIVES: Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. METHODS: Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. RESULTS: A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. CONCLUSIONS: Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors.

Comparative outcomes of adenosquamous carcinoma of the pancreas: An analysis of the National Cancer Database.

BACKGROUND: A paucity of data exists regarding the natural history and outcome measures of adenosquamous carcinoma of the pancreas (ASCP), a histology distinct from pancreatic adenocarcinoma (PDAC). The aim of this study is to characterize the clinicopathological features of ASCP in a large cohort of patients comparing outcome measures of surgically resected patients to PDAC. METHODS: We identified patients diagnosed with ASCP or PDAC from the National Cancer Database from 2004 to 2012. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. RESULTS: We identified 207 073 patients: 205 328 (99%) in the PDAC group and 1745 (1%) in the ASCP group. ASCP tumors were larger, located more frequently in a body/tail location (36% vs 24%, P < 0.001), undifferentiated/anaplastic histology (41% vs 17%, P < 0.001), and early stage presentation, (39% vs 32%, P < 0.001). There was no significant difference in OS when comparing all patients with PDAC and ASCP (6.2 months and 5.7 months, P = 0.601). In surgical patients ASCP histology was associated with worse OS (14.8 months vs 20.5 months, P < 0.001) but had lower nodal involvement (55% vs 61%, P < 0.001). ASCP histology was independently associated with worse OS, after adjusting for tumor characteristics, treatment, and patient demographics. In patients with only resected ASCP histology, negative lymph node status, R0 surgical resection, and receipt of chemotherapy was independently associated with improved overall survival following surgical resection. CONCLUSION: Although patients with ASCP and PDAC tumors have similar survival when non-surgical and surgical patients are combined, ASCP is associated with worse survival in stage I/II resected patients.

Conversion of Minimally Invasive Distal Pancreatectomy: Predictors and Outcomes.

BACKGROUND: Data on the risk factors for conversion during minimally invasive distal pancreatectomy (MIDP) and its effect on postoperative outcomes are limited. METHODS: This retrospective study used the pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program database to compare MIDP requiring unplanned conversion with completed MIDP and open distal pancreatectomy (ODP). RESULTS: Of the 2926 cases identified in this study, 48.8% had ODP, 42.8% had MIDP, and 7.9% had conversion to MIDP. The conversion rate was 15.3% overall, 17.3% for laparoscopic surgery, and 8.5% for robotic surgery (p < 0.001). The risk factors associated with conversion were higher body mass index (BMI), low preoperative albumin level, a current smoking habit, and malignant T3/T4 disease or chronic pancreatitis compared with benign tumor smaller than 5 cm. A robotic approach was associated with a lower adjusted conversion rate than laparoscopy (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.19-0.52). After adjustment, conversion was associated with a higher overall complication rate than MIDP (OR 1.89; 95% CI 1.35-2.66) or ODP (OR 1.41; 95% CI 1.00-1.98). CONCLUSIONS: Chronic pancreatitis, large malignant tumors, higher BMI, lower serum albumin, and a current smoking habit were shown to be independent risk factors for conversion during MIDP. A robotic approach was associated with a lower conversion rate than laparoscopic MIDP. Conversion of MIDP was associated with a higher overall complication rate than completed MIDP or ODP. Adequate patient selection for MIDP may prevent conversion and associated increased morbidity.

The Yield of Staging Laparoscopy in Gastric Cancer is Affected by Racial and Ethnic Differences in Disease Presentation.

BACKGROUND: Gastric cancer is a heterogeneous disease with variable presentation between racial and ethnic groups. Staging laparoscopy (SL) detects occult metastases not visible on cross-sectional imaging and therefore improves staging. It remains unclear how differences in race and ethnicity affect disease presentation and the yield of SL. METHODS: We performed a retrospective review of a prospectively maintained database to identify patients with gastric cancer treated with curative intent at our institutions from 2008 to 2015. RESULTS: Hispanic patients presented at an earlier mean age (55.5 ± 11.9 years) compared with Asian (59.8 ± 13.9 years), African American (61.0 ± 10.0 years), and white patients (61.7 ± 12.5 years; p = 0.046) and with more locally advanced disease (clinical stage T3/T4 or node positive; Hispanic 87%; African American 79%; white 68%, Asian 55%; p = 0.03). SL identified 42 patients (34%) with occult metastatic disease. Hispanics were more likely to have a positive SL (44%) than white patients (21%; p = 0.04). On univariate analysis, Hispanic ethnicity, clinical T3/T4, positive nodal disease, signet ring cells, and poor differentiation were predictors of a positive SL. On multivariable analysis, clinical T3/T4, signet ring cells, and poor differentiation independently predicted radiographically occult disease. CONCLUSIONS: Hispanic patients presented with more locally advanced disease and were more likely to have occult disease found on SL compared with white patients. Laparoscopy should be used routinely as part of the pretreatment staging evaluation for patients with locally advanced disease as it alters the management in a significant proportion of patients.

Failure to rescue following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can significantly improve the survival in selected patients with peritoneal carcinomatosis. This study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR), mortality following postoperative complications from CRS/HIPEC. METHODS: Patients suffering a complication following CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program data set. FTR was defined as 30-d mortality in the setting of a complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR). Predictors of FTR were identified using a multivariable logistic regression model. RESULTS: A total of 915 eligible CRS/HIPEC cases were identified. In all, 382 patients (42%) developed ≥1 postoperative complication, and 88 patients (10%) suffered ≥1 major complication. Seventeen patients died following a complication, amounting to an FTR rate of 4%. FTR patients were more likely than non-FTR patients to have dependent functional status (18% versus 2%, P = 0.01), have American Society of Anesthesiologists (ASA) class 4 status (29% versus 8%, P = 0.01), develop ≥3 complications (65% versus 24%, P < 0.01), and suffer a major complication (94% versus 20%, P < 0.01). The following were independently associated with FTR: ASA class 4 (odds ratio [OR]: 13.4, 95% confidence interval [CI], 1.2-146.8) and major complications (OR: 66.0, 95% CI, 8.4-516.6). CONCLUSIONS: ASA class 4, major morbidity, and likely dependent functional status are independent predictors of FTR following CRS/HIPEC to treat peritoneal carcinomatosis. Therefore, ASA class 4 and dependent functional status should be considered as contraindications for CRS/HIPEC and only offered in highly selective cases.

Nomogram to predict non-home discharge following pancreaticoduodenectomy in a national cohort of patients.

BACKGROUND: Despite the development of pathways to enhance recovery and discharge to home, a significant proportion of patients are discharged to inpatient facilities after pancreaticoduodenectomy (PD). The aim of this study was to determine the rate of non-home discharge (NHD) following PD in a national cohort of patients and to develop predictive nomograms for NHD. METHODS: The National Surgical Quality Improvement Program was used to construct and validate pre- and postoperative nomograms for NHD following PD. RESULTS: A total of 6856 patients who underwent PD were identified, of which 927 (13.5%) had an NHD. The independent preoperative predictors of NHD were being female, older age, higher BMI, low serum albumin, >10% weight loss, ASA class III/IV, and being diagnosed with a bile duct/ampullary neoplasm or neuroendocrine tumor. A preoperative nomogram was constructed with a concordance index of 0.77. When postoperative variables were added to the model, the concordance index increased to 0.82. The postoperative predictors of NHD were return to the operating room, length of stay of ≥14 days, and any inpatient complications. CONCLUSIONS: These nomograms could be useful risk assessment tools to predict NHD after PD and therefore facilitate patient counseling and improve resource utilization and discharge planning.

B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.

T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were re-exposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.

B7-H4-deficient mice display augmented neutrophil-mediated innate immunity.

B7-H4 is an immunoglobulin superfamily molecule and shown to be inhibitory for T-cell responses. To explore physiologic roles of B7-H4, we created B7-H4-deficient (KO) mice by genetic targeting. B7-H4KO mice are healthy and their T- and B-cell responses to polyclonal antigens are in normal range. However, B7-H4KO mice are more resistant to infection by Listeria monocytogenes than their littermates. Within 3 days after infection, bacterial colonies in livers and spleens are significantly lower than the controls, suggesting a role of B7-H4 in enhancing innate immunity. Further studies demonstrate that neutrophils increase in peripheral organs of B7-H4KO mice more so than their littermates but their bactericidal functions remain unchanged. Augmented innate resistance is completely dependent on neutrophils, even in the absence of adaptive immunity. In vitro B7-H4 inhibits the growth of bone marrow-derived neutrophil progenitors, suggesting an inhibitory function of B7-H4 in neutrophil expansion. Our results identify B7-H4 as a negative regulator of the neutrophil response to infection and provide a new target for manipulation of innate immunity.

A comparative analysis of outcomes of open, laparoscopic, and robotic elective (procto-) colectomies for benign and malignant disease.

Laparoscopy has emerged as a common alternative to the open approach for colorectal operations. Robotic surgery has many advantages, but cost and outcomes are an area of study. There are no randomized-controlled trials of all techniques. The present study evaluated a cohort of veterans undergoing (procto-) colectomy for benign or malignant colorectal disease. This is a single-institution retrospective review. We compared open, laparoscopic, and robotic colectomies. The primary outcome was 30-day mortality. The secondary endpoints included morbidity, operative times, estimated blood loss (EBL), length of stay (LOS), conversion rate, and the learning curve (LC). Subgroup analyses were undertaken for: (1) right hemicolectomies (RHC) and (2) by specific surgeons most familiar with each approach. The cohort included 390 patients (men = 95%, White = 70.8%, BMI = 29.3 ± 6.4 kg/m2, age = 63.7 ± 10.2 years) undergoing (open = 117, laparoscopic = 168, and robotic = 105), colorectal operations for colorectal adenocarcinoma (52.8%) and benign disease. Thirty-day morbidity was similar across all techniques (open = 46.2%, laparoscopic = 42.9%, and robotic = 38.1%; NS). EBL and LOS were decreased with minimally invasive techniques compared to open. Operative time was longer in robotic, but equalized to laparoscopic after 90 cases. The learning curve was reduced to 20 when performed by the surgeon most familiar with the robot. EBL and operative time independently predicted complications for the entire cohort. The best technique for colorectal operations rests on the surgeon's experience, but minimally invasive techniques are gaining momentum over open colectomies. Robotic colectomy is emerging as a non-inferior approach to laparoscopy in terms of outcomes, while maintaining all its technical advantages.

Neuroendocrine Tumors in Meckel's Diverticulum: Recommendation for Lymphadenectomy Regardless of Tumor Size Based on the NCDB Experience.

BACKGROUND: Meckel's diverticulum (MD) is an anomaly of the small intestine from which malignancy may arise. Among MD neoplasms, neuroendocrine tumors (NETs) are considered the most common. However, their metastatic potential and optimal surgical therapy remain ill-defined. METHODS: In a retrospective analysis of the National Cancer Database (2004-2015), patients with a diagnosis of MD malignancy were identified. Clinicopathologic factors were extracted and tumors arising in MD were compared. In the subgroup of patients with NET, the association between tumor factors and node involvement was investigated. RESULTS: Three hundred twenty primary MD malignancies were captured in the National Cancer Database, consisting of 280 (87.5%) NET. The median age at diagnosis was 64 years. Patients were predominantly male (207, 73.9%) and white (269, 96.1%). Most tumors were well-differentiated (118, 42.1%) and sub-centimeter (median size, 0.7 cm). Distant metastasis was present in a minority (16, 5.7%), and the median overall survival was 114 months in the entire cohort. The regional lymph node status was known in 87 NET patients, out of which 39 (44.8%) harbored node metastasis. Although the risk of node involvement increased with larger tumor size, it remained significant even among sub-centimeter (9 out of 34, 26.5%) and well-differentiated (18 out of 44, 41%) tumors. Regional node involvement was associated with the presence of distant metastasis (p < 0.001). CONCLUSION: Lymph node involvement was common irrespective of the size and grade of NET arising from Meckel's diverticulum. Therefore, regional lymphadenectomy should be considered in the curative-intent surgical management of these neoplasms regardless of tumor size and grade.

Determining the Adequate Examined Lymph Node Count in Resected Ampullary Adenocarcinoma-A National Cohort Study.

BACKGROUND: The evaluation of lymph node involvement is an essential component of cancer staging. Examining an inadequate number of lymph nodes potentially results in understaging. Current guidelines for lymph node retrieval for ampullary adenocarcinoma are based on data extrapolated from other periampullary malignancies and may not be applicable. The aim of this study was to determine the number of lymph nodes that should be examined in resection specimens to optimize staging in ampullary adenocarcinoma. METHODS: Patients with ampullary adenocarcinoma from 2004 to 2014 were identified in the National Cancer Database. We determined the minimum examined lymph node (ELN) count by modeling each potential ELN count from 2 to 30 in a multivariable regression analysis and confirmed the results with a sensitivity analysis. RESULTS: We identified 7451 patients of whom 52.2% had T3 or T4 disease and 51.4% had lymph node metastases. The median ELN count was 13 (interquartile range, 8-19). Increasing ELNs were independently associated with an increased likelihood of having positive nodal disease (odds ratio, 1.03; 95% confidence interval [CI], 1.03-1.04) and improved overall survival in both node-negative (hazard ratio [HR], 0.98; 95% CI, 0.97-0.99) and node-positive patients (HR, 0.99; 95% CI, 0.986-0.998). We determined that at least 17 lymph nodes should be examined. Overall survival for patients with 17 or more ELNs was superior than for those with fewer than 17 ELNs. CONCLUSION: Increasing ELNs were independently associated with improved overall survival in patients with resected ampullary adenocarcinoma. At least 17 lymph nodes should be examined for optimal nodal staging.

Robotic Versus Laparoscopic Pancreaticoduodenectomy: a NSQIP Analysis.

BACKGROUND: An increasing body of literature is supporting the safety of minimally invasive pancreaticoduodenectomy compared to open pancreaticoduodenectomy, but there are limited comparative studies between laparoscopic and robotic pancreaticoduodenectomy. The aim of this study was to compare the rate of postoperative 30-day overall complications between laparoscopic and robotic pancreaticoduodenectomy. METHODS: Patients who underwent laparoscopic and robotic pancreaticoduodenectomy were abstracted from the 2014-2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. A multivariable logistic regression model was developed to determine if the type of minimally invasive approach was associated with 30-day overall complications. RESULTS: We identified 428 minimally invasive pancreaticoduodenectomy cases, of which 235 (55%) were performed laparoscopically and 193 (45%) robotically. Patients who underwent the robotic approach were more likely to be white compared to those who underwent the laparoscopic approach and were less likely to have pulmonary disease, undergo preoperative radiotherapy, and have vascular and multivisceral resection. On multivariable analysis, we found that the type of minimally invasive approach, whether laparoscopic or robotic, was not associated with overall complications. The predictors of 30-day overall complications were higher body mass index (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.09), vascular resection (OR, 2.10; 95% CI, 1.23-3.58), and longer operative time (OR, 1.002; 95% CI, 1.001-1.004). CONCLUSIONS: Robotic pancreaticoduodenectomy was associated with a similar 30-day overall complication rate to laparoscopic pancreaticoduodenectomy. Further studies are needed to corroborate these findings and to establish the best approach to perform this complex operation.