Publications by authors named "Sajid A Khan"

48 Publications

Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma.

Eur J Cancer 2021 Jul 4;151:25-34. Epub 2021 May 4.

Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, CT, USA. Electronic address:

Objective: The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome affects immunity in human cancer. The purpose of this study was to investigate the association between intratumour bacteria, infiltrating CD8+ T cells and patient survival in cutaneous melanoma.

Methods: Using The Cancer Genome Altas's cutaneous melanoma RNA sequencing data, levels of intratumour bacteria and infiltrating CD8+ T cells were determined. Correlation between intratumour bacteria and infiltrating CD8+ T cells or chemokine gene expression and survival analysis of infiltrating CD8+ T cells and Lachnoclostridium in cutaneous melanoma were performed.

Results: Patients with low levels of CD8+ T cells have significantly shorter survival than those with high levels. The adjusted hazard ratio was 1.57 (low vs high) (95% confidence interval: 1.17-2.10, p = 0.002). Intratumour bacteria of the Lachnoclostridium genus ranked top in a positive association with infiltrating CD8+ T cells (correlation coefficient = 0.38, p = 9.4 × 10), followed by Gelidibacter (0.31, p = 1.13 × 10), Flammeovirga (0.29, p = 1.96 × 10) and Acinetobacter (0.28, p = 8.94 × 10). These intratumour genera positively correlated with chemokine CXCL9, CXCL10 and CCL5 expression. The high Lachnoclostridium load significantly reduced the mortality risk (p = 0.0003). However, no statistically significant correlation was observed between intratumour Lachnoclostridium abundance and the levels of either NK, B or CD4+ T cells.

Conclusion: Intratumour-residing gut microbiota could modulate chemokine levels and affect CD8+ T-cell infiltration, consequently influencing patient survival in cutaneous melanoma. Manipulating the intratumour gut microbiome may benefit patient outcomes for those undergoing immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.03.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184628PMC
July 2021

Occurrence and molecular characterization of on rice in Central Punjab, Pakistan.

J Nematol 2020 16;52. Epub 2021 Jan 16.

Department of Plant Pathology, University of Agriculture Faisalabad, P.O. Box 38040, Pakistan.

threatens global rice production, yet is understudied for many areas where it is cultivated. To better understand the prevalence and incidence of in central Punjab, Pakistan, we carried out field surveys of rice fields in the districts of Faisalabad and Chiniot. isolates were recovered from soil and root samples and identified on the basis of perineal patterns and rDNA ITS-based sequencing. The severity of nematode attack on rice roots and infested fields at various locations was based on galling index, root-knot nematode juveniles per root system, juveniles per 100 ml of soil, and prevalence of stylet-bearing nematodes and non-stylet-bearing nematodes. Maximum prevalence (22.5 and 27.5%) and minimum prevalence (17.5 and 20%) of was observed in Chiniot and Faisalabad, respectively. Eleven alternate host-plant species were examined in this study revealing varying degrees of infestation. ITS sequencing and phylogenetic analysis indicated that isolates from this study form a well-resolved clade with others from Asia, while another isolate falls outside of this clade in an unresolved polytomy with those from Europe and South America. Though monophyletic with the other , the isolates from Pakistan are distinguished by their high genetic variability and long branch lengths relative to the other isolates of , suggesting Pakistan as a possible ancestral area. Our results indicate that rice is severely attacked by a genetically diverse and aggressive , necessitating the development of appropriate control measures for its management in rice and other graminaceous crops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21307/jofnem-2020-123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015280PMC
January 2021

Gene Alterations of N6-Methyladenosine (mA) Regulators in Colorectal Cancer: A TCGA Database Study.

Biomed Res Int 2020 19;2020:8826456. Epub 2020 Dec 19.

Department of Environmental Health Sciences, Yale School of Public Health, 60 College Street, New Haven, CT 06520-8034, USA.

N6-methyladenosine (mA) plays an important role in many cancers. However, few studies have examined the role of m6A in colorectal CRC. To examine the effect of m6A on CRC, we studied the genome of 591 CRC cases from The Cancer Genome Atlas (TCGA). The relationship between the messenger RNA (mRNA) expression, copy number variation (CNVs), and mutations of m6A "Writers," "Readers," and "Erasers," prognosis, immune cell infiltration, and genetic mutations in CRC cases were analyzed. CNVs and mutations were found in thirteen m6A regulators. As expected, gain and amplification of m6A regulators increased the mRNA expression of these regulators, while deletion led to reduction in the mRNA expression. Moreover, CNVs and mutation of these regulators were significantly associated with APC, TP53, and microsatellite instability (MSI) status ( < 0.001, < 0.001, and = 0.029, respectively). CNVs of m6A regulators also correlated with inferred immune cell infiltration in CRC tissues, especially in colon tissues. Additionally, alterations of RBM15, YTHDF2, YTHDC1, YTHDC2, and METTL14 genes were related to the worse overall survival and disease-free survival (DFS) of CRC patients. Specifically, the deletion status of "Writers" was also correlated to the DFS of CRC patients ( = 0.02). Gene set enrichment analysis found that FTO was involved in mRNA 3' end processing, polyubiquitin binding, and RNA polymerase promoter elongation, while YTHDC1 was related to interferon-alpha and gamma response. In conclusion, a novel relationship was identified between CNVs and mutations of m6A regulators with prognosis and inferred immune function of CRC. These findings will improve the understanding of the relationship of m6A in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8826456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769650PMC
December 2020

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis.

Clin Transl Radiat Oncol 2021 Mar 16;27:15-23. Epub 2020 Dec 16.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

Purpose: Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown.

Methods: Patients with non-metastatic PDAC from 2006 to 2016 who received pre-operative MAC or MAC + RT before oncologic resection were identified in the National Cancer Database. Univariable and multivariable (MVA) associates with R0 resection were identified with logistic regression, and survival was analyzed secondarily with the Kaplan Meier method and Cox regression analysis.

Results: 4,599 patients were identified (MAC: 3,109, MAC + RT: 1,490). Compared to those receiving MAC, patients receiving MAC + RT were more likely to have cT3-4 disease (76% vs 64%, p < 0.001) and cN + disease (33% vs 29%, p = 0.010), but were less likely to have ypT3-4 disease (59% vs 74%, p < 0.001) and ypN + disease (32% vs 55%, p < 0.001) and more likely to have a pathologic complete response (5% vs 2%, p < 0.001) and R0 resection (86% vs 80%, p < 0.001). On MVA, MAC + RT (OR 1.58, 95% CI 1.33-1.89, p < 0.001), evaluation at an academic center (OR 1.33, 95% CI 1.14-1.56, p < 0.001), and female sex (OR 1.43, 95% CI 1.23-1.67, p < 0.001) were associated with higher odds of R0 resection, while cT3-4 disease (OR 0.81, 95% CI 0.68-0.96, p = 0.013) was associated with lower odds of R0 resection.

Conclusion: For patients with localized PDAC who receive pre-operative MAC, the addition of pre-operative RT was associated with improved rates of R0 resection and pathologic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctro.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772693PMC
March 2021

Treatment Selection and Survival Outcomes in Locally Advanced Proximal Gastric Cancer: A National Cancer Data Base Analysis.

Front Oncol 2020 25;10:537051. Epub 2020 Sep 25.

Department of Surgery, Yale School of Medicine, New Haven, CT, United States.

We aimed to assess long-term survival between locally advanced proximal gastric cancer (LAPGC) patients who underwent proximal gastrectomy (PG) and those who underwent total gastrectomy (TG) to evaluate the optimal extent of resection and adjuvant therapy. Patients diagnosed with locally advanced proximal gastric adenocarcinoma were selected from the National Cancer Data Base (2004-2015) in America. Survival analysis was performed via Kaplan-Meier and Cox proportional hazards models. A total of 4,381 eligible patients were identified, 1,243 underwent PG and 3,138 underwent TG. Patients in TG group had a poor prognosis (hazard ratio [HR] = 1.13, 95% confidence interval [CI]: 1.03-1.25) compared with those in PG group. Moreover, postoperative chemoradiation therapy was associated with improved overall survival compared to surgery alone (HR = 0.71, 95% CI: 0.53-0.97) in LAPGC patients who had PG, while preoperative chemotherapy (HR = 0.74, 95% CI: 0.59-0.92) was associated with improved survival among patients who had TG. Our study suggested that LAPGC patients underwent PG experienced better long-term outcomes than those underwent TG. It also suggested that multimodality treatment of LAPGC, including preoperative chemotherapy followed by TG or postoperative chemotherapy followed by PG, should be considered to achieve better long-term outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.537051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546198PMC
September 2020

Kynurenic acid underlies sex-specific immune responses to COVID-19.

medRxiv 2020 Sep 8. Epub 2020 Sep 8.

Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.09.06.20189159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491534PMC
September 2020

Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage.

Metabolites 2020 Jun 19;10(6). Epub 2020 Jun 19.

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06520, USA.

The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers ( = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon ( = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670-0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10060257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345993PMC
June 2020

Joint effect of pre-operative anemia and perioperative blood transfusion on outcomes of colon-cancer patients undergoing colectomy.

Gastroenterol Rep (Oxf) 2020 Apr 9;8(2):151-157. Epub 2019 Aug 9.

Department of Surgery, Yale School of Medicine, New Haven, CT, USA.

Background: Both pre-operative anemia and perioperative (intra- and/or post-operative) blood transfusion have been reported to increase post-operative complications in patients with colon cancer undergoing colectomy. However, their joint effect has not been investigated. The purpose of this study was to evaluate the joint effect of pre-operative anemia and perioperative blood transfusion on the post-operative outcome of colon-cancer patients after colectomy.

Methods: We identified patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database 2006-2016 who underwent colectomy for colon cancer. Multivariate logistic regression analysis was employed to assess the independent and joint effects of anemia and blood transfusion on patient outcomes.

Results: A total of 35,863 patients-18,936 (52.8%) with left-side colon cancer (LCC) and 16,927 (47.2%) with right-side colon cancer (RCC)-were identified. RCC patients were more likely to have mild anemia (62.7%) and severe anemia (2.9%) than LCC patients (40.2% mild anemia and 1.4% severe anemia). A total of 2,661 (7.4%) of all patients (1,079 [5.7%] with LCC and 1,582 [9.3%] with RCC) received a perioperative blood transfusion. Overall, the occurrence rates of complications were comparable between LCC and RCC patients (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.95-1.07; =0.750). There were significant joint effects of anemia and transfusion on complications and the 30-day death rate ( for interaction: 0.010). Patients without anemia who received a transfusion had a higher risk of any complications (LCC, OR=3.51; 95% CI=2.55-4.85; <0.001; RCC, OR=3.74; 95% CI=2.50-5.59; <0.001), minor complications (LCC, OR=2.54; 95% CI=1.63-3.97; <0.001; RCC, OR=2.27; 95% CI=1.24-4.15; =0.008), and major complications (LCC, OR=5.31; 95% CI=3.68-7.64; <0.001; RCC, OR=5.64; 95% CI=3.61-8.79; <0.001), and had an increased 30-day death rate (LCC, OR=6.97; 95% CI=3.07-15.80; <0.001; RCC, OR=4.91; 95% CI=1.88-12.85; =0.001) than patients without anemia who did not receive a transfusion.

Conclusions: Pre-operative anemia and perioperative transfusion are associated with an increased risk of post-operative complications and increased death rate in colon-cancer patients undergoing colectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gastro/goz033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136710PMC
April 2020

Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype.

Sci Rep 2020 03 17;10(1):4905. Epub 2020 Mar 17.

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA.

Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61851-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078199PMC
March 2020

Liver-first approach to stage IV colon cancer with synchronous isolated liver metastases.

J Gastrointest Oncol 2020 Feb;11(1):76-83

Section of Surgical Oncology, Yale School of Medicine, New Haven, CT, USA.

Background: The only possibility for cure in patients with colon adenocarcinoma (CAC) with isolated liver metastases (ILM) is resection of both primary and metastatic tumors. Little is known about the implication of the sequence in which a colectomy and hepatectomy are performed on outcomes. This study analyzes whether resection sequence impacts clinical outcomes.

Methods: The National Cancer Database was queried for CAC cases with hepatic metastases from 2010-2015 with exclusion of extrahepatic metastases. We compared patients treated with a liver-first approach (LFA) to those treated with a colectomy-first or simultaneous approach using Kaplan Meier and multivariable Cox proportional hazards analysis.

Results: In 21,788 CAC patients identified, the LFA was uncommon (2%), but was associated with higher rates of completion resection of remaining tumor (41% . 22%, P<0.001). Patients selected for LFA were younger, less comorbid, and more commonly received upfront chemotherapy (P<0.05). The LFA was associated with increased median survival [34 months, 95% CI (30.5-39.6 months) . 24 months, 95% CI (23.7-24.6 months), logrank P<0.001] and decreased risk of death [HR 0.783; 95% CI (0.67-0.89), P=0.001].

Conclusions: The LFA to CAC with synchronous ILM is uncommon but is associated with greater likelihood of receiving chemotherapy prior to surgery and increased survival in selected candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo.2020.01.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052756PMC
February 2020

Palliative care is underutilized and affects healthcare costs in ruptured abdominal aortic aneurysms.

Surgery 2020 08 3;168(2):234-236. Epub 2020 Mar 3.

Department of Surgery, Yale University, New Haven, CT; Department of Surgery, VA Connecticut Healthcare Systems, West Haven, CT. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2020.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748368PMC
August 2020

Exploring Microsatellite Instability (MSI) in Colorectal Cancer at Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST).

Ann Surg Oncol 2020 Apr 1;27(4):973-974. Epub 2019 Dec 1.

Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-019-08051-xDOI Listing
April 2020

Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer.

Transl Oncol 2020 Jan 21;13(1):42-56. Epub 2019 Nov 21.

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT USA. Electronic address:

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5' AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883319PMC
January 2020

Lymph Node Status: In Reply to Carr.

J Am Coll Surg 2019 11;229(5):516-517

New Haven, CT.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2019.07.007DOI Listing
November 2019

Hepatocellular carcinoma: Impact of academic setting and hospital volume on patient survival.

Surg Oncol 2019 Dec 12;31:111-118. Epub 2019 Oct 12.

Section of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. Electronic address:

Background And Objectives: To assess the impact of academic setting and hospital on overall survival in patient with hepatocellular carcinoma (HCC).

Methods: The 2004-2015 NCDB was queried for HCC. First line treatment was stratified as liver transplant, surgical resection, interventional oncology (IO) and chemotherapy. Hospital volume was stratified as high (ranking among top 10% in case numbers) and low volume. Overall survival was assessed via multivariable Cox regressions.

Results: 63,877 patients treated at 1261 hospital systems were included (transplant n = 10,596, surgical resection n = 11,132, IO n = 12,286, chemotherapy n = 29,863; academic centers n = 226, non-academic n = 1035). Younger African American patients with private insurance, high income and education were more likely treated at academic centers. US geographical discrepancies were evident, with highest academic center treatment rates in New England states (83.6%) and lowest in South Atlantic states (48.6%). Overall survival was superior for academic versus non-academic centers (HR = 0.89, 95% CI: 0.87-0.91, p < 0.001) and high versus low volume centers (HR = 0.79, 95% CI: 0.77-0.81, p < 0.001), after multivariable adjustment for potential confounders. These effects were evident among all HCC treatment modalities.

Conclusions: HCC treatment in academic centers shows distinct patterns according to patient demographics and US geography. Longest patient survival is observed in high-volume academic centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2019.10.009DOI Listing
December 2019

Digital Inference of Immune Microenvironment Reveals Low-Risk Subtype of Early Lung Adenocarcinoma.

Ann Thorac Surg 2020 02 27;109(2):343-349. Epub 2019 Sep 27.

Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.

Background: Classification of lung adenocarcinoma (LUAD) currently relies on the TNM pathological staging system, which cannot fully account for the variability in postsurgery overall survival (OS). Despite the advances in immunotherapy and increased appreciation of the involvement of cancer immune microenvironment (IME) in cancer progression, the contribution of IME to postsurgery LUAD prognosis is not well understood.

Methods: We digitally inferred the contribution of 22 immune cell types or activation states to the tumor IME using CIBERSORT (Celltype Identification By Estimating Relative Subsets Of RNA Transcripts) analysis in an exploratory metadataset of 581 patients with early-stage LUAD. Patients were arranged based on similarity in IME using k-means clustering. Relationship to postsurgical OS was tested in univariable and multivariable models using Kaplan-Meier analysis and Cox proportional hazards modeling, respectively. To confirm survival relationships, a support vector machine classifier was constructed from a comparison of low-risk and high-risk IME groups. The classifier was applied to a the Cancer Genome Atlas LUAD validation dataset of 394 patients.

Results: Patients with an inferred IME enriched in resting mast cells and depleted of macrophages represented a low-clinical-risk group in both exploratory and validation cohorts.

Conclusions: Variability in the digitally inferred composition of the tumor IME contributes to heterogeneity in postsurgical OS. Our data suggest that low inferred macrophage content and inferred resting activation state of intratumor mast cells are associated with improved clinical outcome. Computational inference can be used to define LUAD risk groups and help guide clinical decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2019.08.050DOI Listing
February 2020

APC mutational patterns in gastric adenocarcinoma are enriched for missense variants with associated decreased survival.

Genes Chromosomes Cancer 2019 Jul 28. Epub 2019 Jul 28.

Department of Surgery, Yale School of Medicine, New Haven, Connecticut.

Adenomatous polyposis coli (APC) mutations are causally associated with familial adenomatous polyposis (FAP) and are recurrent somatic events across numerous tumor types, including gastric adenocarcinoma. Severity of disease in FAP correlates with specific APC mutations, but the impact of given mutations on phenotype in gastric cancer is not well studied. Sequencing data from the Genomic Data Commons (GDC) demonstrate an APC mutational pattern in gastric cancer that differs dramatically from that seen in colon cancer. Exome sequencing data from APC-mutant colon and gastric adenocarcinomas in GDC was filtered for single nucleotide variants (SNVs) using MuTect2 Variant Aggregation and Masking pipeline, Somatic Aggregation Workflow. APC mutations were found in 57/441 gastric (12.9%) and 309/433 colon adenocarcinomas (71.4%). There was a significant difference in the proportion of stopgain, frameshift, and missense mutations between tumor types(P < .00001). Colon tumors were predominated by frameshift and stopgains, comprising 47.7% and 35.7%, respectively. In contrast, 47.1% of gastric mutations were missense. Gastric tumors harboring missense mutations showed decreased overall survival relative to other mutational subtypes(P = .008). In the gastric samples, 25.9% of frameshift and stopgain mutations are in the 3' portion of the gene, compared to 1.4% of colon samples. APC mutations demonstrate different distributions in gastric and colon adenocarcinoma, with a shift toward missense variants in gastric tumors and worse survival in gastric tumors harboring them. As different mutations confer variable degrees of protein dysfunction and resultant clinical manifestation, expanded investigation of specific mutational patterns will prove integral to future-risk stratification strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gcc.22792DOI Listing
July 2019

Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma.

J Immunother Cancer 2019 07 24;7(1):196. Epub 2019 Jul 24.

Section of Surgical Oncology, Yale School of Medicine, 20 Park Street, New Haven, CT, 06519, USA.

Background: Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.

Methods: We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.

Results: Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6% (P = 0.001). Five-year DSS after local therapy was 93% versus 31%, respectively (P = 0.046).

Conclusions: Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40425-019-0672-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657062PMC
July 2019

Comparison on Clinicopathological Features, Treatments and Prognosis between Proximal Gastric Cancer and Distal Gastric Cancer: A National Cancer Data Base Analysis.

J Cancer 2019 2;10(14):3145-3153. Epub 2019 Jun 2.

Department of Surgery, Yale School of Medicine, New Haven, CT 06520, United States.

: The aim of this study was to examine the differences in clinicopathological features, treatment strategies and prognosis between patients with proximal gastric cancer (PGC) and distal gastric cancer (DGC). : Patients with gastric adenocarcinoma were identified from the National Cancer Database during the years 2004-2015. Survival analysis was performed via Kaplan-Meier and Cox proportional hazards models. : A total of 97,060 patients were identified with gastric adenocarcinoma. DGC was associated with older age, more advanced tumor stage, and poorly differentiated tumors compared with PGC (all <0.01). In the multivariate analysis, patients with DGC had a worse prognosis compared with those with PGC. In early and locally advanced stage, the prognosis of DGC was better compared with PGC. In distant metastasis stage, the prognosis of DGC was worse compared with PGC. Compared with patients underwent gastrectomy who received adjuvant therapy (AT) in locally advanced stage, a survival benefit was seen for DGC patients who received neoadjuvant therapy (NAT) or NAT plus AT, whereas PGC patients with locally advanced disease did not share this result (>0.05). : PGC and DGC differed in their clinicopathologic characteristics and prognosis and heterogeneity may be due to differences in tumor biology. Tumor location should be taken into consideration when stratifying patients for optimal therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.30371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603385PMC
June 2019

The Role of Bowel Preparation in Open, Minimally Invasive, and Converted-to-Open Colectomy.

J Surg Res 2019 10 11;242:183-192. Epub 2019 May 11.

Department of Surgery, Yale School of Medicine, New Haven, Connecticut; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut. Electronic address:

Background: Bowel preparation before colectomy is considered an effective strategy to decrease postoperative complications. However, data regarding the effect of bowel preparation in patients undergoing minimally invasive colectomy are limited. The aim of this study was to investigate the role of different bowel preparation strategies in patients undergoing open, minimally invasive, and converted-to-open elective colectomies.

Methods: We identified 39,355 patients who underwent elective colectomy from the American College of Surgeons National Surgical Quality Improvement Program colectomy-targeted database (2012-2016). Multivariate logistic regression models were used to assess the impact of different bowel preparation strategies on postoperative complications and mortality in three subapproach groups: open (n = 12,141), minimally invasive (n = 23,057), and converted to open (n = 4157).

Results: Overall, a total of 10,066 (25.6%) patients received no preparation (NP), 11,646 (29.5%) mechanical bowel preparation (MBP) alone, 1664 (4.2%) antibiotic bowel preparation (ABP) alone, and 15,979 (40.6%) MBP + ABP. Compared with NP, MBP + ABP showed the strongest protective effects. MBP + ABP was associated with reduced risk of major complications (odds ratio [OR] = 0.60, 95% confidence interval [CI]: 0.55-0.66), infectious complications (OR = 0.50, 95% CI: 0.46-0.54), any complications (OR = 0.55, 95% CI: 0.51-0.60), 30-d mortality (OR = 0.68, 95% CI: 0.48-0.96), anastomotic leak (OR = 0.50, 95% CI: 0.43-0.58), and length of stay ≥ 4 d (OR = 0.64, 95% CI: 0.61-0.67) in overall population. These protective effects, except for 30-d mortality, were observed in open, minimally invasive, and converted-to-open groups. When the analysis was limited to robotic surgery only, MBP + ABP was only associated with reduced risk of major complications (OR = 0.61, 95% CI: 0.38-0.97) compared with NP. The protective effects remained similar over the study time period.

Conclusions: MBP + ABP is a preferred preoperative strategy in open, minimally invasive, and converted-to-open colectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2019.02.039DOI Listing
October 2019

Lungs nodule detection framework from computed tomography images using support vector machine.

Microsc Res Tech 2019 Aug 11;82(8):1256-1266. Epub 2019 Apr 11.

Department of EE, COMSATS University Islamabad, Wah Campus, Islamabad, Pakistan.

The emergence of cloud infrastructure has the potential to provide significant benefits in a variety of areas in the medical imaging field. The driving force behind the extensive use of cloud infrastructure for medical image processing is the exponential increase in the size of computed tomography (CT) and magnetic resonance imaging (MRI) data. The size of a single CT/MRI image has increased manifold since the inception of these imagery techniques. This demand for the introduction of effective and efficient frameworks for extracting relevant and most suitable information (features) from these sizeable images. As early detection of lungs cancer can significantly increase the chances of survival of a lung scanner patient, an effective and efficient nodule detection system can play a vital role. In this article, we have proposed a novel classification framework for lungs nodule classification with less false positive rates (FPRs), high accuracy, sensitivity rate, less computationally expensive and uses a small set of features while preserving edge and texture information. The proposed framework comprises multiple phases that include image contrast enhancement, segmentation, feature extraction, followed by an employment of these features for training and testing of a selected classifier. Image preprocessing and feature selection being the primary steps-playing their vital role in achieving improved classification accuracy. We have empirically tested the efficacy of our technique by utilizing the well-known Lungs Image Consortium Database dataset. The results prove that the technique is highly effective for reducing FPRs with an impressive sensitivity rate of 97.45%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jemt.23275DOI Listing
August 2019

Practice Patterns and Guideline Non-Adherence in Surgical Management of Appendiceal Carcinoid Tumors.

J Am Coll Surg 2019 06 19;228(6):839-851. Epub 2019 Mar 19.

Department of Surgery, Yale School of Medicine, New Haven, CT; Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT. Electronic address:

Background: Surgical management of appendiceal carcinoid tumors is heavily debated, despite National Comprehensive Cancer Network guidelines recommending aggressive resection of tumors >2 cm. We investigated national practice patterns and the predictors and impact of guideline non-adherence.

Study Design: The National Cancer Database was queried for cases of appendiceal carcinoids diagnosed from 2004 to 2015 treated with either appendectomy or hemicolectomy. Multivariable logistic regression, adjusted for demographic and clinical factors, identified associations with the procedure type among patients stratified by tumor size ≤2 cm and >2 cm. Cox Proportional Hazards then identified associations with overall survival among stratified patient groups.

Results: Of 3,198 cases of appendiceal carcinoids, 1,893 appendectomies and 1,305 hemicolectomies were identified. Contrary to National Comprehensive Cancer Network guidelines, 32.4% of tumors ≤2 cm were treated with hemicolectomy and 31.3% of tumors >2 cm were treated with definitive appendectomy. Hemicolectomy for small tumors was associated with age 65 years and older (odds ratio [OR] 2.4; 95% CI 1.7 to 3.3; reference group age 18 to 39 years), history of malignancy (OR 2.0; 95% CI 1.6 to 2.6), tumor size 1.1 to 2 cm (OR 2.8; 95% CI 2.3 to 3.4; reference group size ≤1 cm), and lymphovascular invasion (OR 2.2; 95% CI 1.6 to 3.2); appendectomy for large tumors was associated with age 65 years and older only (OR 2.2; 95% CI 1.1 to 4.2). Procedure type was not associated with survival for small or large tumors (hazard ratio 1.0; 95% CI 0.7 to 1.4 and hazard ratio 1.1; 95% CI 0.6 to 2.0, respectively).

Conclusions: Despite well-known size-based treatment guidelines for appendiceal carcinoids, one-third of patients in the US undergo hemicolectomy for small tumors and appendectomy for large tumors. Guideline non-adherence, however, is not associated with overall survival. Reasons for these practice patterns should be explored, and guidelines revisited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2019.02.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751559PMC
June 2019

Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database.

Ann Surg Oncol 2019 Jul 28;26(7):1993-2000. Epub 2019 Jan 28.

Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

Objective: The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC).

Methods: The 2004-2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models.

Results: Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16-1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01-1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04-1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65-0.82, p < 0.001).

Conclusions: ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-019-07175-4DOI Listing
July 2019

Review and current state of radiation therapy for locally advanced pancreatic adenocarcinoma.

J Gastrointest Oncol 2018 Dec;9(6):1027-1036

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.

Pancreatic cancer is characterized by a high rate of metastatic spread and overall poor prognosis. Yet 30% of patients have progressive local disease at the time of death, and local progression can cause significant morbidity. Approximately 30-40% of patients present with locally advanced pancreatic cancer (LAPC) that is not surgically resectable, and the optimal treatment for these patients continues to evolve. The role of radiation in the management of LAPC is an area of controversy, and the recent LAP07 randomized trial reported no survival benefit of radiation following gemcitabine plus or minus erlotinib. However, the efficacy of modern systemic regimens has improved since the design of the LAP07 study, and radiation therapy may be of greater benefit in the context of more effective systemic therapy. Advances in radiation delivery including the increasing use of stereotactic body radiation therapy (SBRT) have the potential to improve outcomes through dose escalation and better treatment tolerability. In addition, the combination of radiation therapy and immune therapy is an area of promising research. These advances suggest that radiation therapy will continue to play an integral role in the management of LAPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo.2018.03.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286948PMC
December 2018

Defining Early-Onset Colon and Rectal Cancers.

Front Oncol 2018 6;8:504. Epub 2018 Nov 6.

Section of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT, United States.

Colorectal cancer (CRC) incidence is rising in the young, yet the age of those affected is not clearly defined. In this study, we identify such cohorts and define clinicopathological features of early-onset colon and rectal cancers. The Surveillance, Epidemiology and End Results Program (SEER) database was queried to compare clinicopathological characteristics of colon and rectal cancers diagnosed during 1973-1995 with those diagnosed during 1995-2014. We identified 430,886 patients with colon and rectal cancers. From 1973-1995 to 1995-2014, colon cancer incidence increased in patients aged 20-44 years, while rectal cancer incidence increased in patients aged ≤54 years. The percent change of cancer incidence was greatest for rectal cancer with a 41.5% (95% confidence interval (CI): 37.4-45.8%) increase compared to a 9.8% (CI: 6.2-13.6%) increase in colon cancer. Colon cancer has increased in tumors located in ascending, sigmoid, and rectosigmoid locations. Adenocarcinoma histology has increased in both colon and rectal cancers ( < 0.01), but mucinous and signet ring cell subtypes have not increased ( = 0.13 and 0.08, respectively). Incidence increases were race-specific, with rectal cancer seeing similar rises in white (38.4%, CI: 33.8-43.1%) and black populations (38.0%, CI: 26.2-51.2%), while colon cancer as a whole saw a rise in white (11.5%, CI: 7.2-15.9%) but not black populations (-6.8%, CI: -14.6-1.9%). Our study underscores the existence of key differences between early-onset colon (20-44 years) and rectal cancers (≤54 years) and provides evidence-based inclusion criteria for future investigations. We recommend that future research of CRC in the young should avoid investigating these cases as a single entity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2018.00504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232522PMC
November 2018

Regional Differences in Palliative Care Utilization Among Geriatric Colorectal Cancer Patients Needing Emergent Surgery.

J Gastrointest Surg 2019 01 4;23(1):153-162. Epub 2018 Sep 4.

Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, PO Box 208062, New Haven, CT, 06520-8062, USA.

Background: The benefits of palliative care (PC) in critical illness are validated across a range of diseases, yet it remains underutilized in surgical patients. This study analyzed patient and hospital factors predictive of PC utilization for elderly patients with colorectal cancer (CRC) requiring emergent surgery.

Methods: The National Inpatient Sample was queried for patients aged ≥ 65 years admitted emergently with CRC from 2009 to 2014. Patients undergoing colectomy, enterectomy, or ostomy formation were included and stratified according to documentation of PC consultation during admission. Chi-squared testing identified unadjusted group differences, and multivariable logistic regression identified predictors of PC.

Results: Of 86,573 discharges meeting inclusion criteria, only 3598 (4.2%) had PC consultation. Colectomy (86.6%) and ostomy formation (30.4%) accounted for the operative majority. PC frequency increased over time (2.9% in 2009 to 6.2% in 2014, P < 0.001) and was nearly twice as likely to occur in the West compared with the Northeast (5.7 vs. 3.3%, P < 0.001) and in not-for-profit compared with proprietary hospitals (4.5 vs. 2.3%, P < 0.001). PC patients were more likely to have metastases (60.1 vs. 39.9%, P < 0.001) and die during admission (41.5 vs. 6.4%, P < 0.001). On multivariable logistic regression, PC predictors (P < 0.05) included region outside the Northeast, increasing age, more recent year, and metastatic disease.

Conclusions: In the USA, PC consultation for geriatric patients with surgically managed complicated CRC is low. Regional variation appears to play an important role. With mounting evidence that PC improves quality of life and outcomes, understanding the barriers associated with its provision to surgical patients is paramount.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-018-3929-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751557PMC
January 2019

Clinical impact of underutilization of adjuvant therapy in node positive gastric adenocarcinoma.

J Gastrointest Oncol 2018 Jun;9(3):517-526

Department of Surgery, Section of Surgical Oncology, Yale University School of Medicine, New Haven, CT, USA.

Background: Adjuvant therapy for gastric adenocarcinoma has shown a survival advantage, though it may be underutilized. The purpose of this study is to examine how infrequently adjuvant therapy is administered with curative intent gastrectomy for node positive gastric cancer and the long-term effects to patients.

Methods: The National Cancer Database was queried from 2006-2013 for patients with node positive gastric adenocarcinoma undergoing a potentially curative gastrectomy. Overall survival was compared between patients who received adjuvant chemotherapy or chemoradiation and those who did not.

Results: Of 2,565 patients, 793 (30.9%) patients did not receive any adjuvant chemotherapy or radiation therapy, while 147 (5.7%) received peri-operative chemotherapy and 723 (28.2%) received post-operative chemoradiation. From 2006-2013, the percentage of patients receiving peri-operative chemotherapy rose from 1.1% to 9.9%, while those receiving post-operative chemoradiation decreased from 39.7% to 21.6%. The adjusted restricted mean survival time over 5 years for no adjuvant therapy was 27.7 months, peri-operative chemotherapy was 39.6 months, and post-operative chemoradiation was 37.7 months (P<0.0001).

Conclusions: Approximately one third of patients treated for node positive gastric cancer undergo surgical resection without adjuvant therapy. This is associated with poorer survival, highlighting the need for improvement in multimodality care and cancer outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo.2018.03.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006033PMC
June 2018

NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018.

J Natl Compr Canc Netw 2018 06;16(6):693-702

The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2018.0056DOI Listing
June 2018

Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum.

J Gastrointest Oncol 2018 Apr;9(2):231-240

Department of Surgery, Section of Surgical Oncology, Yale University School of Medicine, New Haven, CT, USA.

Background: Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care.

Methods: The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared.

Results: A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% 34.0% 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032).

Conclusions: Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo.2017.11.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934147PMC
April 2018