Neoadjuvant Chemotherapy in Patients with HER2-Negative Breast Cancer: A Report from Clinical Breast Cancer Registry of Iran.

BACKGROUND: Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens. METHODS: A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC). RESULTS: Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates. CONCLUSION: This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates.

Evaluation of Serum Vitamin B12 Levels in Patients with Colon and Breast Cancer: A Case-Control Study.

Background: It has been shown that increased serum levels of vitamin B12 may be associated with some malignancies. This study aimed to compare the serum levels of vitamin B12 in patients with colon and breast cancer and healthy individuals. Materials and Methods: In this case-control study, 140 patients with colon and breast cancer were compared with 140 healthy individuals matched in age, gender, and socioeconomic status. Serum levels of vitamin B12 were measured through the Electrochemiluminescence method in both groups. The normal serum level of vitamin B12 was between 200 and 800 pg/ml. Results: Among 280 enrolled subjects, 60 had serum vitamin B12 levels higher than 800 pg/ml. Forty-six (32.9%) patients had high serum vitamin B12 levels, compared to 14 (10.0%) subjects in the control group (P = 0.001). The mean serum vitamin B12 level was significantly higher in the patients (380.4 ±540.2 pg/ml vs. 278.0 ±314.08 pg/ml, P =0.001). There was no statistically significant difference in serum levels of vitamin B12 in patients with breast and colon tumors (P = 0.8). A significant positive correlation was observed between serum levels of vitamin B12 and tumor stage (P = 0.001, r = 0.49). Conclusion: The findings of this study showed that serum levels of vitamin B12 in patients with colon and breast cancer are higher than in healthy individuals and are positively associated with the stages of cancer.

Effectiveness of adjuvant chemotherapy in patients with Stage II colorectal cancer: A multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy (ACT) for patients with Stage II colorectal cancer (CRC) is an area of controversy in oncology. International guidelines recommend the use of ACT in patients with specific high-risk features. This study aimed to investigate the effectiveness of ACT in improving survival in patients with and without high-risk features. MATERIALS AND METHODS: A total of 225 patients with Stage II CRC who underwent primary tumor resection were included in this study. Patients with one or more high-risk features including T4 tumor, poor differentiation, lymphovascular invasion, perineural invasion, bowel obstruction, local perforation, positive resection margins, or suboptimal lymph node sampling (fewer than 12 nodes) were classified as high risk. The survival analysis was performed between patients who only received curative surgery and those received single-agent (5-fluorouracil [5-FU] and leucovorin [LV] or capecitabine) or multiagent ACT (oxaliplatin and 5-FU + LV or oxaliplatin and capecitabine). RESULTS: The 5-year overall survival (OS) rate was 88.4%, and the 5-year disease-free survival (DFS) rate was 80.4%. The 5-year OS and DFS rates improved insignificantly with ACT (89.8% vs. 81.2%, P = 0.59 and 81.3% vs. 74.6%, P = 0.41, respectively); however, multiagent ACT results to inferior 5-year OS and DFS compared to single-agent ACT (82.1 vs. 92.8%, P = 0.14 and 70.1% vs. 86%, P = 0.07, respectively). ACT was associated with insignificant improved OS and DFS in both high-risk and low-risk groups, but high-risk patients who received multiagent ACT had a significant inferior OS and DFS in comparison with those received single-agent ACT. T4 tumor and obstruction were independent poor prognostic factors affecting OS and DFS. CONCLUSION: In our population, the improvement of OS and DFS with ACT was not statistically significant in high-risk and low-risk patients with Stage II CRC.

Sixteen Years of Experience with the Treatment of Advanced Colorectal Cancer in Iran; A Report from Three Institutions.

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide. Recently treatments of advanced CRC have been immensely improved. In this study we reported the current state of advanced CRC in Iran regarding treatment and outcomes from 2000 to 2016. METHODS 370 subjects with stage III or IV of the disease were included in this study. Pathological subtypes other than adenocarcinoma were excluded. Demographics and other relevant clinical data were collected. RESULTS Mean age at diagnosis was 55.4 ± 12.6 years. Significant differences regarding the age, sex, primary tumor complication and location, lymph node involvement, and tumor size were not detected between patients with stage III and IV. Overall survival rate at 5 years was 69.5% (95% confidence interval: 60.8% - 76.6%) and 21.73% (95% CI: 12.46% - 32.70%) for patients with stage III and IV, respectively. Analysis of prognostic factors revealed that tumor grade was an independent factor predicting poorer outcome (poorly differentiated vs. well or moderately differentiated). Furthermore, in stage IV of the disease, IVb subgroup was found to be associated with a poorer outcome compared with stage IVa. CONCLUSION Even with the acceptable survival rates and more effective treatments, it seems that clinicopathological characteristics have yet the most important prognostic effect in advanced CRC.

Association Study of HLA-DQB1*0602 Allele in Iranian Patients with Narcolepsy.

Narcolepsy is a rare, disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. Several studies demonstrated its association with HLA-DQB1*0602 in various ethnic groups. Our study aimed to determine the prevalence of HLA-DQB1*0602 allele in Iranian patients with narcolepsy and assess its predictive parameters for diagnosing narcolepsy. In addition, car accidents and job problems were assessed among narcoleptic patients. We studied 44 narcoleptic patients, 30 patients with other types of excessive daytime sleepiness (EDS)  and 50 healthy age and sex matched individuals in this case-control study. Patients and controls filled out a questionnaire including items about car accidents due to sleepiness and job problems. International classification of sleep disorders-2 criteria was used as the gold standard for diagnosis of narcolepsy. The DNAs isolated from whole blood samples were collected from the patients and controls to assess the presence of HLA-DQB1*0602. The results showed that HLA DQB1*0602 was present in 4 (8%) individual of controls and 20 (45.5%) patients with higher prevalence in patients with cataplexy (78.9%) than patients without cataplexy (p<0.001). The sensitivities of the DQB1*0602 for diagnosing narcolepsy with cataplexy and narcolepsy without cataplexy were 78.9 and 20; specificities were 88 and 72.4, respectively. 18.2% of patients had car accidents due to sleepiness and 68.2% suffered from job problems. Our study shows that evaluation of DQB1*0602 in patients suspected to narcolepsy could be helpful especially in complex cases with atypical cataplexy and indistinguishable multiple sleep latency test MSLT results. Moreover, high rates of car accidents and job problems are found among narcoleptic patients.

Melatonin therapy in shift workers with difficulty falling asleep: A randomized, double-blind, placebo-controlled crossover field study.

BACKGROUND: Disturbed sleep is common in shift work. It is hypothesized that administration of exogenous melatonin could reduce the sleep latency and improve the sleep quality. OBJECTIVE: To evaluate the efficacy of 3 mg melatonin taken 30 min before night time sleep on shift workers with difficulty falling asleep. METHODS: Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were applied to find out shift workers with difficulty falling asleep. A randomized, double-blind, placebo-controlled crossover study with periods of 3 night and washouts of 2 weeks comparing melatonin with placebo was performed. Night time sleep parameters obtained from somnowatch including total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE) and wakening after sleep onset (WASO) were analyzed. RESULTS: Among 295 workers, 103 had difficulty falling asleep. Finally, from 50 randomly selected workers with difficulty falling asleep, 39 workers completed the study. Melatonin treatment significantly increased SE and decreased SOL in comparison with baseline and taking placebo. SE was increased from 82.1% at baseline to 85.5% after melatonin therapy. Also SOL was decreased from 0.27 h at baseline to 0.20 h after melatonin therapy. Effects of Melatonin administration on TST and WASO were not significant. CONCLUSIONS: This study showed that melatonin therapy in shift workers with difficulty falling asleep significantly improved the sleep onset latency and sleep efficiency.

Immunosuppressive therapy in patients with aplastic anemia: a single-center retrospective study.

BACKGROUND: Aplastic anemia (AA) is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy. METHODS: Patients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA) were treated with cyclosporine (CsA) and danazol while patients with severe AA (SAA) as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol. RESULTS: Among the 63 studied patients, 29 (46%) had NSAA and 34 (54%) had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01). The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment. CONCLUSION: This long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.

The STOP-BANG questionnaire: reliability and validity of the Persian version in sleep clinic population.

PURPOSE: The snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, gender (STOP-BANG) is a concise and effective obstructive sleep apnea (OSA) screening tool, part questionnaire (STOP), and part demographic or anthropometric measurements (BANG). The main purpose of this study was to translate this well-liked questionnaire into Persian and assess its reliability and validity in sleep clinic population. METHODS: Standard forward-backward method was used for translation. A sample of 603 patients, who admitted to the sleep clinic, completely answered to the STOP questionnaire and underwent in-laboratory polysomnography, included in this study. Height, weight, and neck circumference were measured by technicians for calculating BANG score. The apnea-hypopnea index (AHI) on the polysomnography was used as gold standard for OSA diagnosis: none (AHI < 5), mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30). One hundred and forty one patients were answered to the STOP questionnaire twice at a time interval of 2-4 weeks for test-retest analysis. RESULTS: In reliability analysis, 124 (87.9 %) patients had same STOP score and 130 (92.2 %) patients were classified in same risk of OSA. Based on the polysomnography, 438 patients (72.6 %) had mild (n = 124, 20.4 %), moderate (n = 114, 18.9 %), and severe (n = 201, 33.3 %) OSA, whereas according to the STOP-BANG, 502 patients (83.3 %) were at high risk of OSA. The sensitivity and specificity of the STOP-BANG were found to be 91.6 and 45.2 %, respectively, at AHI ≥ 5, 97.1 and 35.2 %, respectively, at AHI ≥ 15, and 98 and 29.4 %, respectively, at AHI ≥ 30. The area under the curve of the STOP-BANG for identifying mild, moderate, and severe OSA was 0.805, 0.779, and 0.755, respectively. CONCLUSIONS: Persian version of the STOP-BANG performs similar to its original version and is an easy-to-use questionnaire which could be considered as a reliable and valid tool for OSA screening.

The Epworth Sleepiness Scale for screening of the drowsy driving: comparison with the maintenance of wakefulness test in an Iranian sample of commercial drivers.

Traffic fatalities are a major cause of morbidity and mortality in Iran. Occupational sleep medicine field needs more cost-effective and applicable tests for screening purposes. This study reports on a pilot screening study for drowsy drivers in an urban Iranian sample of commercial drivers. The Maintenance of Wakefulness Test (MWT) measures the ability to remain awake objectively. Sleep latency in MWT is a reasonable predictor of driving simulator performance in drivers. In this study, we evaluate whether the Epworth Sleepiness Scale (ESS) and MWT are equally useful in drivers with possible Excessive Daytime Sleepiness (EDS). 46 consecutive road truck drivers in a transportation terminal entered into this study. The ESS score of patients with normal and abnormal MWT was 3.24±2.4 and 4.08±3 respectively which was not significantly differenced (P value = 0.34). No significant correlation was found between the ESS and sleep latency in MWT (r=-0.28, 95%CI= -0.58 to 0.02). By using the receiver operating characteristic analysis, the area under the curve was found to be 0.57 (95% confidence interval = 0.37- 0.77) which is not statistically acceptable (P value=0.46). Our finding showed that the MWT and ESS do not measure the same parameter.

The Insomnia Severity Index: cross-cultural adaptation and psychometric evaluation of a Persian version.

PURPOSE: The main purpose of this study was to describe the cultural adaptation of a Persian version of the Insomnia Severity Index and to evaluate its psychometric properties by testing internal consistency, construct validity, discriminant validity, and concurrent validity. METHODS: Cross-cultural adaptation was carried out according to guidelines and included forward and backward translations, expert committee, and field test. A sample of 1,037 sleep clinic patients filled in a questionnaire package including the Persian version of the Insomnia Severity Index (ISI-P), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Beck Depression Inventory (BDI). In addition, 624 of these patients were assessed by polysomnography (PSG). A group of 50 members of hospital staff responded to the ISI-P as the control group. Internal consistency with Cronbach's alpha, construct validity with principal component analysis, discriminant validity with assessing the ISI-P's ability to differentiate patients from control group and concurrent validity with exploring the spearman correlation with the PSQI, ESS, BDI, and corresponding parameters in PSG were followed to examine the psychometric properties of the ISI-P. RESULTS: The ISI-P showed acceptable internal consistency (Cronbach's alpha = 0.78) and a 2-factor solution in factor analysis. The ISI-P discriminated well between patients and control group (15.90 ± 6.12 vs 10.10 ± 5.76, P value <0.001). Items and total score of the ISI-P showed a weak correlation with the corresponding parameters in PSG. The ISI-P total score was significantly correlated with total score of the PSQI (r = 0.74, P value <0.001) and the BDI (r = 0.42, P value <0.001), while it was not significantly correlated with total score of the ESS (r = 0.12, P value = 0.72). CONCLUSIONS: Cross-cultural adaptation was successful, and the ISI-P has good psychometric properties. Using the ISI-P is recommended to evaluate insomnia in research and clinical settings in Persian-speaking people.

The Epworth Sleepiness Scale: translation and validation study of the Iranian version.

PURPOSE: The main purpose of this study was to assess the reliability and validity of the Iranian version of the Epworth Sleepiness Scale (ESS-IR). METHODS: This was a cross-sectional study of 507 suspicious patients either to obstructive sleep apnea (n = 466) or narcolepsy (n = 41) in order to carry out a psychometric evaluation of the ESS-IR by performing reliability, validity, and responsiveness analyses. Reliability of the ESS-IR was assessed by internal consistency and test-retest reliability. Validity of the instrument was assessed using several statistical approaches including construct validity (exploratory factor analysis), discriminant validity, and criterion validity. Responsiveness of the ESS-IR was assessed by comparing the ESS-IR total score before and after 6-9 months of continues positive airway pressure (CPAP) treatment in 16 patients with obstructive sleep apnea (OSA). RESULTS: The ESS-IR had an acceptable internal consistency and test-retest reliability. Factor analysis in both groups showed a two-factor solution for the ESS-IR, but the first factor showed statistically significant loads in all items. In addition, the ESS-IR discriminated well between patients with and without OSA. There is a fair correlation between the ESS-IR total score and multiple sleep latency test results that is not significant at all. Finally, the ESS-IR was found to be responsive to change where the total score was significantly decreased after CPAP treatment (P < 0.001). CONCLUSION: The findings suggest that the ESS-IR is a reliable and valid measure for evaluating daytime sleepiness and now can be used in research and clinical settings in Iran.