Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database.

BACKGROUND: Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. METHODS: Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. RESULTS: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers. CONCLUSION: Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

Extramedullary Hematopoiesis in Mismatch Repair Deficient Colon Cancer Patient on Adjuvant Chemotherapy.

A 59-year-old male presented with a two-month history of abdominal pain and was found to have an obstructing cecal mass. Colonoscopy and biopsy confirmed invasive adenocarcinoma. Immunohistochemical analyses for mismatch repair (MMR) proteins revealed the loss of MLH1 as well as PMS2 in cancerous nuclei, which makes the tumor MMR deficient. Negative germline testing for MMR proteins ruled out the Lynch syndrome. After negative staging computerized tomography scan for distant metastases, he underwent ileocolectomy with ileotransverse colonic anastomosis. Final pathological analysis revealed poorly differentiated adenocarcinoma with signet ring features, negative margins, and 3/22 lymph nodes positive, classified as stage IIIB (T4aN1bM0). Adjuvant chemotherapy with modified FOLFOX (leucovorin calcium/folinic acid, fluorouracil, and oxaliplatin) was started without the use of any growth factor support. After cycle 9 of 12, he developed mild transaminitis, carcinoembryonic antigen elevation, and interval development of two heterogeneously enhancing hepatic lesions. Biopsy of both of these lesions revealed extramedullary hematopoiesis (EMH), with no evidence of metastatic disease. He completed adjuvant chemotherapy without complication, and these liver lesions have decreased in size during the follow-up period of almost two years thus far. EMH is extremely rare in patients with colon cancer. Contributing factors include therapy-specific (growth factor support), bone marrow suppression secondary to chemotherapy and radiation therapy, and tumor-specific factors (cytokine and growth factors released by the tumor). To the best of our knowledge, this is the first case report of EMH in an MMR deficient colon cancer patient on adjuvant FOLFOX. MMR-deficient tumors show signs of a high degree of infiltration with CD8+ cytotoxic T lymphocytes as well as helper T cells, leading to increased production of cytokines, such as interferon-γ. This could be a potential etiology behind EMH in our patient who was MMR deficient. The role of the MMR-deficient state in the development of EMH should be explored further.

HPV-16-associated lymphoepithelial-like carcinoma mimicking rectal tonsil.

Lymphoepithelial-like carcinoma is a rare malignancy characterized by lack of cellular differentiation and associated nonneoplastic lymphoplasmacytic cell infiltrate that is rarely seen in the colon. Although many cases are associated with EBV infection, HPV may be present in LELC arising in sites known for HPV-driven malignancies, like the anogenital region. We report a case of lymphoepithelial-like carcinoma mimicking a rectal tonsil in a 51-year-old female. Attentive evaluation must be taken to identify this tumor in locations where prominent lymphoid stroma is an expected finding.

Two Cases of Rare Pancreatic Malignancies.

Background: Pancreatic adenocarcinoma remains one of the most lethal malignancies with little treatment advancements. Other less common pancreatic cancer histologies have different outcomes and disease course. In this article, we report two cases of rare pancreatic tumors. Presentation: The first case is a 59-year old, who was undergoing surveillance of a known pancreatic cyst, which eventually enlarged. The mass was resected and pathology revealed undifferentiated carcinoma with osteoclast-like giant cells. The patient did not receive any adjuvant therapy and has had no recurrence. The second case is of a 60-year-old patient who presented with signs and symptoms of pancreatic insufficiency and was found to have clear cell adenocarcinoma of the pancreas. She received neoadjuvant chemoradiotherapy followed by surgical resection without complications. Conclusion: Our article presents these rare malignancies, which had outcomes that are more encouraging than typical adenocarcinomas. Genomic sequencing can provide more insight into these tumors and potentially provide targets for therapy.

Immunotherapy for Colorectal Cancer: A Review of Current and Novel Therapeutic Approaches.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States. Although immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, the benefit in CRC has thus far been limited to patients with microsatellite instability high (MSI-H):DNA mismatch repair-deficient (dMMR) tumors. Recent studies in the refractory CRC setting have led to US Food and Drug Administration approvals for pembrolizumab as well as nivolumab (with or without ipilimumab) for tumors harboring an MSI-H:dMMR molecular profile. Several randomized controlled trials are underway to move immunotherapy into the frontline for metastatic cancer (with or without chemotherapy) and the adjuvant setting. Awareness of these studies is critical given the relatively low incidence (approximately 3%-5%) of MSI-H:dMMR in advanced or metastatic CRC to support study completion, because the results could be potentially practice changing. The real challenge in this disease is related to demonstrating the benefit of immunotherapy for the vast majority of patients with CRC not harboring MSI-H:dMMR. Given the rapid pace of scientific changes, this article provides a narrative review regarding the current landscape of immunotherapy for CRC. Particular attention is paid to the currently available data that inform today's clinical practice along with upcoming randomized controlled trials that may soon dramatically change the treatment landscape for CRC.

5-FU induced cardiotoxicity: case series and review of the literature.

BACKGROUND: 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy used for a variety of solid tumors. It has the potential to cause a wide spectrum of cardiotoxicity, ranging from asymptomatic electrocardiographic changes to cardiomyopathy and subsequent cardiac failure. Main body of the abstract: We present two descriptive cases of new-onset severe cardiomyopathy induced by 5-FU followed by a review of the literature. CONCLUSION: Our case series emphasizes the importance of early recognition of this rare complication and prompt cessation of 5-FU, as cardiac dysfunction in this context is potentially reversible.

Active Smoking Is Associated With Worse Prognosis in Metastatic Renal Cell Carcinoma Patients Treated With Targeted Therapies.

BACKGROUND: Smoking increases the risk of developing renal cell carcinoma (RCC) but the effect of tobacco consumption on survival outcome of patients with metastatic RCC (mRCC) treated with targeted therapies has not been well characterized. PATIENTS AND METHODS: The primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). Patients with mRCC were categorized as current, former, and nonsmokers at the time of starting targeted therapy. Smoking data from 1980 patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium (IMDC) from 12 international cancer centers. RESULTS: Although former and nonsmokers had comparable OS times (23.8 vs. 23.4 months; P = .898), current smokers had significantly shorter OS (16.1 months; P < .001) than nonsmokers. Current but not former smoking status was an independent poor prognosis factor (hazard ratio [HR], 1.3; P = .002) when adjusted for the IMDC risk criteria. Each pack-year increased the risk of death by 1% (HR, 1.01; P = .036). The duration of first-line therapy response was not different and was 7.7 months versus 7.5 months versus 6.4 months in never, former (P = .609), and current smokers (P = .839), respectively. CONCLUSION: Active smoking is associated with diminished OS in mRCC patients treated with targeted therapy agents. However, patients who quit smoking returned to a similar risk of death from RCC compared with patients who never smoked. Smoking cessation should be a counseling priority among mRCC patients receiving targeted agents and smoking should be considered as a confounding factor in major clinical trials.

Extragastrointestinal stromal tumors of the pelvic cavity and the vagina: Two case reports and review of the literature.

Gastrointestinal stromal tumors (GISTs) are rare tumors of gastrointestinal (GI) tract with mesenchymal cell origin. Extragastrointestinal stromal tumors (EGISTs) are unusual tumors that exhibit the same immunohistochemical and genetic abnormalities as GISTs and most commonly affect the omentum and mesentery. EGISTs of the pelvis and the female reproductive system are exceedingly rare and a frequent diagnostic pitfall. In this report, we present two cases of EGISTs along with a review of the literature.

Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management.

Colorectal carcinoma is the second leading cause of cancer-related deaths in the United States, with rectal cancer accounting for approximately one-third of newly diagnosed cases, thus representing a major socioeconomic health burden. Although minimally invasive procedures (ie, transanal excision) may be appropriate for a subset of patients with small, superficially invasive tumors, a more comprehensive trimodality approach with neoadjuvant chemoradiotherapy, total mesorectal excision, and systemic chemotherapy is recommended for medically operable patients with nonmetastatic, locally advanced rectal cancer (LARC). Although such multimodality therapy has markedly reduced local recurrence rates, there remains an estimated 5-year distant relapse rate of 35%, representing the leading cause of death in this population. This review critically assesses the literature regarding neoadjuvant therapy for LARC, as well as the available evidence to support selective exclusion of individual modalities from the contemporary therapeutic paradigm, including controversies of nonoperative management, selective radiation sparing, and neoadjuvant systemic therapy. Through the review of existing data and the anticipated results of ongoing clinical trials, we outline the pragmatic opportunities for future investigation into questions of efficacy, safety, and ultimate improvements to the current status quo.

Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review.

INTRODUCTION: Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent. DISCUSSION: This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection. CONCLUSION: Identification and optimization of these clinical factors could make a meaningful impact on the patient's quality of life.

The Multidisciplinary Approach to Localized Pancreatic Adenocarcinoma.

OPINION STATEMENT: Pancreatic adenocarcinoma 2030 (PCa) is predicted to be the second leading cause of cancer death in USA by 2030. To date, attempts at early detection have been unsuccessful. Therapies for resectable PCa include surgery followed by adjuvant chemotherapy with or without radiotherapy. Unfortunately, most patients with PCa present with advanced disease and thus only 20% of patients are potentially resectable upon presentation. Improved surgical techniques along with adjuvant combination chemotherapy have improved outcomes for patients with resectable disease. The optimal treatment approach for borderline resectable and locally advanced unresectable PCa has not yet been defined. Despite significant advances in the palliative treatment of PCa, long-term survival of early stage disease continues to be sobering. The key to improving outcomes for this largely fatal disease is to identify multidisciplinary therapeutic interventions including surgical, medical, and radiation techniques tailored to the patient and their disease characteristics. The neoadjuvant approach provides an in vivo platform to test novel treatment options to help us understand tumor biology and surrounding microenvironment, which may ultimately help us achieve the goal of improvement in long-term survival. While the neoadjuvant approach remains popular as a way to optimally select patients that might benefit most from surgery, randomized trials utilizing adjuvant and neoadjuvant novel therapies hold the key to truly personalizing the ideal treatment strategy for localized PCa.

Axitinib for the treatment of metastatic renal cell carcinoma.

Renal cell carcinoma is a cancer that results from a genetic inactivation of the VHL tumor suppressor gene leading to an upregulation of VEGF. Targeted therapies against VEGF receptors have piqued substantial interest among clinicians and researchers, and these drugs are now the standard of care in the treatment of advanced renal cell carcinoma. One of these VEGF receptor inhibitors, axitinib, has been shown to be a superior second-line therapy when compared with sorafenib. Although axitinib has clinical activity and a manageable safety profile in patients with treatment-naive metastatic renal cell carcinoma, utility in the front-line setting is area of ongoing investigation. Another area of ongoing research is dose titration of axitinib to achieve the maximum clinical benefit. Interestingly, the axitinib-related side effect of hypertension has shown to be associated with more favorable clinical outcomes. This article describes the development of axitinib and discusses the current indications for clinical use in the management of metastatic renal cell carcinoma.

Emerging therapeutic approaches in renal cell carcinoma.

In the past decade, targeted therapy with VEGF and mTOR inhibition has significantly improved the outcome of renal cell carcinoma. However, the management of metastatic renal cell carcinoma still remains challenging as most patients eventually progress on targeted therapy, and long-term survivors are still relatively uncommon. There has recently been a resurgence of interest in cancer immunotherapy with the development of checkpoint inhibitors. Here we discuss the best methods to optimize the current standard of care with targeted therapy, and describe select emerging targeted therapies and immunotherapies with anti programmed death-1 pathway inhibitors in the management of metastatic renal cell carcinoma.

High-dose cytosine arabinoside-induced symptomatic bradycardia.

Cardiac complications of high-dose cytosine arabinoside (HiDAC), although rare, predominantly include pericarditis, pericardial effusion and cardiomyopathy (with concurrent use of cyclophosphamide). Clinically significant arrhythmias associated with HiDAC, although reported in the literature, are rare. The following case report has for the first time used the Naranjo Scale to document a high-probability association (definite adverse drug reaction) of cytarabine with symptomatic sinus bradycardia.

Synchronous multifocal osteogenic sarcoma on multimodality imaging including bone scintigraphy.

Multifocal osteosarcoma is diagnosed when there are two or more lesions in the skeleton without presence of pulmonary metastases. It is further classified as synchronous type when the patient is demonstrated to have more than one lesion simultaneously at presentation and is known as Synchronous Multifocal Osteogenicsarcoma (MOGS). We report a case of synchronous MOGS showing its multimodality imaging findings including nuclear scan findings with pathological correlation.

Disseminated fusariosis occurring in two patients despite posaconazole prophylaxis.

Posaconazole is widely used for prophylaxis against invasive fungal infections in patients undergoing myeloablative therapy. Disseminated fusariosis is a serious invasive mold infection in such patients. Preclinical and clinical studies indicate activity of posaconazole against Fusarium. We describe two cases of disseminated fusariosis that occurred despite posaconazole prophylaxis.