Chemotherapy Recipients Research Articles

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Body weight and composition changes, primary tumor side, and resection as survival predictors in metastatic colorectal cancer.

850 Background: Common symptoms of metastatic colorectal cancer (mCRC) are sarcopenia and weight loss. We investigated whether weight loss, sarcopenia and primary tumor resection can predict overall survival among patients (pts) with mCRC Methods: Consecutive pts newly diagnosed with mCRC in a community hospital between 2012-2014 we reviewed. We gathered initial and 6-month follow up data on weight, standardized muscle mass measure (estimated psoas muscle area/m2 height, sEPA) and subcutaneous fat (SQ). Results: There were 109 pts (age 66.9±14.5, range 37-93 years). Chemotherapy recipients were younger (n = 59, 61.2±13.3 years) and survived longer (22.3 versus 5.3 months, p < 0.001) as compared to best supportive care patients (n = 50, 73.6±13.0 years, p < 0.001). There were no baseline and 6-month differences between pts with resected versus in situ primary tumor in age (p = 0.074), baseline weight (p = 0.728) or percent weight loss (p = 0.404), albumin (p = 0.322), hemoglobin (p = 0.301), creatinine (p = 0.791), initial standardized EPA (p = 0.866), percent of sEPA loss (p = 0.952), and percent subcutaneous thickness loss (p = 0.477). Cohort was further dichotomized by median anthropometric changes at 6 months: -7.1% for weight loss, -6.2% sEPA, -3.3% SQ fat. Cox proportional hazard models demonstrated that anthropometric measures and receipt of systemic chemotherapy were the strongest predictors of survival with their predictive strength surpassing traditional predictors as age, tumor sidedness, primary tumor resection, initial BMI and serum albumin level. Conclusions: Weight loss and anthropometric changes are strongly associated with shorter survival. Prognostic characteristics of loss of weight, muscle and fat should be investigated further using more robust datasets. [Table: see text]

The course of infection caused by Encephalitozoon cuniculi genotype III in immunocompetent and immunodeficient mice

Encephalitozoon cuniculi is probably the most common microsporidia which infects a wide range of vertebrates, including human. So far, four genotypes of this parasite have been identified based on the rRNA internal transcribed spacer variations.The course of infection caused by E. cuniculi III had very massive onset in immunocompetent host characterized by the presence of this parasite in all organs and tissues within one week after peroral infection. Encephalitozoonosis caused by E. cuniculi III had very progressive spreading into all organs within first week post inoculation in immunocompromised SCID mice and led to the death of the host. The experimental treatment with albendazole of immunocompetent BALB/c mice infected with E. cuniculi III have shown very weak effect.Our findings clearly showed that the different course of infection and response to treatment depends not only on the immunological status of the host, but also on the genotype of microsporidia. It could be very important especially for individuals under chemotherapy and transplant recipients of organs originating from infected donors.

Rising Bilateral Mastectomy Rates Among Neoadjuvant Chemotherapy Recipients in California From 1998 to 2012.

To study the impact of rising bilateral mastectomy rates among neoadjuvant chemotherapy (NAC) recipients in California. NAC for operable breast cancer (BC) can downstage disease and facilitate breast conservation. We assessed trends in NAC use and surgical procedures in California from January 1, 1998 to December 31, 2012 using statewide population-based cancer registry data. A total of 236,797 females diagnosed with stage I-III BC were studied. Information regarding NAC, adjuvant chemotherapy (aCT), breast conserving surgery (BCS), bilateral mastectomy (BLM), and unilateral mastectomy (ULM) was abstracted from the medical records. Multivariable polytomous logistic regression was used to estimate odds ratios (OR) of receiving NAC and of type of surgery after NAC. Approximately, 40.1% (94,980) of patients received chemotherapy: 87% (82,588) aCT and 13.0% (12,392) NAC. NAC use more than doubled over time and increased with stage (Stage I, 0.7%; Stage III, 29.9%). Multivariable predictors of NAC treatment were stage (III), younger age (<40 yrs), Black or Hispanic race/ethnicity versus non-Hispanic White (OR 1.10, 95% confidence interval (CI) 1.05-1.16), and care at a National Cancer Institute (NCI)-designated center (OR 1.70, CI 1.58-1.82). Most NAC recipients (68.4%) had mastectomies, and 14.3% of them underwent BLM. In contrast, 47.9% aCT patients had mastectomies with 7.3% BLM. The only independent predictor of BCS after NAC was care at a NCI-designated center (OR 1.28, CI 1.10-1.49), and of BLM, age <40 years versus 50 to 64 years (OR 2.59, CI 2.21-3.03), or residence in the highest socioeconomic neighborhood quintile versus lowest (OR 2.10, CI 1.67-2.64). NAC use remains low. Predictors of surgery type after NAC were sociodemographic rather than clinical, raising concern for disparities in care access.

Evaluating the association between adjuvant chemotherapy and function-related adverse events among older patients with early stage breast cancer.

The incidence of treatment-related toxicity for adjuvant chemotherapy in breast cancer is well documented in clinical trials. However, the effect of chemotherapy on functional outcomes in older patients is less well known. We identified a cohort of older women diagnosed with early stage breast cancer to examine the association between exposure to chemotherapy and a claims-based measure of function-related adverse events (FAE). Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset, we identified women aged ≥66 diagnosed with stage I or II breast cancer from 2004 to 2011. FAE were defined as one or more claims suggestive of functional impairment within 24months following chemotherapy including claims for durable medical equipment and skilled care. Women who did not receive chemotherapy were weighted to reflect the covariate distribution of chemotherapy recipients using propensity score weighting for age, stage, baseline healthcare utilization, and comorbidities. The cohort included 44,626 patients, 6892 (15%) received chemotherapy. 19% of the population experienced ≥1 FAE. After propensity weighting, chemotherapy was associated with a small increased risk of FAEs (HR 1.12, 95% confidence interval: 1.04, 1.20). Results were similar in patients 75years and older versus younger patients. In the chemotherapy group, the highest risk of FAE occurred in the first 3months, but persisted through follow-up. Exposure to chemotherapy was associated with a small increased risk of FAE which did not vary by age. These data can be used to inform treatment decision making for older patients with breast cancer who are eligible for adjuvant chemotherapy.

Serum metabolism during breast cancer treatment.

e23043 Serum metabolism during breast cancer treatment Background: Breast cancer treatment may include surgery, systemic therapy and radiation, often involving side-effects. Many patients experience weight gain during treatment, which is associated with decreased survival rates1. The purpose of this study was to describe serum metabolic alterations in breast cancer patients undergoing treatment, and relate these alterations to weight gain during treatment. Methods: This pilot study includes 60 breast cancer patients, aged 35-75 years, with histologically verified stage I/II disease. All patients underwent tumor surgery, and were treated according to national guidelines. Samples were collected before and 6 months after surgery, and analyzed by MR spectroscopy (MRS) and mass spectrometry (MS). 170 metabolites and 105 lipoprotein subfractions were quantified by combined MRS and MS analyses. Results: Multilevel PLS-DA showed significant alterations in serum metabolite profiles post-treatment, both in patients receiving (n = 35) and not receiving (n = 25) chemotherapy (classification accuracy: 86.7% and 77.0%, resp., p &lt; 0.001). Lipoprotein profiles were also significantly altered in both groups (p &lt; 0.001). Chemotherapy recipients had decreased levels of citrate, ornithine, and methionine after treatment, while non-recipients had increased levels of glutamate, alanine, proline and two biogenic amines, and decreased levels of acylcarnitines. 17/52 patients (32.7%) gained weight (≥ 1.5 kg) during treatment. Weight gain was predicted from pre-treatment samples with accuracy 67.0% (p = 0.020). Weight gain patients had lower levels of three acylcarnitines and 20 phosphocholines, and higher levels of lysine and isoleucine, suggesting aberrant lipid and amino acid metabolism. Weight gain was also reflected in the post-treatment samples (accuracy 66.8%, p = 0.015), with weight gain patients having higher levels of five acylcarnitines, and lower levels of glycine, isoleucine and valine. Conclusions: This study indicates that treatment induces changes in serum metabolite levels. Patients gaining weight had significantly different metabolite profiles than those not gaining weight both before and after treatment. 1. Chan et al, Ann Oncol 25: 1901-14, 2014.

Advanced Primary Epithelial Ovarian and Peritoneal Carcinoma-Does Diagnostic Accuracy of Preoperative CT Scan for Detection of Peritoneal Metastatic Sites Reflect into Prediction of Suboptimal Debulking? A Prospective Study.

Ovarian cancer is the seventh most common cancer in females worldwide. Optimal debulking is the standard treatment but possible only in 30-85% of advanced stages. Knowing exactly the disease extent preoperatively may predict suboptimal debulking. We analyzed diagnostic accuracy of preoperative CT scan in disease mapping and prediction of suboptimal debulking in a prospective observational study from March 2013 to May 2015 in a tertiary hospital. Adults below the age of 75years with ECOG PS-0, 1, 2, clinically/radiologically newly diagnosed stage IIIc epithelial ovarian (EOC), and primary peritoneal carcinoma (PPC) were included. Neoadjuvant chemotherapy recipients were excluded. Preoperative multidetector CT (MDCT) scan showing deposits at 19 predetermined abdominopelvic sites were compared with the same sites seen at laparotomy and corresponding accuracies of CT scan calculated. Primary debulking surgery was done to achieve debulking to nil or less than 1-cm residual disease. Stepwise logistic regression models were used to determine the frequent suboptimal debulking sites and the predictive performance of the clinical and CT scan findings. A total of 36 patients were enrolled. The optimal debulking rate was 50%. The CT scan could detect the disease-bearing sites with overall sensitivity of 68.29%, specificity of 89%, accuracy of 78.07%, and positive and negative predictive values of 99 and 50.1%, respectively. Upon multivariate analysis, bowel mesentery (p 0.011) and omental extension (p 0.025) were associated with suboptimal debulking. CT scan accuracy at these sites (predictive performance) was 86.1%. We identified small bowel mesentery and omental extension (to spleen/stomach/colon) as sites associated with suboptimal debulking. MDCT accurately depicts peritoneal metastases, although sensitivity is reduced in certain areas of significance for optimal debulking. Further validation with more number of patients is warranted.

B cell and antibody responses in mice induced by a putative cell surface peptidase of Pneumocystis murina protect against experimental infection

RationalePneumocystis pneumonia is a major cause of morbidity and mortality in HIV-infected subjects, cancer patients undergoing chemotherapy and solid organ transplant recipients. No vaccine is currently available. By chemical labeling coupled with proteomic approach, we have identified a putative surface protein (SPD1, Broad Institute gene accession number PNEG_01848) derived from single suspended P. murina cysts. SPD1 was expressed in an insect cell line and tested for vaccine development. MethodsMice were immunized with SPD1 plus adjuvant MF-59 by subcutaneous injection. Three weeks after the last immunization, CD4+ cells were depleted with anti-CD4 antibody GK1.5. The mice were then challenged with 2×105Pneumocystis organisms. Mice were sacrificed at 4 and 6weeks after PC challenge. Spleen/lung cells and serum were harvested. B cells and memory B cells were assessed via flow cytometry. Specific Pneumocystis IgG antibody was measured by ELISA before and after challenge. Infection burden was measured as real-time PCR for P. murina rRNA. ResultsNormal mice infected with Pneumocystis mounted a serum IgG antibody response to SPD1. Serum from rhesus macaques exposed to Pneumocystis showed a similar serum IgG response to purified SPD1. SPD1 immunization increased B cell and memory B cell absolute cell counts in CD4-depleted Balb/c mice post Pneumocystis challenge in spleen and lung. Immunization with SPD1 significantly increased specific Pneumocystis IgG antibody production before and after challenge. Mice immunized with SPD1 showed significantly decreased P. murina copy number compared with mice that did not receive SPD1 at 6weeks after challenge. ConclusionImmunization with SPD1 provides protective efficacy against P. murina infection. SPD1 protection against Pneumocystis challenge is associated with enhanced memory B cell production and higher anti–Pneumocystis IgG antibody production. SPD1 is a potential vaccine candidate to prevent or treat pulmonary infection with Pneumocystis.

Proof of Merit in New Diet Therapy Against Adult T-Cell Leukemia/Lymphoma: Applying Specific Amino Acid Dependency of Leukemia/Lymphoma Cells

Introduction:Adult T-cell leukemia/lymphoma (ATL) is highly aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Because ATL cells are very aggressive, cytotoxic combination chemotherapy is used as first-line therapy. However, ATL cells are often resistant to chemotherapy. The intensive chemotherapy induces severe myelosuppression, which requires frequent transfusions, and organ damages. Unfortunately, accumulation of these adverse events disables continuation of treatment in some patients. Recently antibody therapy which targets CC chemokine receptor 4 (CCR4) expressed on ATL cells has been approved for the treatment of relapsed ATL, but lymphoma-like massive ATL cells in lymph nodes or spleen are known to be resistant to antibody therapy. Therefore, we sought to develop a new strategy, and finally focused on amino acids as asparaginase is used for treatment of acute lymphoblastic leukemia.Methods:Amino acid dependency of HTLV-1-infected cells, including ATL cells, was examined in vitro using HTLV-1-infected cell-lines and ATL cells which were serially passaged after purification by flow cytometry from the sample of an acute-type ATL patient. These cells were cultured with stromal cells in the medium which lacked one of twenty amino acids for 2 weeks. Proliferation of ATL cells and influence on stromal cells was examined, and we picked up amino acids which were crucial only for ATL cells. We next prepared diets which lacked specific amino acids based on in-vitro screening, and examined the effect in vivo using xeno-transplantation models. In a lymphoma model, massed ATL cells were transplanted intraperitoneally into adult NOG mice, which were fed complete diets. Diets were unchanged or changed to restricted ones after 6 weeks, and maximum tumor size was compared after 10 weeks. In a leukemia model, primary ATL cells, which were sorted from peripheral blood of an acute-type ATL patient, were transplanted intravenously into neonatal NOG mice within 24 hours from the birth. Recipient mice were brought up by the mother fed complete diets. After 4 weeks, recipient mice were weaned from breast, and fed complete diets or restricted ones. Peripheral blood was followed over time by flow cytometry, and infiltration of ATL cells into various organs was analyzed after 8 weeks.Results:In-vitro studies revealed that HTLV-1-infected cells have dependency on specific amino acids in common, and it was noteworthy that ATL cells could not proliferate in valine-deficient conditions while the influence on co-cultured stromal cells was limited. Therefore, we specially prepared valine-depleted diets, and confirmed that density of valine was very low in peripheral blood and bone marrow of mice fed valine-depleted diets. In-vivo lymphoma models showed that no masses were observed macroscopically in all of mice fed valine-depleted diets. In-vivo systemic leukemia models showed that valine-restricted diets preferentially reduced ATL cells but not hemoglobin or platelets in peripheral blood as shown in figure 1. Additionally, pathological examinations showed that valine-deficient diets strongly prevented ATL cells from proliferating and infiltrating into organs, such as spleen, liver, and skin. As far as we examined histologically, there were no significant organ damages.Discussion and Conclusions:Our study uncovered that adult T-cell leukemia/lymphoma cells failed to proliferate in valine-depleted conditions. The inhibition induced by dietary valine restriction was drastic, whereas ATL cells could proliferate to greater or lesser degrees in conditions lacking other amino acids, even if essential amino acids were depleted. Additionally, valine is indispensable for the proliferation and maintenance of hematopoietic stem cells (HSCs) as we previously reported. Therefore, valine-deficient diets could successfully reduce leukemic stem cells of ATL. Moreover, there were no severe complications such as anemia, thrombocytopenia, and organ damages which are often seen in chemotherapy recipients. Lymphoma-like massive ATL cells, which are often resistant to antibody therapies, were also vulnerable to valine-depleted conditions. The issues seen in currently available therapies against aggressive leukemia and lymphoma could be solved by this diet therapy itself or by adding this therapy to other treatments with reduced toxicity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Rare Case of Non-typhoidal Salmonella SBP Leading to Empyema in Decompensated Cirrhosis

Introduction: Spontaneous bacterial peritonitis (SBP) is a common infection seen in cirrhotic patients, with bacterial translocation as a major mechanism of pathogenesis. Salmonella typhimurium is a gram negative non-typhoidal bacteria, which has been reported as an unusual cause of SBP in immunocompromised patients. We report a rare case of a salmonella empyema secondary to SBP in a decompensated cirrhotic. Case Report: A 63 year old Caucasian male with a history of cirrhosis secondary to chronic hepatitis C virus (HCV) was admitted with ascites and leukocytosis (WBC of 25.9 x109 per liter). Paracentesis revealed a WBC of 1196 (39% PMN's), consistent with a diagnosis of SBP. The patient was admitted and treated with intravenous albumin and antibiotics. Gram stain and culture of the ascitic fluid were negative. He clinically improved and was discharged on oral antibiotics after three days of hospitalization. Approximately one week later, the patient returned to the emergency department with progressive shortness of breath. He was hypoxic and had a significant leukocytosis (WBC of 19 x109 per liter). His abdominal exam was benign without any reoccurrence of ascites, but chest imaging demonstrated a right sided pleural effusion (Image 1 and Image 2). Thoracentesis was performed, which was consistent with an empyema. Gram stain of the pleural fluid showed gram negative rods and cultures grew non-typhoidal salmonella typhimurium (Image 3). Discussion: Non-typhoidal Salmonella is a rare cause of SBP that has been previously reported in the literature. Published case reports show an association of SBP with immunocompromised states such as malignancy, chemotherapy and organ transplant recipients. While a few cases of nontyphoidal Salmonella empyemas have been seen in the literature, this is the first reported case of SBP implicated as the cause of a Salmonella empyema. While a rare pathogen, Salmonella should be recognized as a cause of SBP in decompensated cirrhosis, especially in patients who are immunocompromised.

Host response to fungal infections - how immunology and host genetics could help to identify and treat patients at risk.

In spite of the ever-increasing incidence and poor outcome of invasive fungal infections in immune compromised patients, there is currently no reliable method to accurately predict the risk, to monitor the outcome and to treat these infections. Protective immunity against Candida and Aspergillus depends on a highly coordinated interaction between the innate and adaptive immune systems. Genetic and immunological defects in components of these networks result in increased risk of invasive fungal infections among patients undergoing chemotherapy or transplant recipients. We review the most important genetic and immunological factors that influence human susceptibility to Candida and Aspergillus infections and discuss the potential role of basic research to promote precision medicine for infectious diseases. We discuss how immunogenetic studies can help to provide tools for improved identification of high-risk patients and the development of tailored antifungal therapies.

Referral patterns between high- and low-volume centers and associations with uterine cancer treatment and survival: a population-based study of Medicare, Medicaid, and privately insured women

High-volume center surgery and gynecologic oncology care are associated with improved outcomes for women with uterine cancer. Referral patterns, from biopsy through to chemotherapy, may have patients interacting with high-volume centers for all, a portion, or none of their care. The relative frequency, the underlying factors that contribute to referral, and the potential impact of these referral patterns on treatment outcomes are unknown. We sought to analyze the referral patterns and subsequent impact of care sites on treatment for women with high- and low-risk uterine cancer. This is a population-based retrospective cohort study of uterine cancer cases from 2004 through 2009 in North Carolina. Using state cancer registry files linked to Medicare, Medicaid, and private payer insurance claims, we analyzed referral and treatment patterns by annual surgical volume (high ≥12/y). We examined clinical and demographic factors associated with referral and used modified Poisson regression to evaluate risk of referral, lymphadenectomy, and chemotherapy. Stratified Kaplan-Meier plots and Cox proportional hazard models were used to examine survival. A total of 2053 women were analyzed, including 34% (n= 677) with grade 3 histology. Of 1630 (80%) women with preoperative biopsies, referral patterns (biopsy to surgery) were: low volume to high volume (n= 652, 40%), followed by high volume to high volume (n= 605, 37%), then low volume to low volume (n= 318, 20%), and the rare high volume to low volume (n= 50, 3%). Women retained in low-volume centers after biopsy were older, were less likely to have private insurance, and had more comorbidities. High-risk histology (aRR, 1.14; 95% confidence interval, 1.04-1.25) was positively associated with referral, while Medicaid insurance was negatively associated with referral (aRR, 0.64; 95% confidence interval, 0.42-0.96). Most women (74%, n= 1557) had surgery at high-volume centers. Lymphadenectomy was less likely at low-volume centers (aRR, 0.71; 95% confidence interval, 0.64-0.77). Similarly, for high-risk patients, the relationship between low-volume center surgery and subsequent chemotherapy was aRR, 0.71 (95% confidence interval, 0.48-1.02). Of 290 women who received chemotherapy, the referral patterns (surgery to chemotherapy) were: high volume-all (high volume to high volume), high volume-hybrid (high volume to low volume, or low volume to high volume), and high volume-none (low volume to low volume). In all, 36% (n= 104/290) received chemotherapy at a low-volume center, the majority (68%, n= 71/104) of whom were referred from high-volume centers after surgery. Crude, unadjusted mortality risk of chemotherapy recipients differed by referral pattern (surgery to chemotherapy): high volume-all patients (hazard ratio, 1.0; referent), followed by high volume-hybrid (hazard ratio, 1.33; 95% confidence interval, 0.93-1.91) then high volume-none patients (RR,1.95; 95% confidence interval, 1.24-3.08). Most women with uterine cancer treated at high-volume centers arrive through referral, which is affected by age and type of insurance, in addition to histology. For high-risk women who require chemotherapy, survival may be related to the extent of treatment received at high-volume centers.

Allogeneic Transplantation in First Remission Improves Outcomes Irrespective of FLT3-ITD Allelic Ratio in FLT3-ITD–Positive Acute Myelogenous Leukemia

The adverse prognosis of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) in patients with acute myelogenous leukemia (AML) may depend on allelic burden. We compared postremission treatment with chemotherapy and hematopoietic stem cell transplantation (HSCT) in 169 FLT3-ITDmut intermediate cytogenetic risk AML patients with allelic ratio evaluable at diagnosis who achieved first complete remission (CR1) with induction therapy. To minimize selection bias, the analysis was limited to patients who remained in CR1 for at least 4 months (median time to HSCT) after achieving CR1, and propensity score matching was implemented. Sensitivity analysis including patients who remained in CR1 for at least 3 months was applied as well. HSCT in CR1 was associated with longer relapse-free survival (RFS) and overall survival (OS), with 3-year estimated rates of 18% and 24%, respectively (P < .001), for patients receiving chemotherapy and 46% and 54%, respectively (P < .001), for those undergoing HSCT. Multivariate regression models showed that HSCT remained statistically significant with improved RFS and OS independent of FLT3-ITD allelic ratio and NPM1 status. Irrespective of postremission therapy, relapse remains the main reason for treatment failure, with a 3-year incidence of 68% in chemotherapy recipients versus 41% in HSCT recipients. Allogeneic HSCT improved disease outcomes compared with chemotherapy after propensity score matching was applied. The improvement observed for RFS (hazard ratio [HR], 0.55; P = .09) and OS (HR, 0.58; P = .10) with HSCT as postremission therapy in patients who remained in CR1 for at least 4 months did not reach statistical significance; however, the sensitivity analyses including patients who remained in CR1 for at least 3 months showed significant improvement in both RFS (HR, 0.31; P = .002) and OS (HR, 0.27; P = .02) after propensity score matching. Our results indicate that HSCT in CR1 for AML FLT3-ITDmut patients is associated with longer RFS and OS. Innovative transplantation strategies to improve relapse incidence are urgently needed.

ReCAP: Hospitalizations in Older Adults With Advanced Cancer: The Role of Chemotherapy.

Hospital readmissions are often cited as a marker of poor quality of care. Limited data suggest some readmissions may be preventable depending upon definitions and available outpatient support. General criteria to define preventable and not preventable admissions were developed before data collection began. The records of sequential nonsurgical oncology readmissions were reviewed independently by two reviewers. When the reviewers disagreed about assigning admissions as preventable or not preventable, a third reviewer was the tie breaker. The reasons for assigning admissions as preventable or not preventable were analyzed. Seventy-two readmissions occurring among 69 patients were analyzed. The first two reviewers agreed that 18 (25%) of 72 were preventable and that 29 (40%) of 72 were not. A third reviewer found four of the split 25 cases to be preventable; therefore, the consensus preventability rate was 22 (31%) of 72. The most common causes of preventability were overwhelming symptoms in patients who qualified for hospice but were not participating in hospice and insufficient communication between patients and the care team about symptom burden. The most common reason for assignment of a not preventable admission was a high symptom burden among patients without strong indications for hospice or for whom aggressive outpatient management was inadequate. The median survival after readmission was 72 days. A substantial proportion of oncology readmissions could be prevented with better anticipation of symptoms in high-risk ambulatory patients and enhanced communication about symptom burden between patients and physicians before an escalation that leads to an emergency department visit. Managing symptoms in patients who are appropriate for hospice is challenging. Readmission is a marker of poor prognosis.

A review of complementary therapies for chemotherapy induced gastrointestinal mucositis

Administration of chemotherapy often leads to gastrointestinal mucositis (GIM). GIM manifests as nausea, abdominal pain and diarrhoea in recipients of chemotherapy. GIM is a major complication occurring in approximately 80% of patients receiving 5-flurouracil treatment. These side-effects may become so severe that significant dose reductions are required, ultimately affecting treatment efficacy and patient survival. Complementary and alternative medicine (CAM) is a growing area of public interest. This review will provide an overview of current knowledge of complementary medicinal therapies for chemotherapy induced GIM. An understanding of this evolving literature is useful in discussing these therapies with patients who are considering using them.

Multispecialist Care and Mortality in Hepatocellular Carcinoma

Multidisciplinary physician care has increased for many cancers yet little evidence exists for hepatocellular carcinoma (HCC). The purpose of this study was to explore the association between multispecialist care and mortality in HCC. Treated patients with an HCC primary diagnosis from 2000 to 2007 were studied using Surveillance, Epidemiology, and End Results-Medicare data. A surrogate variable for multidisciplinary care was defined-multispecialist care-as the number of disciplines among surgeons, radiology oncologist, intervention radiologist, hematologist/medical oncologist, gastroenterologist, and generalist in the pretreatment period. Multivariate survival analysis was conducted and adjusted for selection and survival bias. Of 3588 treated HCC patients, 1434 (40%) saw 1, 1343 (37%) saw 2, and 811 (23%) saw 3 or more specialists. Patients with multispecialist care received treatment that differed from patients who saw a single specialist. In propensity score-adjusted survival analysis, patients who saw 3 or more specialist types were associated with 10% (P=0.04) reduced mortality, compared with those who saw 1 specialist. When stratified by treatment received, patients on chemotherapy who saw 3 or more specialist types were associated with 28% (P=0.002) reduced mortality, compared with those who saw 1 specialist. Multispecialist care for treated HCC patients was associated with reduced mortality, particularly among chemotherapy recipients. While adjusting for selection and survival bias, our study is limited in capturing a causal relationship between coordinated multidisciplinary care and mortality. Our findings may provide support for the development of coordinated care delivery models but should be confirmed through more rigorous examination in future studies.

Control of norovirus outbreak on a pediatric oncology unit

Patients undergoing treatment for cancer with chemotherapy and hematopoietic stem cell recipients are at risk for severe morbidity caused by norovirus (NV). We describe a NV outbreak on the Memorial Sloan Kettering Cancer Center's pediatric oncology unit. Stool testing for diagnosis of NV was performed by real-time polymerase chain reaction (PCR). Twelve NV cases occurred; 7 were hospital acquired. Twenty-five health care workers reported NV compatible illness. Patient-to-patient transmission occurred once. The practices of the Centers for Disease Control and Prevention were supplemented with electronic surveillance, surrogate screening for NV, and heightened cleaning. Two additional cases occurred after implementation of interventions. Long-term shedding was detected in 2 patients. We describe interventions for controlling NV on a pediatric oncology unit. High-risk chronic shedders pose ongoing transmission risks. PCR is a valuable diagnostic tool but may be overly sensitive. Surrogate markers to assess NV burden in stool and studies on NV screening are needed to develop guidelines for high-risk chronic shedders.

Characteristics and critical function of CD8+ T cells in the Toxoplasma-infected brain.

The rise of the AIDS epidemic made the requirement for T cells in our continuous protection from pathogens critically apparent. The striking frequency with which AIDS patients exhibited profound neurological pathologies brought attention to many chronic infections that are latent within the immune-privileged CNS. One of the most common lethal opportunistic infections of these patients was with the protozoan parasite, Toxoplasma gondii. Reactivation of Toxoplasma cysts within the brain causes massive tissue destruction evidenced as multiple ring-enhancing lesions on MRI and is called toxoplasmic encephalitis (TE). TE is not limited to AIDS patients, but rather is a risk for all severely immunocompromised patients, including recipients of chemotherapy or transplant recipients. The lessons learned from these patient populations are supported by T cell depletion studies in mice. Such experiments have demonstrated that CD4+ and CD8+ T cells are required for protection against TE. Although it is clear that these T cell subsets work synergistically to fight infection, much evidence has been generated that suggests CD8+ T cells play a dominant role in protection during chronic toxoplasmosis. In other models of CNS inflammation, such as intracerebral infection with LCMV and experimental autoimmune encephalomyelitis (EAE), infiltration of T cells into the brain is harmful and even fatal. In the brain of the immunocompetent host, the well-regulated T cell response to T. gondii is therefore an ideal model to understand a controlled inflammatory response to CNS infection. This review will examine our current understanding of CD8+ T cells in the CNS during T. gondii infection in regards to the (1) mechanisms governing entry into the brain, (2) cues that dictate behavior within the brain, and (3) the functional and phenotypic properties exhibited by these cells.

Impaired T cell responsiveness to interleukin-6 in hematological patients with invasive aspergillosis.

Invasive mold infections (IMI) are among the most devastating complications following chemotherapy and hematopoietic stem cell transplantation (HSCT), with high mortality rates. Yet, the molecular basis for human susceptibility to invasive aspergillosis (IA) and mucormycosis remain poorly understood. Herein, we aimed to characterize the immune profile of individuals with hematological malignancies (n = 18) who developed IMI during the course of chemotherapy or HSCT, and compared it to that of hematological patients who had no evidence of invasive fungal infection (n = 16). First, we measured the expression of the pattern recognition receptors pentraxin 3, dectin-1, and Toll-like receptors (TLR) 2 and 4 in peripheral blood of chemotherapy and HSCT recipients with IMI. Compared to hematological controls, individuals with IA and mucormycosis had defective expression of dectin-1; in addition, patients with mucormycosis had decreased TLR2 and increased TLR4 expression. Since fungal recognition via dectin-1 favors T helper 17 responses and the latter are highly dependent on activation of the signal transducer and activator of transcription (STAT) 3, we next used phospho-flow cytometry to measure the phosphorylation of the transcription factors STAT1 and STAT3 in response to interferon-gamma (IFN-γ) and interleukin (IL)-6, respectively. While IFN-γ/STAT1 signaling was similar between groups, naïve T cells from patients with IA, but not those with mucormycosis, exhibited reduced responsiveness to IL-6 as measured by STAT3 phosphorylation. Furthermore, IL-6 increased Aspergillus-induced IL-17 production in culture supernatants from healthy and hematological controls but not in patients with IA. Altogether, these observations suggest an important role for dectin-1 and the IL-6/STAT3 pathway in protective immunity against Aspergillus.

Our 2015 approach to invasive pulmonary aspergillosis.

At the University Hospital of Cologne, in general two patient groups at high risk for invasive aspergillosis receive posaconazole prophylaxis: Acute myelogenous leukaemia patients during remission induction chemotherapy and allogeneic haematopoietic stem cell transplant recipients. Other patients at risk undergo serum galactomannan testing three times weekly. At 72-96h of persisting fever despite broad-spectrum antibiotics, or at onset of lower respiratory tract symptoms a thoracic computed tomography (CT) scan is performed. Without lung infiltrates on CT, IPA is ruled out. In lung infiltrates not suggestive for IPA mycological confirmation is pursued. In patients without posaconazole prophylaxis empiric caspofungin will be considered. CT findings typical for IPA prompt targeted treatment, and mycological confirmation. Bronchoalveolar lavage (BAL) is most important for cultural identification and susceptibility testing, and facilitates diagnosing other pathogens. BAL performance is virtually independent of platelet counts. If despite suggestive infiltrates BAL does not yield the diagnosis, CT-guided biopsy follows as soon as platelet counts allow. Surgery can also be beneficial in diagnosis and treatment of IPA. If the diagnosis of IPA is not established, mucormycosis is a valid concern. In patients with breakthrough IPA during posaconazole prophylaxis liposomal amphotericin B is the drug of choice. If no posaconazole prophylaxis was given, voriconazole is the treatment of choice for IPA.