Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

Background and purpose:

Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.

n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p <0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients. 

In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p< 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 ± 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 ± 4.36) in months, (95% CI: 35.218-52.330) (p< 0.05).

IDO-1 expression is an in­de­pendent prognostic biomarker to predict 
OS and progression in HGG. IDO-1 can be evaluated as an alternative instrument for precision medicine in the treatment of gliomas.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Treatment approaches for managing patients with hematological malignancies in the time of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is a unique challenge to the care of patients with hematological malignancies. We aim to provide supportive guidance to clinicians making individual patients decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. DISCUSSION: This review also provides recommendations, which are convenient in evaluating indications for therapy, reducing therapy-associated immunosuppression, and reducing healthcare utilization in patients with specific hematological malignancies in the COVID-19 era. Specific decisions regarding treatment of hematological malignancies will need to be individualized, based on disease risk, risk of immunosuppression, rates of community transmission of SARS-CoV-2, and available local healthcare resources.

A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma?

INTRODUCTION: The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line. MATERIAL AND METHODS: It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels. RESULTS: It was observed that increased anti-apoptosis genes, such as CASP2, CASP7, DDFA, and BCL2, anti-apoptotic gene, reduced APAF1, CASP8. Proliferation induced through while increased ADAMTS1, CDH1, CDH6, CLDN7, CSF3, MMP7, MMP13 genes. Autophagy increased via increasing MAP1LC3B, ATG-16L1 genes while decreased via suppressed ULK1, and ATG7 genes by silencing FBLN1 with siRNAs (p < 0.05). CONCLUSIONS: Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.

Herpes simplex encephalitis and pseudotumour cerebri due to isotretinoin.

Isotretinoin can have significant adverse reactions on multiple systems. We report a unique case of pseudotumour cerebri and herpes encephalitis resulting due to isotretinoin. A 19-year-old female patient was admitted to our clinic, presenting with headache, nausea, vomiting and fever since three days. She had used isotretinoin for the last two months. The patient's neurological examination revealed the presence of neck stiffnes and a body temperature of 39,0◦C. MRI showed high signal localized to the temporal lobe and insula on the right and widened cerebrospinal fluid signal intensity on either side of the optic nerve. Electroencephalogram sharp and wave paroxysms on the right temporo-parietal region. Lumbar puncture showed an opening pressure of 320 mm H2O. The cerebrospinal fluid displayed the presence of 4-5 lymphocytes. On these grounds, the diagnosis of pseudotumour cerebri and herpes encephalitis was made. It is thus suggested that the physicians must keep in mind that pseudotumour cerebri and herpes encephalitis are possible adverse effects of isotretinoin.

Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less.

The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P=0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4-29.6), and 8 months for CTx (95% confidence interval: 5.5-10.6) (P<0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P<0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P<0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade.

Predictive value of stathmin-1 and osteopontin expression for taxan resistance in metastatic castrate-resistant prostate cancer.

OBJECTIVE: Several pathways are known to be activated during metastasis and treatment of cancer. We investigated the role of osteopontin (OPN) and stathmin-1 (STHMN1) in metastatic castrate-resistant (mCRPC). METHODS: We included 30 patients who received at least 6 cycles of taxane regimen for metastatic mPC in the present study. For this study retrospective data was taken from Firat University, Faculty of Medicine, Medical Oncology Department between 2009 and 2015. OPN expression and STHMN1 expression were retrospectively evaluated by immunohistochemical staining in biopsy specimens. The relationship between the expression levels of OPN and STMN1 and the response to taxane based regimen and survival was analyzed. RESULTS: There was mild or strong overexpression of OPN and STHMN1 in all the patients. STHMN1 expression was mildly positive (+2) in four of the cases (13.2%) while it was strongly positive (+3) in 25 (83.4%) cases. Similarly, OPN expression was mildly positive (+2) and strongly positive (+3) in five (16.6%) and 25 (87.4%) patients, respectively. There was no significant correlation between the expression levels of STHMN1 and OPN, survival, and response to taxane based regimen (p>0.05); however, OPN overexpression showed a significant correlation with lower Gleason scores (GS) (p:0.032). CONCLUSIONS: STHMN1 and OPN may be prognostic markers although they are not predictive markers of response to treatment in mCRPC. The overexpression of OPN may help identifying patients with lower GS.

Osteonecrosis in the both femoral heads in a patient with Neuro-Behcet's Disease.

Neuro-Behçet's disease (NBD) is a rare clinical entity that frequently presents neuro-psychiatric symptoms, and mesodiencephalic and pontobulbar lesions. There is only one published report about osteonecrosis in NBD. We report a patient whose first presentation was neurological NBD with presenting bilateral femoral heads osteonecrosis. A 36-year-old male was hospitalized with gait disorder, diplopia and speech disorder. The past medical history of the patient was unremarkable. The MR image showed mesencephalic lesion with oedemaas a hyperintense area. The present case was diagnosed as NBD and treated with methylprednisolone (1g /day) only for five days. One year after, bilateral hip pain developed. MR image of both hips showed well-demarcated areas of osteonecrosis in the bilateral femoral heads. The patient was operated by an orthopedic surgeon. Because early diagnosis and immediate treatment of osteonecrosis is very important, the physician must bear in mind that osteonecrosis might result from impaired microvascular involvement in even NBD.

Evaluation of prognostic factors in localized high-grade undifferentiated pleomorphic sarcoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology.

Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19-90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6-30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2-160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision.

Retrospective multicenter evaluation of patients diagnosed with mucosal melanoma: a study of Anatolian Society of Medical Oncology.

Mucosal melanoma (MM) is a rare type of cancer that differs significantly from cutaneous melanoma. In this study, we aimed to evaluate clinical and demographical characteristics, prognoses and factors influencing survival, treatment alternatives, and features of different subtypes of the patients. The patients were followed up with and treated in different centers due to their diagnoses of MM. We retrospectively analyzed data of 107 patients who were diagnosed with MM in 14 different institutions in Turkey. The mean age of the patients was 64.5 years. Of the patients, 47 % were female and 53 % were male. The median overall survival (OS) was 17 months, and the mean follow-up duration was 27 months. The 2-year survival rate was 42 %, and the 5-year survival rate was 23 %. The best survival rate appeared in those patients with MM in the head-neck region (median survival rate was 27 months, P = 0.034). The most common anatomical site was the head-neck region. In a univariate analysis, variables including age ≥65 years, the anatomical site of the primary lesion other than head and neck region, the metastatic stage of the disease, high levels of lactate dehydrogenase (LDH), and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 were found to be associated with poor survival (P < 0.05). However, in a multivariate analysis, only advanced stage disease (HR = 2.70; 95 % CI, 1.64-4.45; P = 0.000) and high LDH levels (HR = 2.31; 95 % CI, 1.40-3.80; P = 0.001) were determined to be adverse prognostic variables. Primary MM presents a more aggressive behavior and offers a poorer prognosis compared to cutaneous melanoma. Because the disease is rarely seen, is heterogeneous, and lacks randomized studies, issues concerning optimal treatment approaches and management and clinical characteristics of the disease have not been clarified yet.

The effect of the gastrectomy on survival in patients with metastatic gastric cancer: a study of ASMO.

AIM: To investigate the role of surgical resection of primary tumor on overall survival (OS) in advanced gastric cancer patients at the time of diagnosis. PATIENTS & METHODS: The survival rates of metastatic gastric cancer patients whose gastric primary tumor was resected at time of diagnosis were compared with metastatic gastric cancer patients whose primary tumor was nonresected. RESULTS: The median progression-free survival and OS in operated and nonoperated group were 10 versus 6, 14 versus 9 months, respectively (p < 0.001). In multivariate analysis, gastric resection of primary tumor, Eastern Cooperative Oncology Group performance status, second-line chemotherapy had a significant effect on OS (hazard ratio [HR]: 0.52 [95% CI: 0.38-0.71], HR: 0.57 [95% CI: 0.42-0.78], HR: 1.48 [1.09-2.01]; p ≤ 0.001, p = 0.001 and p = 0.012, respectively). CONCLUSION: Subpopulations of patients with metastatic gastric cancer might benefit from surgical removal of primary tumor.

Unusual presentation; seeding of tumor after biopsy for hepatocellular carcinoma.

Hepatocellular cancer is one of the most common and fatal cancer tumor worldwide. However, the obtained results are questionable in terms of medical treatment of hepatocellular cancer. The muscle, soft tissue and cutaneous metastases of hepatocellular cancer, for instance, are rare and may result from interventional procedures. Seeding of tumor along the biopsy needle upon percutaneous biopsy is a very rare phenomenon. We report a very rare case of a 79 -year- old man, known to be hepatitis C virus carrier with a metastatic tumor in abdominal wall caused by seeding of tumor after three years following a percutaneous biopsy procedure. Even years later, after a biopsy procedure for diagnostic purposes and may be soft tissue metastases. This complication is a very rare condition that should not be ignored but can be observed. The biopsy requirement should be questioned closely and avoided unnecessary biopsy procedures.

Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology.

Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer.

Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.

Prognostic impact of tumor lymphocytic infiltrates in patients with breast cancer undergoing neoadjuvant chemotherapy.

PURPOSE: The presence of a pronounced tumor lymphocytic infiltrate (TLI) is deemed to reflect the presence of an immunoinflammatory response against the tumor and may thus have prognostic significance. We investigated the prognostic value of TLI detected in pathological specimens collected following neoadjuvant chemotherapy (NACT) in patients with breast cancer. METHODS: 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline-and/or taxane-containing NACT were enrolled. Specimens collected after NACT were scored with the 4-point Klintrup scoring criteria for the presence of TLI. RESULTS: 60 patients had low-grade TLI and 40 high-grade TLI. Comparison of the patient population according to low-grade vs high-grade TLI revealed statistically significant difference both in terms of disease-free survival (DFS) (log rank-4.28, p<0.05) and overall survival (OS) (log rank=3.96, p<0.05), with high-grade TLI patients showing a better prognosis. Multivariate Cox regression analysis identified postoperative tumor size and low-grade TLI as the two main independent adverse prognostic factors. CONCLUSION: High-grade TLI may interfer with tumor growth and can represent a favorable prognostic factor in women with breast cancer undergoing NACT.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

The knockdown of stathmin with si-RNA inhibits invasion of mesothelioma.

BACKGROUND: To investigate the mechanism of action of stathmin1 (STMN1) in mesothelioma (MSM) and whether it has any role in its treatment. METHODS: STMN1 expression was examined using immunohistochemistry in biopsy tissues taken from MSM patients. The relationships between the levels of STMN1 expression in the pathology preparations of MSM patients, and the clinicopathological characteristics of these patients, and their survival times were investigated. Transfection of STMN1-specific siRNA into SPC212 cells was compared to negative control siRNAs. The mRNA levels of genes that may play a role in invasion, apoptosis, and autophagy were evaluated by RT-PCR. RESULTS: The expression of STMN1 was shown to be high in MSM tissues (p < 0.05). It was found that the only independent predictor factor affecting the survival time of MSM patients was the disease stage (p < 0.05). STMN1 was significantly reduced after siRNA intervention (81.5%). STMN1 with specific siRNA has been shown to suppress invasion by reducing the mRNA levels of cadherin-6 (CDH6), fibroblast growth factor-8 (FGF8), hypoxia-inducible factor 1 (HIF1A), matrix metallopeptidase 1-2 (gelatinase A) (MMP1-2), and TIMP metallopeptidase inhibitor 2 (TIMP2), which are important markers for invasion. Although the expression of apoptosis and autophagy-related genes, caspase-2 (Casp2) and LC-3, was reduced by silencing STMN1 with specific siRNA in western blot analysis, this effect was not observed in PCR results. CONCLUSIONS: Immunohistochemical analysis of STMN1 may contribute to the differential diagnosis of MSM, and STMN1 may also be considered as a potential therapeutic target in the early invasive stage of MSM therapy.

The overexpression of cyclin D1 is a positive prognostic factor in advanced-stage breast carcinoma cases.

OBJECTIVE: Cyclin D1 (CDDN1) is a protein required for mitotic cell cycle progression through the G1 phase, as well as a regulatory component of the cyclin-dependent kinases CDK4 and CDK6. In this study, we wanted to evaluate the relationship between CDDN1 expression and clinicopathological features in breast cancer (BC) cases and whether CDDN1 could be used as a prognostic biomarker for BC cases. METHODS: A total of 70 cases, 30 cases each with limited and advanced-stage BC, and as the control group, 10 healthy breast tissue, without a cancer diagnosis, with examined for benign reasons (mammoplasty, breast reduction surgery, etc.) were included in this study. The pathological specimens from the cases were stained, immunohistochemically, and categorized as a "low" (L) group or a "high" (H) group for CDDN1 expression. The cases' clinicopathological features and survival rates were evaluated statistically, within a 95% of confidence interval, p<0.05, retrospectively. RESULTS: The median follow-up period of the cases was 48.00 (range, 6-150) months. CDDN1 expression was significantly higher in advanced-stage BC cases than in normal breast tissue and limited-stage BC cases. The median overall survival (OS) was 96 months (CI 95%: 67.74-117.59) in the H-CDDN1 group, compared to the L-CDDN1 group not reached, but there was no relation (p>0.05). CDDN1 overexpression was more prominent in low-grade advanced BC cases (p=0.004). The median OS of advanced-stage BC cases with Grade 1 was significantly longer than those with other grades (p=0.04). CONCLUSION: Our results suggest that CDDN1 expression can be used as a potentially appropriate positive prognostic biomarker for advanced-stage BC cases.