Elevated soluble CD23 level indicates increased risk of B cell non-Hodgkin’s lymphomas: evidence from a meta-analysis

Abstract

The aim of the present study was to determine whether circulating soluble CD23 (sCD23) was associated with B cells non-Hodgkin's lymphomas (B-NHL). PubMed, EMBASE, and ISI Web of Science were extensively searched without language restriction. Data was extracted in a standardized data collection sheet after two reviewers scanned studies independently. The association between sCD23 and NHL was indicated as odds ratio (OR) along with its related 95% confidence interval (95% CI). Meta-analysis was conducted via RevMan 5.3. A total of five studies, which included 964 B-NHL patients and 1243 matched controls without B-NHL, among which 257 were HIV-positive donors and 986 were general controls, were included in our study. Meta-analysis revealed a significant association between peripheral sCD23 level and B-NHL in HIV-positive samples (OR 1.66, 95% CI 1.25, 2.20; P = 0.0005) as well as the general population (OR 2.51; 95% CI 1.71, 3.86; P < 0.00001). Meta-analysis, stratified by sampling time prior to diagnosis, indicated potential HIV-NHL patients are 2.34-folds more likely to have higher blood sCD23 level, although this association is statistically meaningful only during 3–5 years prior to diagnosis (95% CI 1.27, 4.33). Subgroup analysis based on B-NHL type demonstrated a significant association between sCD23 level and diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL). The findings of our study indicate a positive association of circulating sCD23 level and B-NHL risks and highlight the possibility of sCD23 as a predictive marker of B-NHL. However, to better understand the underlying mechanism, further studies are needed.

https://ift.tt/2tzbDCR

Impact of hematopoietic stem cell transplantation in patients with relapsed or refractory mantle cell lymphoma

Abstract

Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n = 111) or allogeneic (n = 51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P = 0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were > 60 years of age at HCT (P = 0.017), higher score of HCT-specific comorbidity index at HCT (P = 0.033), and receiving MCEC (ranimustine + carboplatin + etoposide + cyclophosphamide) regimen (P = 0.017), while higher performance status at HCT (P = 0.011) and longer interval from diagnosis to HCT (P = 0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.

https://ift.tt/2lwGFYo

Significance of circulating Epstein-Barr virus DNA monitoring after remission in patients with extranodal natural killer T cell lymphoma

Abstract

Circulating Epstein-Barr virus (EBV)-DNA has been established as a useful parameter for diagnosis and predicting prognosis in patients with extranodal natural killer T cell lymphoma (ENKTL); however, the role of monitoring of circulating EBV-DNA after complete remission (CR) is not well established. From January 2008 to August 2016, 328 ENKTL patents were enrolled in 2 lymphoma cohorts. Of 171 patients achieved a CR, 81 had available monitoring data for circulating EBV-DNA with negative post-treatment EBV-DNA. Measurement of circulating EBV-DNA was performed from unfractionated whole blood and calculated according to WHO international standards. Median duration of follow-up was 40.4 months. In 31 of the 81 patients (38.8%), circulating EBV-DNA was detected at least once during follow-up, and 16 of these patients (51.6%) experienced relapse. In contrast, only 7 out of 50 (14.0%) patients with consistently undetectable circulating EBV-DNA experienced relapse (p < 0.001). In multivariate analysis, positive conversion of circulating EBV-DNA was the only independent prognostic factor for occurrence of relapse (HR = 6.552, p < 0.001), progression-free survival (HR = 4.549, p = 0.01), and overall survival (HR = 8.726, p < 0.001). Patients with a higher level of circulating EBV-DNA than 3310 IU/mL (3.52 log₁₀ IU/mL) showed a strong tendency to relapse (73.3 vs. 31.3%, p = 0.019). In conclusion, positive conversion of circulating EBV-DNA was a valuable indicator of relapse and inferior survival, especially if the level was higher than 3310 IU/mL in ENKTL patients had achieved CR. Close follow-up is necessary for patients developed detectable circulating EBV-DNA after remission.

https://ift.tt/2yES2XG

IgG synthesis rate and anti-myelin oligodendrocyte glycoprotein antibody in CSF may be associated with the onset of CNS demyelination after haplo-HSCT

Abstract

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and effective therapy for hematology patients, but it usually has many complications, such as neurological complications. As one of the neurological complications following haplo-HSCT, immune-mediated demyelinating diseases of the central nervous system (CNS) seriously affect a patient's quality of life. However, the incidence, risk factors, and pathogenesis of CNS demyelination are not very well understood. Thirty of the 1526 patients (1.96%) suffered from CNS demyelination. In univariate analysis, we found that blood-brain barrier (BBB) permeability and the CSF IgG synthesis index (IgG-Syn) were related to the occurrence of CNS demyelination (p < 0.05). In a multivariate analysis, the IgG-Syn (OR = 1.017, 95% CI 1.003–1.031, p = 0.019) and CSF anti-myelin oligodendrocyte glycoprotein antibody (MOG.Ab) (OR = 12.059, 95% CI 1.141–127.458, p = 0.038) were independently associated with the onset of CNS demyelination. We also studied the possible pathogenesis of CNS demyelination. Immune reconstitution (the cell proportions of CD19⁺ B cells, CD3⁺ T cells, and CD4⁺ T cells); the counts of leucocytes, lymphocytes, monocytes, and platelets; and the levels of immunoglobulins A, G, and M 30, 60, and 90 days after HSCT showed no significant differences between CNS demyelination and no demyelination (p > 0.05). The probabilities of overall survival showed no significant differences between patients with and without demyelination (p > 0.05). Only four deaths in 30 patients, but bringing projected survival to less than 20%.We imply that IgG-Syn and CSF MOG. Ab may be associated with the onset of CNS demyelination during 2 weeks of neurological symptoms in patients with brain or spinal cord MRI abnormality. Immune reconstitution may not be the pathogenesis of CNS demyelination.

https://ift.tt/2luBMz7

Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a multicenter retrospective analysis

Abstract

Bendamustine plus rituximab (BR) showed efficacy and safety in indolent lymphomas and mantle cell lymphoma. However, there were limited experiences of real-world practice of BR in diffuse large B cell lymphoma (DLBCL). In this study, we report the Korean experiences with BR in relapsed or refractory DLBCL who are not eligible for intensive chemotherapy and autologous stem cell transplantation. This is an observational, multicenter, retrospective analysis. Between December 2011 and December 2015, a total of 58 patients with relapsed or refractory DLBCL were treated with BR in 11 tertiary hospitals in Korea. Patients received an intravenous (IV) infusion of rituximab at a dose of 375 mg/m² on day 1. On days 2 and 3, patients received an IV infusion of bendamustine at doses of 120 or 90 mg/m². Median age was 69 (range 18–86), 74.1% had stage III or IV disease, and 67.2% showed high-intermediate or high International Prognostic Index scores at diagnosis. In an intention-to-treat analysis, 18 patients (31.0%) showed a complete response and 14 (24.1%) showed a partial response, resulting in an overall response rate of 55.1%. The median duration of the response was 3.7 months (range 1.0–47.2 months). The median progression-free survival was 3.9 months (95% confidence interval [CI], 2.4–5.4 months), and the median overall survival was 6.7 months (95% CI, 4.7–8.7 months). The most common grade 3/4 adverse event was neutropenia (n = 40; 68.9%). Febrile neutropenia was observed in 11 patients (18.9%). Grade 3/4 thrombocytopenia was observed in 34 patients (58.6%). Our study confirmed the high efficacy and acceptable toxicity profile of BR in relapsed or refractory DLBCL patients. However, we need to closely observe the higher tendency of grade 3/4 hematological toxicities in Korean patients.

https://ift.tt/2yG6grb

Late-onset hemophagocytic lymphohistiocytosis with varicella zoster virus and Epstein-Barr virus co-infection after umbilical cord blood transplantation

https://ift.tt/2lwGDQg

A patient with B-cell acute lymphoblastic leukemia with PAX5-ETV6 rearrangement with dic(9;12)(p13;p13) identified by chromosomal microarray

https://ift.tt/2yOB6OL

Large granular lymphocytic leukemia-associated peripheral neuropathy

https://ift.tt/2lwyo6H

BAALC and ERG expression levels at diagnosis have no prognosis impact on acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract

Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT.

https://ift.tt/2tBp999

Efficacy and safety of decitabine against cutaneous granuloblastic sarcoma: a case report

https://ift.tt/2lwGFaQ

The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review

Abstract

CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017. The pooled severe CRS proportion was 29.3% (95% confidence interval [CI] 12.3–49.1%) in B-ALL, 38.8% (95%CI 12.9–67.6%) in B-CLL, and 19.8% (95%CI 4.2–40.8%) in B-NHL. In the univariate meta regression analysis, the proliferation of CD19-CAR-T cell in vivo was correlated with the severe CRS. Specifically, total infusion cell dose contributed to the severe CRS occurring in B-ALL patients but not in B-CLL or B-NHL patients. Tumor burden was strongly associated with the severity of CRS in B-ALL. Besides, post-HSCT CD19 CAR-T cell infusion represented lower severe CRS incidence. Further investigations into the risk factors of CRS in B-CLL and B-NHL are needed.

https://ift.tt/2yEavUb

Eculizumab treatment for ischemic enteritis accompanied with paroxysmal nocturnal hemoglobinuria: a case report and literature review

https://ift.tt/2lvVIBG

Autoimmune disorders are common in myelodysplastic syndrome patients and confer an adverse impact on outcomes

Abstract

The coexistence of autoimmune disorders (AD) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely recognized, although with distinct results regarding their prevalence and impact on the outcomes of the underlying hematological process. This study was aimed to analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both the presence of clinical symptoms or compatible serological tests. In total, 48% patients were diagnosed as having AD, being hypothyroidism the most commonly reported clinical AD (8%) and antinuclear antibodies the most frequent serological parameter identified (23.2%). The presence of AD was associated with female gender, lower hemoglobin levels, and higher IPSS-R. Overall survival for patients with AD was inferior to those with no AD (69 vs. 88% at 30 months; HR 2.75, P = 0.008). Notably, clinical but not isolated immune serological parameters had an impact on the outcomes of patients with AD. Finally, in a multivariate analysis, the presence of AD (HR 2.26) along with disease risk categories (very low and low vs. intermediate, high, and very high IPSS-R; HR 4.62) retained their independent prognostic value (P < 0.001). In conclusion, AD are prevalent in MDS and CMML patients and have prognostic implications, especially in lower-risk MDS patients.

https://ift.tt/2tAJ3kC

Light chain monoclonal gammopathy of undetermined significance is characterized by a high disappearance rate and low risk of progression on longitudinal analysis

Abstract

We determined the 10-year progression rate of light chain monoclonal gammopathy of undetermined significance (LCMGUS) and investigated potential associations with cancer utilizing the German population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4814 men and women aged 45–75 years. Serum samples from baseline (2000–2003) and five-year (2006–2008) and 10-year (2011–2015) follow-up examinations were screened for monoclonal free light chains (FLC). LCMGUS was defined as abnormal FLC ratio, increase of involved FLC with complete loss of immunoglobulin heavy chain, and absence of a history of lymphoproliferative disease (LPD). Seventy-five individuals with LCMGUS were identified across all three evaluation time points (median age 64 years; 43 (57%) male; FLCR > 1.65 65 (87%); FLCR ≤ 0.65 10 (13%)). After a median observation time of 11.5 years, none of the LCMGUS cases had progressed to overt LPD; in particular, we did not observe incident light chain multiple myeloma. On serial analysis 17/31 (55%), LCMGUS could not be confirmed and disappearance of the monoclonal protein was associated with low concentrations of the involved FLC. Individuals with LCMGUS had a 1.5-fold increased risk of cancer but did not show differences in overall survival or renal function as compared to individuals with normal FLC. In conclusion, LCMGUS represents a relatively benign condition with a high disappearance rate of the monoclonal protein on longitudinal analysis and normal overall survival at least in the population-based setting.

https://ift.tt/2lv6rMF

Diffuse large B cell lymphoma (DLBCL): bilateral vanishing tibiae

https://ift.tt/2txjq48

Outcomes of patients with myelofibrosis treated with compassionate use pacritinib: a sponsor-independent international study

Abstract

Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients. Thirty-three patients benefitting from PAC on clinical trial prior to the hold were allowed to resume therapy on an individual, compassionate-use basis. This study reports the detailed outcomes of 19 of these PAC retreatment patients with a median follow-up of 8 months. Despite a median platelet count of 49 × 10⁹/L at restart of PAC, no significant change in hematologic profile was observed. Grade 3/4 adverse events of epistaxis (n = 1), asymptomatic QT prolongation (n = 1), and bradycardia (n = 1) occurred in three patients within the first 3 months of retreatment. One death due to catheter-associated sepsis occurred. The median time to discontinuation of PAC therapy on compassionate use for all 33 patients was 12.2 (95% CI 8.3—NR) months. PAC retreatment was associated with modest improvement in splenomegaly without progressive myelosuppression and supports the continued development of this agent for the treatment of MF second line to ruxolitinib or in the setting of treatment-limiting thrombocytopenia.

https://ift.tt/2lxUDJq

Isolated Richter’s syndrome of the brain: diagnosis in the eye of the beholder

https://ift.tt/2yKOkf0

Eltrombopag as initial monotherapy for severe aplastic anemia—a case report

https://ift.tt/2lyNadm

Brentuximab vedotin is effective for rheumatoid arthritis in a patient with relapsed methotrexate-associated Hodgkin lymphoma

https://ift.tt/2tzbi33

Clinical impact of underweight status at diagnosis on elderly patients with acute myeloid leukemia: a retrospective study of JALSG GML200

https://ift.tt/2lvpJS1

Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia

Abstract

Purpose

Malignant hyperthermia (MH) is an inherited muscle disorder caused by abnormal elevations of intracellular calcium (Ca²⁺) in skeletal muscle. There are several reports of myotoxicity caused by local anesthetics, and the increased intracellular Ca²⁺ is considered to be an important cause. However, there is insufficient evidence regarding myotoxicity in MH-susceptible individuals when large doses of local anesthetics are administered. This study investigated the effect of MH predisposition on myotoxicity.

Methods

Human skeletal muscle samples were obtained from 22 individuals to determine susceptibility to MH, and were evaluated according to whether their Ca²⁺-induced Ca²⁺ release (CICR) rates were accelerated or not. This study was performed using surplus muscle that remained after the CICR rate test. We calculated the 50% effective concentration (EC₅₀) values of three local anesthetics, namely lidocaine, levobupivacaine, and ropivacaine using the ratiometric dye Fura-2 AM. Significance was tested using the unpaired t test.

Results

In the accelerated and unaccelerated groups, respectively, the mean ± SD of the EC₅₀ values were 1.52 ± 0.72 and 1.75 ± 0.37 mM for lidocaine (p = 0.42), 0.72 ± 0.36 and 0.79 ± 0.46 mM for levobupivacaine (p = 0.68), and 1.21 ± 0.35 and 1.62 ± 0.57 mM for ropivacaine (p = 0.06). These values were similar in individuals with and without MH predisposition.

Conclusion

The myotoxicity of local anesthetics was equivalent in individuals with and without predisposition to MH.

https://ift.tt/2KhUZPo

Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

Ovarian stimulation for IVF and risk of primary breast cancer in <i>BRCA1/2</i> mutation carriers, Published online: 25 June 2018; doi:10.1038/s41416-018-0139-1

Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

https://ift.tt/2txhObB

Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating <i>MDR1</i> transcription, Published online: 25 June 2018; doi:10.1038/s41416-018-0119-5

Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

https://ift.tt/2K2HarQ

Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

https://ift.tt/2tAwplF

Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription

https://ift.tt/2tBd1os

Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats

Cancer Science, EarlyView.


https://ift.tt/2K5ZErH

Fine mapping in TERT‐CLPTM1L region identified three independent lung cancer susceptibility signals: A large‐scale multi‐ethnic population study

Molecular Carcinogenesis, EarlyView.


https://ift.tt/2trSH9M

Predicting parental distress among children newly diagnosed with craniopharyngioma

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2Kjh4gt

Diagnosis of Beckwith–Wiedemann syndrome in children presenting with Wilms tumor

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2MRU9dE

Living with Keith

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2KjgX4x

Upfront eltrombopag monotherapy induces stable hematologic remission in pediatric patients with nonsevere idiopathic aplastic anemia

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2tocNlc

Therapeutic response of metastatic angiomatoid fibrous histiocytoma carrying EWSR1‐CREB1 fusion to the interleukin‐6 receptor antibody tocilizumab

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2MmzHk9

Propranolol versus steroids for the treatment of ulcerated infantile hemangiomas

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2tocAOW

Olanzapine for chemotherapy‐induced nausea: Lessons learned from child and adolescent psychiatry

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2MjejfC

Issue Information

Pediatric Blood &Cancer, Volume 65, Issue 8, August 2018.


https://ift.tt/2ttfoKM

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2ImYgeu

Surgically resected T1‐ and T2‐stage esophageal squamous cell carcinoma: T and N staging performance of EUS and PET/CT

Cancer Medicine, EarlyView.


https://ift.tt/2K6ch5N

Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

Cancer Medicine, EarlyView.


https://ift.tt/2KkTwYn

Trends in colorectal cancer incidence among younger adults—Disparities by age, sex, race, ethnicity, and subsite

Cancer Medicine, EarlyView.


https://ift.tt/2KijA9S

Financial hardship associated with colorectal cancer survivorship: The role of asset depletion and debt accumulation

Psycho-Oncology, EarlyView.


https://ift.tt/2yAbHbq

Fear of cancer recurrence and death anxiety

Psycho-Oncology, EarlyView.


https://ift.tt/2lvZNpq

Gender role conflict, emotional approach coping, self‐compassion, and distress in prostate cancer patients: A model of direct and moderating effects

Psycho-Oncology, EarlyView.


https://ift.tt/2yNyvEL

High levels of serum CA15‐3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non‐pathological complete response after neoadjuvant chemotherapy

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2tDEy94

Staged margin‐controlled excision (SMEX) for lentigo maligna melanoma in situ

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2MWqno3

CSF3R mutations are frequently associated with abnormalities of RUNX1, CBFB, CEBPA, and NPM1 genes in acute myeloid leukemia

Cancer, EarlyView.


https://ift.tt/2Ikempb

A home‐based mentored vegetable gardening intervention demonstrates feasibility and improvements in physical activity and performance among breast cancer survivors

Cancer, EarlyView.


https://ift.tt/2K536me

Evaluation of 2 breast cancer risk models in a benign breast disease cohort

Cancer, EarlyView.


https://ift.tt/2ImUUIr

Patterns of treatment failure in salivary gland cancers

Publication date: July–August 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 4
Author(s): Mateusz Szewczyk, Paweł Golusiński, Jakub Pazdrowski, Piotr Pieńkowski, Sławomir Marszałek, Jacek Sygut, Wojciech Golusiński
AimThe purpose of the study was to publish our experience of salivary gland cancer treatment with large number of patients treated at a single institution.BackgroundSalivary gland cancers are rare tumors of the head and neck representing about 5% of cancers in that region and about 0.5% of all malignancies. Due to the rarity of the disease, most of the studies regarding treatment outcome consist of low number of patients, thus making it difficult to draw conclusions.Material and methods115 patients with primary salivary gland cancer were included in a retrospective study. The subsites of tumor were the parotid gland (58% patients), submandibular gland (19%) and minor salivary glands (23%). All patients underwent primary surgical resection. The following were collected: age, stage of the disease, T status, N status, grade of tumor, perineurial invasion, lymphovascular invasion, extracapsular spread, final histological margin status and postoperative treatment. Details of local, regional or distant recurrence, disease free survival and overall survival were included.ResultsThe majority (65%) of patients presented in early stage, T1 and T2 tumors. 81% of patients were N0. Free surgical margins were achieved in 18% of patients, close in 28% patients and positive surgical margins in 54% (62) patients. Factors that significantly increased the risk of recurrence: T stage (p=0.0006); N-positive status (p<0.0001); advanced stage of the disease (p<0.0001); high grade of tumor (p=0.0007); PNI (p=0.0061); LVI (p=0.0022); ECS (p=0.0136); positive surgical margins (p=0.0022). On multivariate analysis, high grade of tumor and positive surgical margins remained significant independent adverse factors for recurrence formation.ConclusionsThis report shows a single institution results of oncological treatment in patients with malignant salivary gland tumors, where positive surgical margins strongly correlate with patients' worse outcome. Whether to extend the procedure, which very often requires sacrificing the nerve is still a question of debate.



https://ift.tt/2MlUsfE

Infantile Hemangioma Presenting as Colocolic Intussusception in an Infant Case Report with Review of Pathologic Lead Points

Infantile hemangioma (IH) is one of the most common vascular anomalies of early childhood and is usually recognized in the first few weeks to months of life as a solitary cutaneous lesion. This report documents our experience with a GLUT-1 positive IH presenting as the pathologic lead point in a colocolic intussusception in a 10-week-old infant who had no skin lesions. Literature suggests approximately 2% of all children presenting with an intussusception require surgical intervention; however, an IH as the pathologic lead point is unique.

https://ift.tt/2ImhYa8

Erratum to “Severe Drug-Induced Agranulocytosis Successfully Treated with Recombinant Human Granulocyte Colony-Stimulating Factor”

https://ift.tt/2MlzrSB

A Case of Sirenomelia Associated with Hypoplastic Left Heart with a Healthy Co-Twin: A Rare Entity

Sirenomelia is a rare developmental malformation and is incompatible to life. The incidence of sirenomelia, as recorded in the literature, is estimated to be approximately between 1.5 and 4.2 per 1,00,000 births. Around 15% of sirenomelia cases are associated with twin pregnancy, most often in monozygotic cases with an incidence of 7%. In monozygotic twins, the risk of sirenomelia is nearly 100–150 times higher as compared to dizygotic twins or singleton pregnancies. Until now, only two cases of sirenomelia associated with hypoplastic left heart have been reported in the literature. Here, we present a monozygotic twin pregnancy, where one fetus was diagnosed with sirenomelia associated with hypoplastic left heart syndrome and the co-twin was absolutely healthy.

https://ift.tt/2K2wYQ4

Successful Treatment of Severe Atopic Dermatitis with Calcitriol and Paricalcitol in an 8-Year-Old Girl

Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.

https://ift.tt/2ImoU7k

X-Linked Chronic Granulomatous Disease: Initial Presentation with Intracranial Hemorrhage from Vitamin K Deficiency in Infant

Vitamin K deficiency bleeding (VKDB) is a life-threatening condition and can be found in children as early as neonatal period with early onset intracranial hemorrhage (ICH). Here, we reported a 1-year-old boy who initially presented with intracranial hemorrhage secondary to vitamin K deficiency since 3 months of age and later found to have XL-CGD which was complicated by malabsorption due to severe vaccine-associated mycobacterial disease.

https://ift.tt/2K6tqwn

Triage for selection to colonoscopy?

Publication date: Available online 23 June 2018
Source:European Journal of Surgical Oncology
Author(s): Mathias Mertz-Petersen, Thomas B. Piper, Jakob Kleif, Linnea Ferm, Ib Jarle Christensen, Hans J. Nielsen
Implementation of population screening for colorectal cancer by direct colonoscopy or follow-up colonoscopy after a positive fecal blood test has challenged the overall capacity of bowel examinations. Certain countries are facing serious colonoscopy capacity constraints, which have led to waiting lists and long-time latency of follow-up examinations. Various options for improvement are considered, including increased cut-off values of the fecal blood tests. Results from major clinical studies of blood-based, cancer-associated biomarkers have led to focus, however, on a triage concept for improved selection to colonoscopy. The triage test may include subject age, concentration of hemoglobin in a feces test and a combination of certain blood-based cancer associated biomarkers. Recent results have indicated that triage may reduce the requirements for colonoscopy by around 30%. Such results may be advantageous for the capacity, the heath budgets and in particular, the subjects, who do not need an unnecessary, unpleasant and risk-associated bowel examination.



https://ift.tt/2yCSs0H

Prognostic impact of residual disease in simultaneous additional excision specimens after one-step breast conserving therapy with negative final margin status in primary breast cancer

Publication date: Available online 23 June 2018
Source:European Journal of Surgical Oncology
Author(s): Steffen Kahlert, M. Kolben Theresa, Elisa Schmoeckel, Bastian Czogalla, Anna Hester, Tom Degenhardt, Cordula Kempf, Sven Mahner, Nadia Harbeck, Thomas Kolben
PurposeThe purpose of this study was the evaluation of risk factors for local recurrence after breast conserving surgery (BCS) with special focus on the impact of residual disease in specimens of simultaneous additional excisions (AE) from the tumor cavity on patients´ outcome in patients with negative final margin status after one-step BCS.MethodsThis study was designed as a single center retrospective cohort study. Patients with primary non-metastatic breast cancer treated by one-step BCS with pathologically confirmed negative resection status between 1990 and 2006 were included. Ipsilateral breast tumor recurrence (IBTR) and overall survival (OS) were evaluated by Kaplan-Meier-estimates. A multivariate Cox proportional hazards regression model was used to identify potential independent prognostic factors associated with the risk of IBTR.ResultsA total of 1081 patients were included in this analysis. Simultaneous additional excisions were performed in 79.4% of patients (tumor positive: 12.2%). Median follow-up after primary diagnosis was 124 months. The IBTR rate after 15 years was significantly higher in the group with tumor positive AE (no AE (10.2%) vs. AE tumor positive (27.5%) p=0.002; AE tumor negative (14.0%) vs. AE tumor positive (27.5%) p=0.008). The OS rate did not differ significantly between groups. Multivariate analysis revealed residual cancer in AE being associated with a significantly increased relative risk of IBTR of 2.0 (p=0.014).ConclusionIn the current analysis residual disease in simultaneous additional excisions was associated with an increased risk for IBTR despite negative final margin status. This should be considered in the overall therapeutic concept.



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Survival Outcomes and Interval Between Lymphoscintigraphy and SLNB in Cutaneous Melanoma- Findings of a Large Prospective Cohort Study

Publication date: Available online 23 June 2018
Source:European Journal of Surgical Oncology
Author(s): Fionnuala M. O'Leary, Clare J. Beadsmoore, Davina Pawaroo, John Skrypniuk, Martin J. Heaton, Marc D. Moncrieff




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A systematic analysis highlighting deficiencies in reported outcomes for patients with stage IV colorectal cancer undergoing palliative resection of the primary tumour

Publication date: Available online 23 June 2018
Source:European Journal of Surgical Oncology
Author(s): Deena P. Harji, Abigail Vallance, Jenny Selgimann, Simon Bach, Faheez Mohammed, Julia Brown, Nicola Fearnhead
BackgroundManagement of the primary tumour in the presence of unresectable metastatic colorectal cancer (mCRC) is controversial. The role of primary tumour resection (PTR) has been investigated by a number of retrospective cohort studies, with a number on going randomised controlled trials. The aim of this study was to identify the clinical and patient-reported outcomes currently reported in studies that evaluate the role of PTR in mCRC.MethodsLiterature searches were performed in MEDLINE (via OvidSP) (1966– June 2017), EMBASE (via OvidSP) and the Cochrane Library using terms related to colorectal cancer and primary tumour resection. All studies documenting outcomes following palliative PTR were included. Eligible articles were assessed using the Risk of Bias In Non-Randomised Studies of Intervention (ROBINS-I) tool.ResultsOf 11,209 studies screened, 59 non-randomised studies reporting outcomes on 331,157 patients were included. Patient characteristics regarding performance status and co-morbidity were recorded in 26 (44.1%) and 17 (28.8%) studies. The chemotherapy regime used was reported in 27 (45.8%) studies. The operative setting and the operative approach was reported in 42 (71%) and 14 (23.7%) studies. Post-operative mortality and morbidity were reported in 33 (55.9%) and 35 (59.3%) of studies. Overall survival was reported in 49 (83.1%) of studies, with 5 different definitions identified. Quality of life was only reported in 1 (1.7%) study.ConclusionThis study demonstrates significant heterogeneity in the selection and definition of outcomes reported following PTR in mCRC. There is significant heterogeneity with a significant under-reporting of important outcomes such as treatment related adverse events and patient reported outcomes.



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30-day and long-term outcome following salvage surgery for squamous cell carcinoma of the anus

Publication date: Available online 23 June 2018
Source:European Journal of Surgical Oncology
Author(s): T.B. Pedersen, P. Gocht-Jensen, M.F. Klein
IntroductionSquamous cell carcinoma of the anus (SCCA) is a rare condition. First line treatment is combined chemo-radio therapy. As many as a third of patients undergoing CRT will experience recurrence. These patients often undergo salvage surgery with an extended abdominoperineal excision. The aims of this study were 1) to assess and evaluate 30-day postoperative morbidity and mortality after salvage surgery for recurrent SCCA, and furthermore, 2) to examine secondary recurrence and long-term mortality after salvage surgery for recurrent SCCA.Material and MethodsRetrospective evaluation of all patients undergoing salvage surgery for SCCA at Copenhagen University Hospital Herlev between 1st of January 2011 and 31th December 2016.ResultsForty-seven patients were identified. 30-day postoperative mortality was 4%. The most common postoperative complication was perineal wound defects. Within the follow-up period of median 20(1-80) months, secondary recurrence occurred in 30% of patients. Median disease free survival was 32 months. Secondary recurrence was significantly more frequent in patients with R1 resection and pN≥1. Within the follow-up period of median 25(0-80) months, mortality was 40%. Overall median survival was 39 months. Secondary recurrence was associated with a significantly higher risk of death within the follow-up period.ConclusionSalvage surgery for relapse of squamous cell carcinoma of the anus is a safe procedure with a good short-term outcome. Secondary recurrence was more frequent in patients with R1-resection and pN≥1. More than one third of the patients died within the follow-up period, and mortality was significantly higher in the group of patients with secondary recurrence.



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Acute Hemolytic Transfusion Reaction in Group B Recipient Associated with Group A Apheresis Platelet Donor: Case Report and Literature Review

Acute hemolytic transfusion reaction is a known but rare potential adverse event related to platelet transfusion. Most reported cases of platelet-related hemolytic transfusion reaction have resulted from transfusion of platelets from group O donor to group A recipient. We identified only one prior case report in the literature of hemolytic transfusion reactions resulting from transfusion of apheresis platelets from group A donor to group B recipient. In that case report, two platelet units were obtained from a single donation and transfused into two separate patients. Both patients exhibited acute hemolytic reactions. The donor is reported to have high anti-B titers, as well as report of probiotic use. We report a case of acute hemolytic reaction in group B recipient following transfusion of apheresis platelets from group A donor with high-titer anti-B but unknown status of probiotic use. This case demonstrates that while low, there still exists potential risk for hemolysis from out-of-group A plasma transfusion.

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An Unusual Case of Gullo’s Syndrome Concomitant with Serious Endometriosis Disease in a Postmenopausal Woman

Gullo's syndrome is a singular physiological phenomenon defined by an abnormal increase in serum pancreatic enzyme levels that may occur in healthy subjects in the absence of pancreatic disorders. During routine health examination in a 54-year-old postmenopausal woman with severe endometriosis, elevated values of serum amylase and lipase were fortuitously observed (198 and 1461 U/L, resp.). Over five years of regular pancreas surveillance, all clinical, biological, and imaging investigations were normal. However, the pancreatic enzyme levels have shown considerable fluctuations including some episodic transient normalization. The description of this benign pancreatic hyperenzymemia case incidentally associated with endometriosis disease is a very rare clinical situation. More in-depth documentation of this phenomenon may help clinicians to avoid unnecessary diagnostic management approaches and reassure the concerned patients that this affection would not be so worrying.

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LBA-002Overall survival results from a phase III trial of trifluridine/tipiracil versus placebo in patients with metastatic gastric cancer refractory to standard therapies (TAGS)

Background: Trifluridine/tipiracil (FTD/TPI), an orally administered combination agent approved for patients with refractory metastatic colorectal cancer, demonstrated promising clinical activity in a refractory gastric cancer Japanese Phase II trial. Therefore, we initiated the TAGS study (NCT02500043) to evaluate the efficacy and safety of FTD/TPI in patients with heavily pretreated metastatic gastric cancer (mGC).

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LBA-004Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Background: Patients with chemotherapy-refractory microsatellite stable (MSS) metastatic colorectal cancer (CRC) are a population with limited treatment options and relatively short survival. Atezolizumab (an anti–PD-L1 mAb) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, leading to the re-invigoration of tumour-specific T-cell immunity. Cobimetinib inhibits MEK1/MEK2 in the MAPK pathway, and blocking the MAPK pathway has been shown to favourably alter the tumour, tumour microenvironment and T-cell responses to promote anti-tumour immune activity. We hypothesized that combining atezolizumab with cobimetinib may allow better immune recognition and generate greater anti-tumour effects than either agent alone in MSS/microsatellite instability-low (MSI-L) metastatic CRC. Here we report the primary analysis results from IMblaze370 (NCT02788279), a global, multi-centre, open-label, randomised Phase III trial comparing atezolizumab+cobimetinib and atezolizumab monotherapy with standard-of-care regorafenib in patients with previously treated, unresectable locally advanced or metastatic CRC.

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LBA-001Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: Pooled efficacy and safety across two global randomized Phase 3 studies (REACH-2 and REACH)

Background: Ramucirumab (RAM), a human IgG1 monoclonal antibody, inhibits ligand activation of VEGFR2. REACH and REACH-2 were two global, randomized, double-blind, placebo (PBO)-controlled multicenter, phase 3 studies of RAM vs PBO in patients with HCC after prior sorafenib. REACH-2 was designed to confirm the ramucirumab treatment benefit for patients with baseline AFP ≥400 ng/mL first observed in the prespecified subgroup of patients in REACH with AFP ≥400 ng/mL. The primary endpoint of REACH-2 was met demonstrating an improved overall survival (OS) compared to PBO, a result consistent with that in patients with AFP ≥400 ng/mL in REACH. Pooled analyses of patients from REACH-2 and REACH with baseline AFP ≥400 ng/mL was performed.

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LBA-003Withdrawn

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LBA-005KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer

Background: Pembrolizumab showed promising antitumor activity and a manageable safety profile in patients with pretreated G/GEJ cancer in KEYNOTE-012 and KEYNOTE-059. KEYNOTE-061 (NCT02370498) was a global, open-label phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemotherapy containing platinum and fluoropyrimidine.

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Author Index

Abada, Paolo   LBA-001

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P-200Risk factors of colorectal cancer in Linxian, China: A nutrition intervention trial with 30 years follow-up

Introduction: Colorectal cancer (CRC) is one of the most common cancers in the world. Epidemiological and experimental studies have shown that some dietary factors and vitamins/minerals are associated with the risk of CRC. The Nutrition Intervention Trial (NIT) tested whether daily multivitamin/mineral supplements could reduce the incidence and mortality rate of esophageal/gastric cardia cancer. The current study evaluated the CRC risk factors at the NIT population.

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P-233Trifluridine/tipiracil vs regorafenib as salvage-line treatment in patients with metastatic colorectal cancer: A multicenter retrospective study

Introduction: Trifluridine/tipiracil (TAS-102) and Regorafenib (REG) have shown promising activity in patients with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this study was to compare the efficacy and safety of TAS-102 and REG alone in patients with mCRC refractory to standard chemotherapies.

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P-267The prognostic impact of sidedness in RAS wild-type colorectal cancer

Introduction: Colorectal cancer (CRC) is a heterogeneous disease and sidedness [right colon (RC) vs. left colon (LC)] reflects different clinical, biological and molecular behaviors, which could have a significant prognostic impact. This study tried to evaluate the impact of sidedness on overall survival (OS) and progression-free survival (PFS) in RAS wild-type (RAS-WT) CRC patients treated with anti-EGFR antibodies in first line palliative chemotherapy.

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PD-008Molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital RNA counting

Introduction: Alterations in the mismatch repair (MMR) mechanism in colorectal cancers (CRCs) lead to high levels of microsatellite instability (MSI-h) causing considerable endogenous immune anti-tumor response, counterbalanced by immune inhibitory signals. We evaluated the mRNA immune-profile of a series of MSI-h CRCs to identify new potential targets for future CRC immunotherapy trials by combining an extensive gene expression analysis and the clinicopathological characteristics such as presence of metastases, staging, genotype and primary tumor sidedness.

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P-300Predictive value of circulating tumor-derived DNA (ctDNA) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CT-RT): Preliminary results

Introduction: In patients with LARC, neoadjuvant CT-RT followed by curative surgery is the standard of care. Risk-adopted treatment is based on MRI-predicting local T and N stage, radial margins and vascular involvement while no molecular predictive markers are available. In the present prospective study, we investigated the predictive role of serum ctDNA in patients with LARC.

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P-217ABCG2 and TOP-1 as predictive biomarkers and targets for therapy in colon cancer

Introduction: There is a need for new and innovative solutions in the medical treatment of colon cancer since many of these patients eventually develop resistance to currently used drugs leading to untreatable cancer disease and death of the patients. We have by using our DEN50-R cell line based screening platform (isogenic pairs of drug sensitive and drug resistant human cancer cell lines), followed by testing in the PETACC-3 prospective randomized clinical study, identified ABCG2 and TOP1 mRNA expression as significant predictive biomarkers for irinotecan (a topoisomerase 1 inhibitor) resistance in the adjuvant treatment of colon cancer. Moreover, we have identified a new drug (SCO-101) that reverses irinotecan resistance in preclinical experiments (the DEN50-R platform). Here we present the clinical data with the biomarkers and data on SCO-101 including the clinical development plans for the drug.

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P-251The prognostic ad predictive value of primary tumor sidedness in the mCRC pts

Introduction: The prognostic and predictive value of primary tumor sidedness in the pts with metastatic colorectal cancer (mCRC) is well known today. Right-sided primary was associated with high mutational burden, microsatellite instability, worse prognosis, more BRAF mutation rates and poor anti-EGFR response. We aimed to investigate the effects of tumor sidedness on survival, RAS-RAF mutation rates and responses to biologic agents in the pts with mCRC.

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P-284Characteristics of colorectal cancer in the elderly patients about 60 cases

Introduction: Older people constitute a heterogeneous population, according to World Health Organization, the elderly person is defined as any individual with a chronological age equal to or higher than 60 years. In most cases, colorectal carcinoma is a disease of the elderly. Occurs mostly in the elderly people of more than 65 years and it poses public health problem. For several years geriatric evaluation has shown multiple benefits and we are witnessing a significant improvement in the oncological management of these patients.

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P-316Is there any association of dose received by pelvic bone marrow in preoperative radiotherapy in rectal cancer with hematological toxicity of subsequent oxaliplatin-based chemotherapy?

Introduction: Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the association between irradiated volume of PBM and the tolerance of subsequent FOLFOX-4 chemotherapy in rectal cancer.

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WITHDRAWN

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O-001Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors

Introduction: TAS-120, an oral and highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor, has demonstrated inhibition of cancer cell growth in human xenografts of tumors bearing FGFR aberrations. TAS-120 inhibited mutant and wild-type FGFR2 with similar IC50 (wild-type FGFR2, 0.9 nM; V5651, 1-3 nM; N550H, 3.6 nM; E566G, 2.4 nM) and has shown efficacy in cell lines with acquired resistance to FGFR inhibitors. In this Phase I study in patients with advanced solid tumors, TAS-120 was evaluated at 8-24 mg once daily (QD). 20 mg QD was determined as the maximum tolerated dose/recommended Phase II dose, while 24 mg QD had dose-limiting toxicity. Here we report results from cholangiocarcinoma (CCA) patients enrolled in this Phase I study.

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P-191Combined analysis of KRAS, NRAS, BRAF mutations and mismatch repair deficiency testing in Indian patients with metastatic colorectal carcinoma: A single centre experience

Introduction: Molecular evaluation of KRAS, NRAS and BRAF mutation has become an important part in colorectal carcinoma evaluation as their alterations determine the therapeutic response to anti-EGFR therapy and prognosis. MMR deficiency is important for identification of Lynch syndrome families and it has now become an important biomarker of response to immunotherapy in metastatic CRC. The aim of this study is to investigate the distribution of these mutations by tumor localization and to determine the prevalence of MMR deficiency in metastatic colorectal cancer.

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P-208Autophagy (A) related proteins evaluation represents an independent survival factor of colorectal cancer (CRC) patients (pts)

Introduction: A holds a bimodal role during carcinogenesis. Before tumorigenesis, A promotes normal cells survival and suppress carcinogenesis, while after cancer development A induces cancer cells survival. The aim of this study is to assess the impact of A related proteins in the survival of CRC pts.

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P-225The role of maintenance therapy in the first line treatment of metastatic colorectal cancer

Introduction: The first line of chemotherapy is decisive in the treatment of colorectal cancer. Choosing the right one allows you to increase PFS and improve long-term results. Surgical treatment and maintenance therapy (MT) increase PFS and OS, as they can be prescribed at any stage of treatment.

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