Anastomotic leakage after curative rectal cancer resection has no impact on long-term survival: a propensity score analysis

Purpose: Anastomotic leakage (AL) is a severe and frequent complication of rectal cancer resection, with an incidence rate of approximately 9%. Although the impact of AL on morbidity and short-term mortality has been established, the literature is contradictory regarding its influence on long-term, cancer-specific survival. The present investigation assessed the long-term survival of 584 patients with stage I-III rectal cancer. Methods: The 10-year overall survival and cancer-specific survival were analyzed in 584 patients from a single tertiary center. All patients had undergone curative rectal cancer resection between 1991 and 2010. Patients with and without AL were compared using both a multivariate Cox hazards model and propensity score analysis. Results: A total of 64 patients developed AL (11.0%, 95% confidence interval (CI) = 8.7 to 13.8%). The median follow-up was 5.2years for all patients; and 7.4years for patients still alive at the end of the investigated period. AL did persistently not impair cancer-specific survival based on unadjusted Cox regression (hazard ratio of death (HR) = 1.27, 95% CI = 0.65 to 2.48, P = 0.489); risk-adjusted Cox regression (HR = 1.10, 95% CI = 0.54 to 2.20, P = 0.799); and propensity score matching (HR = 1.18, 95% CI = 0.57 to 2.43, P = 0.660). Conclusions: Based on the present propensity score analysis, the oncologic outcomes in patients undergoing curative rectal cancer resections were not impaired by the development of anastomotic leakage

Survival after Abdominoperineal and Sphincter-Preserving Resection in Nonmetastatic Rectal Cancer: A Population-Based Time-Trend and Propensity Score-Matched SEER Analysis

Background. Abdominoperineal resection (APR) has been associated with impaired survival in nonmetastatic rectal cancer patients. It is unclear whether this adverse outcome is due to the surgical procedure itself or is a consequence of tumor-related characteristics. Study Design. Patients were identified from the Surveillance, Epidemiology, and End Results database. The impact of APR compared to coloanal anastomosis (CAA) on survival was assessed by Cox regression and propensity-score matching. Results. In 36,488 patients with rectal cancer resection, the APR rate declined from 31.8% in 1998 to 19.2% in 2011, with a significant trend change in 2004 at 21.6% (P<0.001). To minimize a potential time-trend bias, survival analysis was limited to patients diagnosed after 2004. APR was associated with an increased risk of cancer-specific mortality after unadjusted analysis (HR = 1.61, 95% CI: 1.28–2.03, P<0.01) and multivariable adjustment (HR = 1.39, 95% CI: 1.10–1.76, P<0.01). After optimal adjustment of highly biased patient characteristics by propensity-score matching, APR was not identified as a risk factor for cancer-specific mortality (HR = 0.85, 95% CI: 0.56–1.29, P=0.456). Conclusions. The current propensity score-adjusted analysis provides evidence that worse oncological outcomes in patients undergoing APR compared to CAA are caused by different patient characteristics and not by the surgical procedure itself

Reconstructing Syria: Resettling Refugees and Internally Displaced Persons

This report examines the key issues impacting the resettlement of Syrian refugees and IDPs. Many indicators point to the civil war in Syria reaching an end with Bashar al-Assad’s regime still in power. As of December 2018, 11 million Syrians are displaced, 5.6 of whom have fled the country and become refugees. The other 6.2 million still reside within the country (Mercy Corps, 2018). Although the eight years of violence and war is coming to an end, many regions of Syria are unsuitable for resettlement. Prior to 2011, various ethnic and religious groups peacefully coexisted within Syria. With the rise of Assad leading up to the civil war, these groups began fracturing and the sectarian divisions positioned groups against one another. Resettling displaced Syrians in their places of origin poses challenges because of these divisions. Alawites and Druze are now extremely vulnerable to persecution due to their minority status. The Kurds are at odds with Turkey as they continue to desire an autonomous state. The Assad regime has empowered the Alawites who were historically persecuted due to their faith. As the war is winding down, ISIS has lost substantial territory and Assad is positioned to claim victory

Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria

Simple Summary Eye tumors in children are very rare. In Europe, these eye tumors are nearly always diagnosed early and cure rates are high. However, eye tumors in childhood often occur as the first sign of a genetic tumor predisposition syndrome. This study collected data of children with malignant eye tumors diagnosed in five years in Germany and Austria to learn about the association of eye tumors in childhood with tumor predisposition syndrome. The study recruited 300 children with malignant eye tumors in childhood. In the here-presented cohort, more than 40% of eye tumors were associated with rare tumor predisposition syndromes. For this reason, all children with eye tumors and their families should receive genetic counseling for a tumor predisposition syndrome. Children with a genetic predisposition to cancer should receive a tailored surveillance, including detailed history, physical examination and, if indicated, imaging to screen for other cancers later in life. Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity(1). Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified(2,3). WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens(4). SHH tumours show hedgehog pathway activation, and have an intermediate prognosis(2). Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges(2,3,5). The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patient

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

International audienceALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity