Background: Mortality due to severe or necrotizing acute pancreatitis most often results from multiorgan dysfunction syndrome (MODS) occurring either early (within the first 14 days) or 2 weeks or more after the onset of symptoms due to septic complications. The aim of this study was to analyse the course of the disease in patients who died from severe acute pancreatitis. Methods: Between January 1994 and August 2000 details of 263 consecutive patients with acute pancreatitis were entered prospectively into a database. All patients were treated in an intermediate or intensive care unit. Results: The overall mortality rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten of 106) in patients with necrotizing disease. No patient died within the first 2 weeks of disease onset. The median day of death was 91 (range 15–209). Six patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health Evaluation (APACHE) II score during the first week of disease, pre-existing co-morbidity, body mass index, infection and extent of necrosis were significantly associated with death (P < 0·01 for all parameters). However, only infection of the necrotic pancreas was an independent risk factor in the multivariate analysis. Conclusion: Early deaths in patients with severe acute pancreatitis are rare, mainly as a result of modern intensive care treatment. Nine of the ten deaths occurred more than 3 weeks after disease onset. Infection of pancreatic necrosis was the main risk factor for death.

Purpose: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. Experimental Design: A well-characterized PDAC cohort (n = 110) underwent next-generation sequencing with a hot spot cancer panel while next-generation tissue microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM), and DNA mismatch repair proteins. Previous data on FOXP3 were integrated. Immune cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8th edition, 2017), survival, and epithelial–mesenchymal transition (EMT)–like tumor budding. Results: Three PDAC subtypes were identified: the “immune escape” (54%), poor in T and B cells and enriched in FOXP3⁺ regulatory T cells (Treg), with high-grade budding, frequent CDKN2A, SMAD4, and PIK3CA mutations, and poor outcome; the "immune rich" (35%), rich in T and B cells and poorer in FOXP3⁺ Tregs, with infrequent budding, lower CDKN2A and PIK3CA mutation rate, and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11 and ATM), and the best outcome; and the "immune exhausted" (11%), with immunogenic microenvironment and two subpopulations—one with PD-L1 expression and a high PIK3CA mutation rate and a microsatellite-unstable subpopulation with a high prevalence of JAK3 mutations. The combination of low budding, low stromal FOXP3 counts, presence of TLTs, and absence of CDKN2A mutations confers significant survival advantage in patients with PDAC. Conclusions: Immune host responses correlate with tumor characteristics, leading to morphologically recognizable PDAC subtypes with prognostic/predictive significance. Clin Cancer Res; 24(18); 4444–54. ©2018 AACR. See related commentary by Khalil and O'Reilly, p. 4355

Background: Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)–adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. Results: One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). Conclusions: We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

SEVERE ACUTE pancreatitis is still a life-threatening disease. Most advances in the management of severe acute pancreatitis have arisen from general improvements in intensive care and organ system support.^1,2 Septic complications occurring after the first 10 to 14 days of the disease are the most frequent cause of death in patients with pancreatic necrosis.^3-5 Thus, infection of pancreatic or peripancreatic tissue is recognized as the single most important determinant of morbidity and mortality associated with severe necrotizing pancreatitis.^4,6-8 During the natural course of acute pancreatitis, bacterial infection is reported to develop in 40% to 70% of all patients with necrotizing disease.^9-11 Therefore, special interest has been focused on prophylactic administration of antibiotics, based on the hypothesis that reduction of late pancreatic infection will decrease morbidity and mortality. Early studies on prophylactic intravenous antibiotic treatment failed to show any favorable effect on the outcome of patients with acute pancreatitis, either because patients with mild disease were included or ineffective antibiotic regimens were used.^12-14 On the other hand, recent controlled clinical studies support the use of early antibiotic treatment in patients with severe disease.^15-19 A meta-analysis of these studies showed a positive benefit for antibiotics in reducing mortality when broad-spectrum antibiotics with proven pancreatic tissue penetration were used.²⁰ Hence, routine early antibiotic treatment in all patients with necrotizing acute pancreatitis was recommended.²¹ However, widespread use of antibiotics may lead to an increased number of multiresistant bacterial and fungal infections, thereby worsening the course of the disease and the outcome. In this study, we report microbiological findings in patients who received prophylactic antibiotic treatment and analyze the influence of antibiotic treatment on the time point of infection, the type of organisms cultured from these patients, and the patient's outcome.

To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.