Colorectal Cancer and Nutrition

Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer

Colorectal Cancer and Nutrition

Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer

Synthesis, spectral, crystallographic, and computational investigation of a novel molecular hybrid 3-(1-((benzoyloxy)imino)ethyl)-2H-chromen-2-ones

Synthesis of 3-(1-((benzoyloxy)imino)ethyl)-2H-chromen-2-ones (1-5) was accomplished and it was characterized experimentally using various analytical techniques. Computational studies have been carried out for all compounds 1-5 using B3LYP method with 6-311++G(d,p) basis set. The optimized structural features viz. bond lengths, bond angles, and dihedral angles are compared with their single-crystal X-ray diffraction results of compound 1 (Crystal data for C18H13NO4 (M = 307.29 g/mol): Monoclinic, space group P21/c (no. 14), a = 11.399(5) Å, b = 5.876(5) Å, c = 21.859(5) Å, β = 91.060(5)°, V = 1463.9(14) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.100 mm-1, Dcalc = 1.394 g/cm3, 13555 reflections measured (3.58° ≤ 2Θ ≤ 56.98°), 3669 unique (Rint = 0.0235) which were used in all calculations. The final R1 was 0.0444 (>2sigma(I)) and wR2 was 0.1506 (all data)), which are in good conformity with each other. Normal modes of vibrational frequencies of compounds 1-5 acquired from density-functional theory (DFT) method coincided with the experimental ones. The 1H and 13C chemical shifts of compounds 1-5 have been calculated by GIAO method and the results have been compared with the experimental ones. The first-order hyperpolarizability and their related properties of the novel molecules 1-5 are calculated computationally. The other parameters like natural bond orbital, zero-point vibrational energy, EHOMO, ELUMO, heat capacity and entropy have also been discussed

Desperate times, desperate measures: successful use of chemotherapy in treatment of haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis

We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement

COVID-19 and Cancer: Lessons Learnt from a Michigan Hotspot

Background: Outcomes with coronavirus disease 2019 (COVID-19) have been worse in those with comorbidities and amongst minorities. In our study, we describe outcomes amongst cancer patients in Detroit, a major COVID-19 hotspot with a predominant inner-city population. Methods: We retrospectively analyzed 85 patients with active invasive cancers who were infected with COVID-19. The primary outcome was death or transition to hospice. Results: The majority were males (55.3%, n = 47), ≤70 years old (58.5%, n = 50), and African Americans (65.5%, n = 55). The most common primary site was prostate (18.8%, n = 16). Inpatient admission was documented in 85.5% (n = 73), ICU admission in 35.3% (n = 30), and primary outcome in 43.8% (n = 32) of hospitalized patients. On a multivariate analysis, factors associated with increased odds of a primary outcome included an age of \u3e70 years versus ≤70 years (OR 4.7, p = 0.012) and of male gender (OR 4.8, p = 0.008). Recent cancer-directed therapy was administered in 66.7% (n = 20) of ICU admissions versus 39.5% (n = 17) of general floor admissions (Chi-square p-value of 0.023). Conclusions: High rates of mortality/transition to hospice and ICU utilization were noted amongst our patients with active invasive cancer, following a COVID-19 infection. Men and those of \u3e70 years of age had a greater than four-fold increase in odds of death or transition to hospice

Disparities in Utilization of Autologous Stem Cell Transplantation as Consolidative Therapy for Multiple Myeloma: A Single Institution Retrospective Review

BACKGROUND: Most guidelines recommend induction therapy followed by autologous hematopoietic cell transplantation. A Surveillance, Epidemiology, and End Results-Medicare database analysis from 2000 to 2011 noted a lower use of HCT and bortezomib among Black patients, despite adjusting for care barriers, and this practice was associated with a poorer outcome. The goal of this study was to evaluate patterns of acceptance of HCT as consolidative therapy for MM. METHODS: Cox proportional hazards model was used to investigate the association between the survival time of the patients (overall survival) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. A total of 194 patients with a confirmed diagnosis of MM who were referred for HCT between January 1, 2009, and June 30, 2019, were included in this study. Patients who received autologous stem cell transplant for relapsed MM were excluded. RESULTS: We found that income category was not significantly associated with overall survival, time to transplant or transplant-/relapse-related mortality. High-risk cytogenetic was significantly associated with shorter overall survival, higher transplant-related mortality and relapse-related mortality (P \u3c .002). The use of aggressive induction choices was associated with poorer transplant outcomes (P = .02). Time to transplant tended to be shorter in African American compared with other ethnic groups (P = .07). CONCLUSION: There was no significant difference in the use rate of the HCT between Caucasians and AA patients with MM. Further comparative studies of MM induction therapy and access to clinical trials in African Americans and other racial minorities are warranted

Molecular characteristics of pancreatic neuroendocrine tumors, do they correlate with metastases?

Background: Pancreatic neuroendocrine tumors (PNET) have an unpredictable biological behavior that cannot be reliably predicted by histological and clinical manifestations. We performed next generation sequencing (NGS) on PNET to understand the molecular pathogenesis and to identify potential biomarkers correlating with metastases and survival. Design: Hybrid capture-based comprehensive genomic profiling was performed on both primary and metastatic PNET from 28 patients. Metastatic sites were grouped as lymph nodes and distant metastases (consisted of liver followed by bone). NGS was performed on genomic DNA & RNA isolated from formalin-fixed paraffin embedded tissue using the whole exome NGS assay covering 20,000 genes. Average number of DNA reads was 52 million at 3:1 somatic to germline. All variants were detected with \u3e99% confidence based on allele frequency and amplicon coverage, with an average sequencing depth of coverage \u3e500x and an analytical sensitivity of 5%. Tumor mutation burden and MSI status were compared using the two-sample t-test between tumor types. Frequency of mutations in each gene was compared between tumor types using the Fisher\u27s exact test. To account for multiple comparisons, the False Discovery Rate was estimated using Benjamini-Hochberg procedure. R package maftools was used to summarize and visualize the findings. Results: Mutation burden was higher in primary tumors with metastases versus primary tumors without metastases (p=0.034) while no significance was found in MSI status between these two groups. Among the 20 mutated genes, MUC4 and MEN1 were the most frequently mutated genes in both primary and metastatic tumors (fig1&2). At a p-value threshold of 0.2, two distant metastatic tumors had mutation on PCNX3 gene, while none were found in lymph node metastases (p=0.057). In addition, more mutations on TGFBR1 in distant metastases compared to lymph node metastases (p=0.154). We also found that three primary tumors with metastases had mutations on E2F4, HRNR, LRP1B genes while none were found in primary tumors with no metastases (p=0.2). (Figure presented) Conclusions: Decoding the complexity and unpredictable nature of PNET has been perplexing and the subject of many several research projects. The current project, the first ever done on the subject, with an attempt to distinguish the metastatic vs non-metastatic tumors try to underlie the difference of molecular signature between the two. Further studies are needed to consolidate the findings and bring them to clinical practice

Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery