Pregnancy in Breast Cancer Survivors.

Safety of pregnancy occurring after breast cancer treatment has been studied largely, but it is still debatable. These studies have generally showed that overall and disease-free survival in breast cancer survivors with subsequent pregnancy is not less than those without future pregnancy . Also, breast cancer survivors treated with chemotherapy , radiation therapy, or both had no increased risk of congenital anomalies, single gene disorders, or chromosomal syndromes in their offspring. However, it appears that the incidence of preterm labor, low birth weight, and fetal anomalies is higher in these cases.These issues as well as safe time interval from breast cancer treatment to pregnancy , safe contraceptive method after breast cancer, counseling about pregnancy in survivors, and how to follow up the patient for breast cancer recurrence during pregnancy are discussed in this chapter.

Outcome Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Total Body Irradiation-Free Allogeneic Hematopoietic Stem Cell Transplantation: Comparison of Patients with and Without Central Nervous System Involvement.

Hematopoietic stem cell transplantation (HSCT) with a non-total body irradiation (TBI) conditioning regimen has proven feasible for treating patients with acute lymphoblastic leukemia (ALL). However, it is commonly believed that for extramedullary involvement of ALL in sanctuary sites, such as the central nervous system (CNS), TBI shall not be abandoned. In this study, the outcomes of pediatric ALL patients with CNS involvement (CNS+) and without CNS involvement (CNS-) treated with TBI-free allogeneic HSCT were retrospectively compared. The patients received a TBI-free busulfan plus cyclophosphamide conditioning regimen. Comparing CNS+ (n = 27) and CNS- (n = 134) patients, the 5-year probabilities of relapse (44.4% versus 41.8%; P = .799), disease-free survival (DFS; 48.1% versus 43.3%; P = .642) and overall survival (OS; 51.9% versus 47.0%; P = .646) were not significantly different. Although transplantation-related mortality (TRM) was higher in the CNS- patients, the difference between the 2 groups was not significant (3.7% versus 12.7%; P = .177). In multivariate analysis, there were no significant between-group differences in OS (P = .502), DFS (P = .424), relapse rate (P = .226), or TRM (P = .117). These findings suggest that HSCT using a non-TBI-containing conditioning regimen can lead to similar outcomes in pediatric ALL patients with and without CNS involvement. TBI-free allogeneic HSCT might be feasible and effective for CNS+ ALL patients.

Celecoxib Versus Diclofenac in Mild to Moderate Depression Management Among Breast Cancer Patients: A Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Depression is a well-known complication of breast cancer, which is known to adversely affect quality of life, prognosis, and survival in breast cancer patients. Celecoxib, a nonsteroidal anti-inflammatory drug, which acts via the selective inhibition of cyclo-oxygenase (COX)-2, has been shown to have antidepressive effects. OBJECTIVES: Here, we aimed to compare the efficacy and safety of celecoxib, a selective inhibitor of COX-2, with diclofenac, a nonselective inhibitor of both COX-1 and COX-2 in reducing depressive symptoms and pain in breast cancer patients. METHODS: A total of 52 outpatients with breast cancer with mild to moderate depression, who suffered from pain and needed analgesics, participated in the trial and underwent 6 weeks of treatment with either celecoxib (200 mg twice daily) or diclofenac (50 mg twice daily). Participants were investigated using the Hamilton Depression Rating Scale (HDRS). The primary outcome measure was to compare the antidepressant effects of celecoxib and diclofenac. RESULTS: Repeated-measures analysis demonstrated significant effect for Time × Treatment interaction on the HDRS scores: F(1.76, 87.85) = 9.66; P < 0.001. By study conclusion, greater improvement was observed in the HDRS score of the celecoxib group compared with the diclofenac group (P = 0.002). No one experienced remission (HDRS ≤ 7) in either group. Frequencies of adverse events were not significantly different between groups. CONCLUSION: Celecoxib seems to possess superior antidepressive effects compared with diclofenac in breast cancer patients with mild to moderate depression.

Evaluation of Immunohistochemical Expression of Survivin and its Correlation with qRT-PCR Results as a Useful Diagnostic Marker in Gastric Cancer.

Background: Today, survivin is known as one of the most specific cancer proteins; provide unique and practical study opportunities. Clinical value of survivin in gastric cancer (GC) is not yet appointed. To establish the expression level of survivin and its diagnosis value in Iranian patients with GC, we evaluated the association of survivin expression with clinicopathologic factors. Methods: Overall, 60 matched-normal controls with 60 GC samples including 30 cases with evidence of metastasis at time of our study and 30 cases without evidence of metastasis were recruited, in Tehran, Iran during 2008 to 2018. Survivin expression was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) study. Results: Increased expression of survivin at mRNA and protein levels was found in 86.7% and 71.6% of cases, respectively. Evidence indicated a significant difference in survivin mRNA expression level between tumor and nontumoral (marginal) tissues (P<0.001). The difference in expression of survivin mRNA was not significant between metastatic and non-metastatic tumor tissues (P=0.171). Positive immunoreactivity of survivin was observed to be predominantly in the nucleus of tumor cells. A significant difference in survivin protein expression was detected between tumor and non-tumoral tissues (P<0.001) and between metastatic and non-metastatic tumor tissues (P<0.001). There was no significant association between survivin mRNA expression and clinicopathological variables. However, survivin protein expression was significantly correlated with perineural involvement (P<0.018). Conclusion: This data could be supportive of using survivin as a useful diagnostic marker in GC. Although, more research is needed in this area.

Comparative Study of the Effects of Duloxetine and Venlafaxine on Acute Symptomatic Taxane-induced Neuropathy in Breast Cancer Patients: A Randomized Clinical Trial.

Introduction: Chemotherapeutic agents have the potential to induce neurotoxicity, resulting in a range of symptoms, including mild paresthesia, neuropathic pain, pronounced ataxia, and significant impairment. Taxane-induced neuropathy (TIN) is a prevalent adverse effect and a significant constraint of Taxane-based chemotherapy protocols in treating breast cancer. In this current study, we aim to compare the effects of Venlafaxine and Duloxetine in taxane-induced Neuropathy as well as the quality of life, Depression, and Anxiety in Breast cancer Patients. Methods: The present study investigated breast cancer patients who experienced acute neuropathic pain after receiving paclitaxel treatment, a chemotherapeutic agent. The participants were allocated randomly into two groups, one receiving Venlafaxine and the other receiving Duloxetine. The participants underwent assessments for anxiety, depression, pain, neuropathy, quality of life, and neuropathic pain through the administration of questionnaires at the commencement of the study and after ten weeks following the intervention. Results: Both groups exhibited decreased neuropathic pain, with the venlafaxine group significantly reducing McGill's pain score. Although, the result is not suggestive of a difference between venlafaxine and duloxetine impact on any variables scores. Conclusion: Duloxetine and Venlafaxine effectively treat neuropathic symptoms such as paraesthesia, tingling, and itching. Venlafaxine is also beneficial for relieving pain associated with neuropathy.This trial was retrospectively registered on 1.1.2023 at irct.ir (trial registration ID: IRCT20220115053723N1). URL: https://www.irct.ir/trial/62540/pdf.

Evaluation and Comparison of Citalopram and Venlafaxine for Management of Hot Flashes in Women with Breast Cancer.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Premature menopause and hot flashes are the main complications of breast cancer treatments. About 40 to 50 percent of breast cancer women who undergo chemotherapy are experiencing premature menopause symptoms, including hot flashes. Some endocrine therapies such as tamoxifen and aromatase inhibitors are associated with induction or aggravating hot flashes. Hot flashes are often debilitating and significantly impair daily functions. Therefore many therapeutic options have been studied so far for the management of this adverse effect. However, there are still some clinical challenges in managing hot flashes in patients with breast cancer. OBJECTIVE: We aimed to evaluate and compare the efficacy of venlafaxine and citalopram on hot flashes in breast cancer women receiving tamoxifen. DESIGN: We conducted a double-blind, placebo-controlled trial in forty-one, 35 to 65 years old female patients. The study lasted for four weeks, and the follow-up was for two months. Venlafaxine and citalopram treatments started with doses of 37.5 mg or 10 mg, respectively. Venlafaxine and citalopram dosages were increased in the second week to 75 and 20 mg, respectively. The study was conducted during the year 2017. KEY RESULTS: The results indicated that the total efficacy was significantly different in groups receiving citalopram, venlafaxine, and placebo. Total efficacy in the placebo group, venlafaxine, and citalopram was 14.3, 53.8, and 64.3%, respectively (p=0.02). During the second week, the efficacy in groups receiving citalopram, venlafaxine, and placebo was 57.1, 53.8, and 14.3%, respectively (p=0.04). Generally, both citalopram and venlafaxine were well tolerated. The associated adverse effects were mild to moderate in both groups. CONCLUSIONS: Although citalopram was associated with more adverse effects, including constipation, it was more effective in reducing the frequency of hot flashes when compared to venlafaxine or placebo.

Prognostic Factors of the Primary Central Nervous System Lymphoma: Clinical Experience from a Tertiary Care Center in the Middle East.

Aim Primary central nervous system lymphoma (PCNSL) is a rare extra nodal non-Hodgkin's lymphoma. The optimal treatment for PCNSL is still unclear. In this study, we present our experience with management of PCNSL in a tertiary care center in Iran. Methods In this retrospective study, 58 patients with tissue diagnosis of PCNSL were studied. All patients were treated with chemotherapy including intravenous high-dose methotrexate, rituximab and temozolomide and radiotherapy by the same oncologist. Statistical analysis was performed using SPSS. Results The mean overall survival (OS) in this study was 37.4 ± 13.6 months and the mean progression free survival (PFS) was 35.1 ± 9.8 months. The mean time to progression was 15.2 ± 8.79 months among 8 patients who experienced progression in this series. Finding of a positive CSF cytology was not linked with disease progression, while HIV infection and multifocal involvement at initial presentation were strongly linked to a lower PFS. The single most important factor affecting the OS was the histopathologic type of the PCNSL; two of the three patients who died from their disease in this series had non-B cell PCNSL, whereas only one patient with DLBCL died because of brainstem involvement. Conclusion The results of this study show a lower rate of HIV-infection in patients with PCNSL as compared to the series from the western countries. Non-B cell histopathology and HIV-infection were found to be associated with the dismal prognosis.

High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer.

Background: Microsatellite instability (MSI) is considered a key factor in carcinogenesis and a genetic alteration pattern in many types of cancers such as gastric cancer (GC). Although the role of MSI in colorectal cancer (CRC) is well known, its prognostic impact on GC has not been clearly defined. The assessment of MSI in GC has not been documented in the Iranian population yet. Therefore, this study analyzed the association of MSI status with GC in Iranian patients. Materials and Methods: We compared the frequency of MSI at 5 loci from formalin-fixed paraffin-embedded (FFPE) gastrectomy specimens, between metastatic and non-metastatic cases of GC (N = 60). A panel of five quasi-monomorphic markers and a single dinucleotide marker with linker-based fluorescent primers was used. Results: MSI was observed in 46.6% of cases, including MSI-high (H) (33.3%) and MSI-Low (L) (13.3%). Moreover, the most unstable and stable markers in our study were NR-21 and BAT-26 accordingly. MSI-H and MSI were seen more frequently in non-metastatic tumors (p= 0.028 and p= 0.019, respectively). Conclusion: The current study showed MSI status more frequently in non-metastatic GC which may reflect a good prognostic factor in GC like CRC. Although, larger and more comprehensive studies are needed to confirm this statement. A panel consisting of NR-21, BAT-25, and NR-27 mononucleotide markers appears to be reliable and useful markers for detecting MSI in GC in Iranian patients.

Association between Perceived Stress and Neutropenia in Patients with Leukemia under Chemotherapy.

Background: The most prominent part of the cellular response of the immune system is driven by neutrophils. These cells tend to decline following chemotherapy in patients with leukemia. Neutropenia is an influential factor in the prognosis of cancer patients. Stress reduces white blood cells (WBCs) and neutrophils are linked to an increased risk of infectious diseases after chemotherapy. We investigated the association between neutropenia and perceived stress following chemotherapy. Materials and Methods: We performed a cross-sectional study on 60 patients with leukemia in a university hospital. Participants completed self-report measures, including the demographic data and perceived stress scale (PSS) questionnaire. We compared rates of neutropenia, as a measure of chemotherapy prognosis, 10 days after chemotherapy in different stress levels. Moreover, the number of patients with polymorphonuclear (PMN) under 1000/microliter was compared at different stress levels.    Results: We found that neutropenia is directly correlated with negative stress perception and inversely correlated with positive stress perception. These effects appear more prominent in patients with PMN under 1000/microliter as the number of these patients was significantly more in groups with higher negative stress and less in groups with higher positive stress scores. Conclusion: It can be concluded that stress is correlated with neutropenia, and stress management in patients with leukemia will be accompanied by better recovery outcomes and reduced risk of infectious disease.

Comparison of Long-Acting G-CSF (PD-Lasta) with Short-Acting G-CSF (PD-Grastim) in Neutrophil Recovery Following Consolidation Chemotherapy with High-Dose Cytarabine in Acute Myeloid Leukemia: A Randomized Clinical Trial.

Background: Acute myeloid leukemia (AML) patients are often neutropenic as a result of their disease alone or following their chemotherapy. In this randomized clinical trial the efficacy of Iranian short-acting (PD-Grastim) and long-acting G-CSF (PD-Lasta) were compared in term of time to recovery from neutropenia in de novo AML patients following the consolidation chemotherapy. Materials and Methods: Patients (n = 51) received one or two courses of Cytarabine and Daunorubicin as an induction. If complete remission was achieved, the treatment was followed by high-dose Cytarabine as consolidation chemotherapy. Twenty- four hours after the consolidation chemotherapy, patient were randomized to receive either daily short-acting G-CSF (PD-Grastim) (300 µg/kg) or single-dose long-acting G-CSF (PD-Lasta) (6 mg). Results: The median time to recovery of neutrophils was 11.00 and 13.00 days for short-acting G-CSF (PD-Grastim) (n=22) and long-acting G-CSF (PD-Lasta) (n=29) groups, respectively (U=186.5, P>0.05 two-tailed). Incidence of adverse effects was similar in both short-acting G-CSF (PD-Grastim) and long-acting G-CSF (PD-Lasta) groups. Conclusion: Overall, data show that Iranian long-acting G-CSF (PD-Lasta) was not significantly different with Iranian short-acting G-CSF (PD-Grastim).

Primary diffuse large B-cell lymphoma of the bone mimicking osteomyelitis.

Consider primary bone lymphoma as an important differential diagnosis of osteomyelitis.In patients who are unresponsive to antibiotics and core needle biopsy result is incoherent with clinical symptoms, consider open biopsy for accurate diagnosis.

Pancreatic Neuroendocrine Tumor presenting as a diffuse pancreatic enlargement, case report and review of literature.

Pancreatic neuroendocrine tumors are rare neoplasms that comprise 1-2% of all pancreatic tumors. However, they are the second most common solid pancreatic neoplasms. They have a wide range of imaging appearances and they can show common to very rare imaging presentations. Most of the time they are solitary well-marginated enhancing solid mass arising in a certain aspect of the pancreas. We present a case report of a 41-year-old female who underwent clinical work-up for abdominal pain, loss of appetite and weight loss for the past year. Ultrasound, computed tomography, and magnetic resonance imaging show diffuse homogenous pancreatic enlargement without contour deformity or a focal mass. Lymphoma and autoimmune pancreatitis were suggested based on imaging findings but IGg4 level and other lab data were normal. Endoscopic ultrasonography confirmed the diffuse enlargement of the pancreas without peripheral structures involvement. The pathological results of multiple fine-needle aspiration biopsy from all parts of the enlarged pancreas revealed a low-grade neuroendocrine tumor.

Comparing the Effects of Melatonin and Zolpidem on Sleep Quality, Depression, and Anxiety in PatientsWithColorectalCancerUndergoingChemotherapy.

INTRODUCTION: Patients with cancer may have many complications involving their psychosomatic systems, such as sleep disturbance, depression, and anxiety. Thus, many research studies were conducted to reduce these complications. Zolpidem, as a short-term non-benzodiazepine treatment of insomnia, and melatonin as a chronobiological functionregulatory hormone, are commonly used for improving sleep quality. This randomized clinical trial aims to compare the effects of zolpidem and melatonin on sleep quality, depression, and anxiety in patients with colorectal cancer. METHODS: In this single-blinded trial, 90 patients with colorectal cancer undergoing chemotherapy who had obtained a score of 5 or higher on the Pittsburgh Sleep Quality Index (PSQI) were randomly divided into two groups (n=45). One group was treated with 10 mg zolpidem at bedtime, and the other group received 6 mg melatonin at bedtime for 30 days. PSQI on weeks 0, 4, 8, Groningen sleep quality scale, Hamilton rating scale for depression, and Hamilton anxiety rating scale questionnaires were performed to assess patients on weeks 0, 4, and 8. The outcome was then analyzed, and P≤0.05 was considered statistically significant. RESULTS: Both zolpidem and melatonin had significant impacts on sleep quality in week 4 (P<0.05). After stopping the treatments, the conditions were noticeably reversed on week 8 (P<0.05). Zolpidem and melatonin were relatively similar in affecting sleep duration, latency, efficiency, and disturbance. None of the two study medications had any considerable influence on anxiety and depression. CONCLUSION: Melatonin and zolpidem are promising agents for treating sleep complications and, to some extent, depression, and anxiety in cancer patients, according to the present study. However, further clinical trials are recommended to confirm the results of this study.

Evaluation of the Preventive Effects of Carvedilol on Trastuzumab-Induced Cardiotoxicity in Early-Stage and Locally Advanced HER2-Positive Breast Cancer Patients.

Background: Trastuzumab is an efficient monoclonal antibody used in the treatment of Her2-positive breast cancer. Despite its prominent effect on Her2-positive patients' disease-free Survival. Trastuzumab-induced cardiotoxicity is still one of the main challenges. Angiotensin-converting enzyme inhibitors (ACE inhibitors) are one of the most potent agents used in heart failure, which also showed confirmed cardioprotective effects against anthracycline and doxorubicin. We aimed to assess the cardioprotective effects of Carvedilol in a randomized clinical trial study. Materials and Methods: sixty non-metastatic Her-2 positive patients (30 cases; 30 controls) were entered into the study via a simple randomization method.Carvedilol was administered for the patients with the starting dose of 3.125 mg twice a day and started 7 days before trastuzumab administration. The dose has been increased in a three-week period to reach 12.5 mg twice a day and continued until the end of therapy. All the patients underwent an echocardiography after receiving Adriamycin and Cyclophosphamide in order to measure basal Ejection Fraction (EF) and Pulmonary Artery Pressure (PAP). Each patient underwent a follow-up echocardiography in 3,6,9 and 12 months after initiation of the treatment. Finally, all the patients went through the last episode of echocardiography 1 month after the end of treatment. All the Measured PAP and EF has been recorded and analyzed Results: EF and PAP changes for both groups had no significant changes during the course of treatment with Trastuzmab (p-value = 0.628 and p-value = 0.723, respectively). Seven patients in the intervention group and 2 patients in the control group presented with EF decrease. Also, 8 patients in the intervention and 9 patients in the control groups showed PAP increase. Conclusion: According to our results, in patients with HER2-positive breast cancer treated with trastuzumab, Carvedilol showed no significant protective effect on trastuzumab-induced cardiotoxicity.

Radiation-Free myeloablative allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia: A comparison of outcomes between patients with and without central nervous system involvement.

For patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), total body irradiation (TBI) has been particularly advocated as a part of the conditioning regimen in case of extramedullary involvement in sanctuary sites such as the central nervous system (CNS), to ensure greater tissue penetration. In resource-limited countries lacking TBI facilities; however, ALL patients undergo radiation-free myeloablative conditioning, though its impacts on post-HSCT outcomes of the patients with pre-HSCT CNS involvement have not been analyzed. In this 14-year series of 278 adult (> 18 y) ALL patients undergoing TBI-free busulfan/cyclophosphamide conditioning allo-HSCT, we found that the long-term probabilities of overall survival, disease free survival, relapse and non-relapse mortality were not significantly different between CNS-involved and CNS-spared patients. Moreover, there was no statistically significant difference in the incidence of post-HSCT CNS relapse between CNS-involved and CNS-spared patients. Pre-HSCT cranial radiation therapy (CRT) showed no significant preventive effect on the likelihood of post-HSCT CNS relapse. Through multivariable regression analysis, grade III-IV acute graft-versus-host disease (GvHD), extensive chronic GvHD and post-HSCT relapse were ascertained as independent determinants of mortality (Adj.R2 = 53.9 %, F(12,265) = 28.1, P < 0.001), while other parameters including Philadelphia translocation, pre-HSCT CNS involvement and CRT were found to have no independent effect. Although this study was not an attempt to compare TBI-based vs. non-TBI conditioning, the TBI-free myeloablative allo-HSCT was shown to be feasible and an option for adult ALL patients with CNS involvement, considering the comparable outcomes between patients with and without CNS involvement.

Henna-induced Hemolysis and Acute Kidney Injury in an 85-year-old Man; a Case Report.

Henna is a commonly used traditional cosmetic agent, which also holds medical potentials and is used to treat skin lesions including seborrheic dermatitis or fungal infections and also has possible anti-inflammatory effects. It contains lawsone (2-hydroxy-1,4-naphthoquinone) and, therefore, has the potential to induce oxidative hemolysis. Henna-induced hemolysis has been previously reported in children with Glucose 6-Phosphate Dehydrogenase Deficiency. Here, we report an 85-year-old man who developed hemolytic anemia and acute kidney injury following oral consumption of henna to help his dyspnea. He was treated with hydration, bicarbonate, and dexamethasone. Over the course of hospitalization, the patient developed ventilator-associated pneumonia and was treated with antibiotic. He was discharged after one month. This finding is of high importance due to common use of henna, especially among people with false beliefs regarding traditional and herbal medicine, and highlights the role of a full history taking.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FINDINGS: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. IMPLICATIONS: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.