Outcomes of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone in Esophageal Squamous Cell Carcinoma Induction chemotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: There is still no definite conclusion regarding the effect of Induction Chemotherapy (IC) combined with concurrent Chemoradiotherapy (CRT). Thus this study was aimed to assess outcomes of IC followed By CRT versus CRT alone in Esophageal Squamous Cell Carcinoma (ESCC). METHODS: This multicenter retrospective study performed on 105 patients who underwent CRT and 73 patients who underwent IC+CRT, between January 2016 and December 2018. The primary endpoints were OS (from the date of treatment to the date of death or 3- years follow-Up). The toxicities of CRT were graded according to the National Cancer Institute Common Toxicity Criteria (version 3.0). RESULTS: one-year (73.8% vs. 53.2%) and 2-year (53.4% vs. 38.5%) OS rate of the IC+CRT group was significantly higher than that of the CRT group (p < 0.05). No statistically significant differences were observed between the IC+CRT group and the CRT group (31.5% vs. 27.4%) in terms of the 3-year OS rate (p > 0.05). In multivariate logistic regression, age<60 (OR: 1.48; CI 95% 1.02-1.97), clinical staging II (OR: 1.36; CI 95% 1.11-1.88), and the addition of IC (OR: 1.66; CI 95% 1.07-2.19) were independent prognostic factors that affected survival positively. CONCLUSION: Our data demonstrated that a combination of IC and CRT might be a promising treatment strategy to further improve OS in ESCC patients.

Resveratrol and tetrahydroisoquinoline effects on neutrophil sensitivity to NETosis formation in low-risk essential thrombocythemia patients.

INTRODUCTION: Recent studies scrutinize how NETosis (a unique cell death mechanism of neutrophil), impacts thrombosis patients with essential thrombocythemia (ET). This research evaluates the susceptibility of ET neutrophils to form NETs and tests two potential inhibitors, resveratrol (RSV) and tetrahydroisoquinoline (THIQ), in vitro. METHODS: Platelet-rich plasma from low-risk ET patients was used, along with neutrophils from both patients and controls. NET formation assays, with or without RSV and THIQ treatment after LPS stimulation, were conducted in a CO2 incubator. Evaluation included flow cytometry and fluorescence microscopy for NET formation and ELISA for TNFα, IL8, and vWF:Ag levels in patient and control plasma. RESULTS: Neutrophils from ET patients released more NETs than controls, confirmed by flow cytometry and fluorescence microscopy. Additionally, patients had significantly higher plasma levels of IL8 and TNFα compared to controls, while RSV was more effective than THIQ in reducing NETosis rates in these patients. CONCLUSIONS: In ET patients, a platelet counts over 1 million indicates the need for preventive treatment against thrombotic events. Similarly, in this study, RSV and THIQ significantly reduced the rate of NETosis in ET patients with higher platelet counts, and this role was more prominent in the case of the second inhibitor (RSV).

Early occurrence of acute myelomonocytic leukemia (M4/M5) after liver transplantation: a case report.

INTRODUCTION: Acute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant. CASE PRESENTATION: The patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization. CONCLUSION: Acute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.

The effects of synbiotics supplementation on reducing chemotherapy-induced side effects in women with breast cancer: a randomized placebo-controlled double-blind clinical trial.

BACKGROUND: The prevalence of breast cancer and its mortality rate are increasing rapidly among women worldwide. On other hand, the courses of chemotherapy as the main treatment for these patients are too much exhaustive and annoying. This study was designed to evaluate the use of synbiotics (probiotics + prebiotics) supplementation as a safe and inexpensive adjuvant treatment in reducing common chemotherapy side effects in women with breast cancer. METHODS: The current study was conducted on 67 women with definitive diagnosis of breast cancer who were hospitalized to receive one-day chemotherapy sessions, and met the inclusion criteria. The patients were randomly allocated to the intervention or control group to receive synbiotics or placebo, respectively. They received oral consumption of synbiotics supplements twice a day for 8 weeks. The primary outcome was the changes in severity or experience of chemotherapy complication, analyzed by intention to treat (ITT). The instruments included 7 validated questionnaires which were used to assess chemotherapy complications in the initiation, 4 weeks and 8 weeks after intervention. Dietary intake was measured by 24-h dietary recall at the beginning, week 4 and week 8. Data were analyzed by SPSS software version 24. P-value < 0.05 was considered as statistically significant. RESULTS: 67 breast cancer patients participated in the study. 8 weeks after intervention and adjusting the confounders, the severity of chemotherapy complications including unnormal defecation (P = 0.005) and fatigue (P < 0/001) decreased significantly in the synbiotics group compared to the placebo group. Furthermore, nausea/vomiting (P = 0.015), and anorexia (P < 0.001) were decreased at the end of the study compared to the first visit, but it was not statistically significant compared to the placebo group. CONCLUSIONS: Synbiotics supplementation during chemotherapy can potentially reduce the severity of fatigue and abnormal defecation. It can help reduce anorexia and nausea/vomiting. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) (registered code: IRCT20091114002709N56) (date of registration: 5/5/2021). Direct link to the trial page: https://www.irct.ir/trial/54559 .

Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study.

BACKGROUND: Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. METHODS: This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). CONCLUSION: Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.

Programmed Death 1 (PD-1) Expression in Relapsing and Remitting Hodgkin Lymphoma as Prognostic Factor.

BACKGROUND: Programmed death ligand 1 (PD-L1) plays critical role in PD-1-dependent immunity suppress. Abnormal PD-L1 expression has shown to be directly related to poor prognosis and drug resistance in cancer patients. Hence, we aimed to evaluate PD-L1 expression in relapsing and remitting Hodgkin lymphoma (HL) as a prognostic factor. METHODS: In this cross-sectional study, 100 patients with HL between 2007 and 2015, were included. A thin section of tumor tissue fixed and processed on slides, stained by immunohistochemistry (IHC) PD-L1 specific antibodies. The clinical, imaging and pathology information of patients were obtained using case reading and by retrospective follow-up. The status of recurrence or improvement was determined after 5 years of diagnosis. GraphPad Prism v.8 was used for analysis. RESULTS: of 100 HL cases, the mean age of 33 relapsed group cases was significantly higher than remission group (p-value = 0.006), and gender was not significant however majority of cases in both groups were male. The frequency of PD-L1 expression found in 49% of all patients. A significant relationship was found between the expression of PD-L1 and disease progression, HL subtype, stage of tumor (p-value<0.05). High expression of PD-L1 found in majority of relapse group and low expression in remission group. CONCLUSION: PD-L1 expression assessment in HL patients is a valuable tool for prediction of the disease subtype, progression, stage, and treatment outcome. IHC method as an available, simple, rather cheap, and efficient tool could use for evaluation of PD-L1 expression and predicting the prognosis of HL disease, elsewhere.

Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula in Crohn's Disease: Case Series Clinical Interventional Study.

Objective: Perianal fistulas in Crohn's disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD. Materials and Methods: This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points. Results: In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening. Conclusion: Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.

SARS-CoV-2 antibody response after BBIBP-CorV (Sinopharm) vaccination in cancer patients: A case-control study.

Background: Long-term safety and efficacy of BBIBP-CorV vaccine especially in individuals with chronic diseases, like cancer, is under investigation. In the present prospective study, we aimed to evaluate severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody response with BBIBP-CorV vaccine in Iranian cancer patients. Methods: All the patients registered to receive BBIBP-CorV (Sinopharm) vaccine were divided into two groups of with (cases = 107) and without (controls = 45) history of cancer. Serum levels of SARS-CoV anti-spike recombinant receptor binding domain (anti-sRBD) and anti-nucleocapsid (anti-N) IgG serum levels were measured on days 0 (phase 0), 28-32 (phase I), and 56-64 (phase II) of vaccination. The data were analyzed using SPSS, version 22. Results: Totally, 152 individuals (67.1% females) with the mean age of 46.71 ± 15.36 years were included. Solid cancers included 87.8% of the cancer cases (46.7% gynecological and 31.8% gastrointestinal cancer). At Phases I and II, positive anti-sRBD IgG and anti-N IgG were significantly lower among the cases in total analysis. Side effects were not significantly different between the cases and controls. The lowest positive anti-sRBD IgG test was observed among the cancer patients who were simultaneously receiving chemotherapy (35.3%). Anti-sRBD IgG and anti-N IgG serum levels significantly increased at phases I and II in total analysis and in each group. In addition, serum anti-sRBD IgG increased during the three phases and it was significantly higher in the control group. Conclusion: Full vaccination of COVID-19 by BBIBP-CorV in immunocompromised patients such as cancer patients is safe and effective and could induce antibody response but in lower levels compared to healthy people. Probable causes to have minor antibody response found in males, older ages, individuals with BMI ≥ 25, those without past history of COVID-19 and with hematologic cancers. No significant side effects after vaccination were seen.

Long Non-Coding RNAs Expression in Breast Cancer: CBR3-AS1 LncRNA as a Sensitive Biomarker.

BACKGROUND: Long non-coding RNAs (LncRNAs) are eminent genes in the human genome that interfere with the regulation of many complexities of organisms and control many of the various biological processes. As a result, it is considered that they may play an important role in different cancers. With regard to the high prevalence of breast cancer and the role of lncRNA, the present study aimed at investigating the expression of various lncRNAs. METHOD: Fresh tissues were obtained from operating rooms of Shariati, Khatamolanbia, and Milad Hospitals (Tehran, Iran) by a surgeon. A total of 45 tumor samples and 45 non-tumor samples (from the margin of tumor) were obtained from the same patients. Relative expression evaluation method was used in Real time PCR. Estrogenn receptor (ER), progesterone receptor (PR), and HER2 expression were analyzed using IHC analyses of each cell block. RESULTS: Participants included 44 female and 1 male with the mean age ± SD of 50 ± 12.0 years (range: 23-74). A majority of participants (41/45) were Ductal carcinoma type. Our results showed significant expressions for CBR3-AS1 (P-value=0.0139), RAB6C-AS1 (P-value=0.0023), and ZEB2-AS1 (P-value=0.0289) in comparison with the healthy cells. ROC curve analysis for CBR3-AS1 LncRNA revaled sensitivity more than 70%. CONCLUSION: Although CBR3-AS1, RAB6C-AS1, and ZEB2-AS1 lncRNAs were found to have high expressions in the breast cancer cells, only CBR3-AS1 lncRNA has a high chance to be a breast cancer biomarker.
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COVID19 Prevention & Care; A Cancer Specific Guideline.

On March 11th 2020, the coronavirus outbreak was declared a pandemic by the WHO. One of the groups that is considered high risk in this pandemic are cancer patients as they are treated with a variety of immune system suppressor treatment modalities and this puts them in a great risk for infectious disease (including COVID-19). Therefore, cancer patients require higher level measures for preventing and treating infectious diseases. furthermore, cancer patients may bear additional risk due to the restriction of access to the routine diagnostic and therapeutic services during such epidemic. Since most of the attention of health systems is towards patients affected with COVID-19, the need for structured and unified approaches to COVID-19 prevention and care specific to cancer patients and cancer centers is felt more than ever. This article provides the recommendations and possible actions that should be considered by patients, their caregivers and families, physician, nurses, managers and staff of medical centers involved in cancer diagnosis and treatment. We pursued two major goals in our recommendations: first, limiting the exposure of cancer patients to medical environments and second, modifying the treatment modalities in a manner that reduces the probability of myelosuppression such as delaying elective diagnostic and therapeutic services, shortening the treatment course, or prolonging the interval between treatment courses.

Left renal Ewing's sarcoma: A case study and a review of imaging literature.

Extra-skeletal Ewing's sarcoma is among the rarest tumors in adults. The primary sites of the tumor dictates symptoms and signs, thus early treatments are compromised when more common tumors are lined up as differentials by the location. We present a case of a 35-year-old pregnant female who developed a renal Ewing sarcoma during pregnancy. A prior simple left kidney cyst in an ultrasound with no tumor signs was spotted. A month after her cesarean section she visited a doctor when she was sent and admitted for surgery with renal cell carcinoma as the primary diagnosis to the Firoozgar hospital. Histology confirmed the final diagnosis. To this end, she completed the standard chemotherapy for the renal Ewing sarcoma with pulmonary metastasis when she was re-evaluated for the general bone pain, diagnosed with multiple bone metastases, and ultimately approached her palliative care. She expired after 2 months. This study demonstrates: a gently progressive mass; palpable in late stages; introduced rise in mean corpuscular volume and lactate dehydrogenase with no drop in the hematocrit. In conclusion, any random parenchymal and/or cortical thickening in primary ultrasound and/or computed tomography demonstrating a cyst-whether displaying internal echo or not- with suggested signs should be furtherly evaluated.

Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially serious adverse drug reaction that can result in lethal vascular thrombosis. Dabigatran is a direct thrombin inhibitor that might be useful in the management of HIT. This study evaluated the efficacy and safety of dabigatran in patients with HIT. We included 43 patients in the study who received dabigatran for the management of suspected HIT, based on 4Ts (thrombocytopenia, timing of platelet count drop, thrombosis or other sequelae, and other causes of thrombocytopenia) scores. Three patients were excluded because they had received dabigatran with a creatinine clearance <15 mL/min. Patients' records were analyzed longitudinally, with 12 months follow-up from the time of initiation of dabigatran, for occurrence of thrombosis, dabigatran-related complications, and outcome. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, active bleeding, and extremes of weights (<50 and >120 kg) were excluded from the study. Arterial thrombosis was not observed in any of our patients. The platelet counts normalized in all patients except for 2, which was attributed to the underlying comorbidities. We did not observe any hemorrhagic events or significant thrombosis during the follow-up period. Eight patients died from nonthrombotic causes, which were unrelated to adverse effects of dabigatran. Based on our findings, dabigatran could be considered a safe and effective agent in the management of HIT, particularly in the developing countries, where there could be issues with the cost and availability of other agents recommended for this condition. Further studies are needed to validate our findings.

Integration rates of human papilloma virus genome in a molecular survey on cervical specimens among Iranian patients.

The human papilloma virus (HPV) as a major causative agent of different cancers is under investigation globally. In this study, we aim to investigate HPV infection in different cytological and pathological stages by different molecular methods, and then the viral genome integration of HPV-16 and -18 is determined by a specific real-time PCR method. The study included women who underwent liquid-based cytology. HPV PCR was conducted by MY09/11 universal primers, HPV genotyping was performed by INNO-LiPA HPV genotyping assay, and the viral genome status was defined by two real-time PCR assays. The statistics were calculated by SPSS v.22 software. In 1668 women included in the study with mean age±std. deviation of 35.6±0.7, HPV was detected in 632 (38%) participants. Following genotyping analyses, 16 HPV types and 713 strains were detected. HPV-16 and HPV-18 from high-risk types and HPV-6 and HPV-11 from low-risk types were the dominant types. We found HPV-16 strains in mixed form (58.8%), and of the HPV-18 strains, the episomal form was prevalent (92.9%). The statistics revealed significant presence of HPV-6 and within normal limits cases; HPV-16 and atypical squamous cells of undetermined significance; HPV-33 as well as HPV-39 and low-grade squamous intraepithelial lesion; HPV-6 and atypical squamous cells of undetermined significance; and HPV-35 as well as HPV-56 and squamous cell carcinoma. Our study showed high prevalence of HPV in low-grade cervical lesions, although it is associated with higher grades. The HPV molecular testing extra to cytology is recommended. HPV-16 and HPV-18 have different programs in genome integration in infected cells.

Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinomas: A Single Center Study from Iran

Introduction: Lung cancer is the fifth leading tumor in Iran, and while its incidence remains relatively low, it has been increasing steadily. Targeted therapies have brought new hope to patients with non small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) gene is the prototype member of the type I receptor tyrosine kinase (TK) family and plays a pivotal role in cell proliferation and differentiation. Studies from Asian countries have revealed a higher frequency of EGFR mutations than in the West. The aim of this study was to measure the frequency and type of EGFR mutations in a group of Iranian patients with lung adenocarcinomas. Methods: Formalin fixed paraffin embedded (FFPE) lung adenocarcinoma tissues from 103 Iranian patients were sequentially tested for EGFR mutations by the polymerase chain reaction (PCR) followed by direct nucleotide sequencing of exons 18, 19, 20, and 21. Patient's demographics and other clinical details were obtained from the medical records of hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. Statistical analyses were performed with SPSS v.20. Results: EGFR mutations were detected in 25/103 (24.3%) patients. The most frequent was an exon 21 point mutation (L858R) (15 patients; 60%), followed by one in exon 19 (10 patients; 40%). The frequency of EGFR mutations in never-smoker patients was significantly higher than in smokers (68% versus 32%; p < 0. 01). Conclusion: EGFR mutation frequency is higher than in the West but lower than in East Asian and almost equal to reported rates for Indian and North African populations. Smoking is negatively associated with EGFR mutations in Iranian lung adenocarcinomas.

The Relationship between STR-PCR Chimerism Analysis and Chronic GvHD Following Hematopoietic Stem Cell Transplantation.

Background: The study attempts to assess the relationship between chimerism analysis using polymerase chain reaction of short tandem repeat (STR) and the incidence of chronic graft versus host disease (GvHD) as well as survival. Subjects and Methods: The retrospective cohort included all patients who received allo-HSCT during 2005-2013. Data collected by day +100 were reviewed in terms of the incidence of chronic GvHD and survival. Chimerism was evaluated for whole blood, T-cell and PMN cells on days 15, 30 and 60, respectively using polymerase chain reaction of short tandem repeat (STR). Results: Forty (69%) patients developed chronic GvHD, 11 (19%) relapsed and 22 (39.7%) expired during the study. There was a significant relationship between chronic GvHD and chimerism analysis including whole blood on day 60 (p=0.001), Polymorphonuclear neutrophil (PMN) on day 60 (p=0.05), T-cell on days 15 (p=0.028), 30 (p=0.01) and 60 (p=0.004). Patients with chronic GvHD showed a long-term survival as compared with those without chronic GvHD (p=0.0013). Conclusion: Conducting continuous analysis of chimerism provides an opportunity to initiate immediate measures in order to prevent complications.

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.

Chromogenic In Situ Hybridisation Test for Breast Cancer Patients with Equivocal IHC Results--a Study from Iran.

BACKGROUND: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. MATERIALS AND METHODS: This study was conducted from 2008- 2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. RESULTS: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. CONCLUSIONS: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders.

Occult HCV infection is a form of chronic HCV infection characterized by absence of detectable anti-HCV antibodies or plasma HCV-RNA but presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cells (PBMCs). The aim of this study was to determine the presence of HCV-RNA in PBMCs of patients with lymphoproliferative disorders. One hundred and four consecutive patients with lymphoproliferative disorders admitted to Firouzgar Hospital from January 2010 to March 2011 were recruited in this cross-sectional study. A 6-ml sample of whole blood was taken from the patients, the total RNA was extracted from the samples after the separation of plasma and PBMCs. The HCV-RNA of the samples was amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). The HCV genotypes of the positive samples were tested using the INNO-LiPA™ HCV II kit, and the HCV genotypes were then confirmed by sequencing of the 5'-UTR fragments after the PCR products were cloned into a pJET1.2/blunt cloning vector. The mean age of the patients was 48.3 ± 1.76 years (range: 16-83). HCV-RNA was found in PBMCs from 2 (1.9%) of the 104 patients. Genotyping showed that the patients were infected with HCV subtype 1a. One patient suffered non-Hodgkin's lymphoma and the other suffered chronic lymphocytic leukemia. Patients with lymphoproliferative disorders with negative anti-HCV antibodies and negative plasma HCV-RNA may have occult HCV infection. Therefore, in the absence of a liver biopsy, the testing of PBMCs for the detection of genomic HCV-RNA may be beneficial.

Comparing Efficacy of Preoperative neo-Adjuvant Chemotherapy and Surgery versus Surgery Alone in Patients with Resectable Gastroesophageal Cancer.

BACKGROUND: Recent researches have led to find strategies to prevent relapse and to improve survival for gastric cancer patients, including preoperative neo-adjuvant approaches. However, the efficacy of some neo-adjuvant regimens including 5-fluorouracil, cisplatin, and docetaxel have been less investigated. The present study evaluated the outcome and mid-term survival of patients with gastric cancer who undergoing this regimen. METHODS: In a randomized double-blinded controlled trial performed at the Firoozgar hospital in Tehran in 2011-12, 61 patients were randomly assigned to treatment (32 to neo-adjuvant chemotherapy with docetaxel, cisplatin and 5-fluorouracil (5-FU) before surgery and 27 to surgery alone). The present study tried to assess the efficacy of neoadjuvant chemotherapy regarding improvement of mid-term survival, complications, and R0 resection status. RESULTS: The two groups were matched in terms of gender, mean age, cancer location, and TNM staging. However, R0 resection in the former group was 85.7%; while this indicator in the isolated surgery group was significantly lower (61.5%). Regarding WHO performance, no significant difference was observed across the two groups. Patients in neo-adjuvant chemotherapy group were followed for mean follow-up time 10.32 months and those who categorized in isolated surgery group were followed for mean follow-up time 10.88 months. Mid-term mortality rate in the two groups was 14.3% and 15.4%, respectively (p = 0.866). In this regard, 3-, 6-, and 9-month survival rate in neo-adjuvant chemotherapy group was 96.4%, 89.3%, and 85.7%, respectively. These survival rates in the surgery group were 92.3%, 88.5%, and 84.6%, respectively. Multivariable logistic regression analysis showed that among all study variables, only R0 resection status could predict mid-term mortality. CONCLUSION: Neo-adjuvant chemotherapy and surgery compare to surgery alone more improve R0 resection status, but mid-term survival rate is similar in the two regiments. R0 resection status can effectively predict appropriate mid-term survival in undertreated patients.

Iranian hereditary hemochromatosis patients: baseline characteristics, laboratory data and gene mutations.

BACKGROUND: Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder in white people, characterized by highly abnormal uptake of iron from the gastrointestinal tracts. Recently, mutation studies have focused to detect the genes responsible for HH. MATERIAL/METHODS: In this cross-sectional study, 12 HH patients were recruited, who were referred to Firoozgar Hospital, Tehran, Iran. In addition to the clinical assessments, a complete laboratory evaluation, imaging modalities, histopathologic assessment, atomic absorption spectrophotometry and gene mutation study were performed. The genetic study for HFE gene mutation was examined for all of the patients since 2006, while non-HFE mutation was conducted since December 2010 (only for 1 of them). RESULTS: Twelve patients were evaluated consisting of 11 men and 1 woman, with the mean age of 39.58±12.68 yr. The average of atomic iron loads was 13.25±4.83-fold higher than normal standards. Four patients had heterozygotic mutation of H63D (33.3%). There was no significant difference in either the iron load of liver (P=0.927) and heart (P=0.164) or serum concentration of ferritin (P=0.907) and TIBC (P=0.937) between the HFE-mutant and without HFE mutation HH cases. CONCLUSIONS: In contrast to other studies, C282Y mutation was not detected in any of our Iranian HH patients. Heterozygotic mutations of H63D (HFE) and TFR2 (non-HFE) genes were found to be more common in these patients. Similar to previous reports, these mutations were not found to be significantly associated with severity of presentation in HH patients.