Psychiatric comorbidities and quality of life in breast cancer patients undergoing radiation treatment: Risk and protective factors.

OBJECTIVE: The primary goal was to evaluate the prevalence of psychiatric comorbidities and changes in psychological distress levels among breast cancer patients receiving radiotherapy (RT). The secondary goal was to determine risk and protective factors for psychiatric comorbidities of these patients. METHODS: From June 2018 to November 2019, patients were recruited from the hospital, Department of Psychiatry. Patients completed baseline surveys after seeing their radiation oncologist and prior to the first treatment, which was scheduled to take place within 7 days (visit 1, baseline); visit 2 occurred within 7 days after RT completion, and visit 3 occurred at 6 weeks after RT completion. A total of 99 patients participated in the study at visit 1; 56 patients completed the study through visit 3. RESULTS: Although changes in psychiatric comorbidities and overall quality of life were observed in patients with breast cancer prior to, during, and after RT, the differences were not significant among visits. Patients diagnosed with psychiatric comorbidities after RT had exhibited risk factors at previous visits, including preexisting psychiatric comorbidities, functional deterioration, and more severe symptoms related to breast cancer. Based on the results, the psychological characteristics of optimism and resilience can be considered as protective factors for psychiatric comorbidities. CONCLUSIONS: The results suggest that early detection and follow-up of psychological distress and poor quality of life at the onset of RT are of paramount importance, and that psychosocial interventions to enhance protective factors (optimism and resilience) may be helpful.

Glucocorticoid Receptor Gene (NR3C1) Expression in the Pathogenesis of Depression in Cancer.

Background: This study aimed to compare the NR3C1 expression among cancer patients with major depressive disorder (cancer depression), cancer patients without major depressive disorder (cancer non-depression), and major depressive disorder patients without cancer (general depression), as a preliminary investigation of epigenetic changes in the glucocorticoid receptor gene. Methods: From May 2019 to November 2019, patients were recruited from the Department of Psychiatry, Cancer Center in Busan, Korea. For gene expression studies, primers were designed using the Primer3 web tool (http://frodo.wi.mit.edu/primer3), and amplification reactions were performed. Results: Expression levels of NR3C1 were lower in cancer depression and general depression than in cancer non-depression group. Given that we observed downregulation of the NR3C1 gene expression in depressive patients regardless of cancer status, it appears that methylation changes in NR3C1 may contribute to the pathophysiology of depression. Conclusion: The results of this study imply that the expression of NR3C1 may be decreased in major depressive disorder.

Phase II study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study.

BACKGROUND: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation. METHODS: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. RESULTS: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). CONCLUSION: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.

Validity and Reliability of Korean Version of Simplified Nutritional Appetite Questionnaire in Patients with Advanced Cancer: A Multicenter, Longitudinal Study.

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m2 (range, 15.6 to 39.6 kg/m2). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p < 0.001) and PG-SGA (r=-0.530, p < 0.001). A significant weight loss of > 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.

Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma.

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Clinical Features and Survival of Patients With Follicular Lymphoma in Korea.

BACKGROUND: The incidence of follicular lymphoma (FL) varies according to geographic location. It is the second most common non-Hodgkin lymphoma in Western countries but has a very low incidence in Asia. Thus, no representative data are available for FL. Therefore, we gathered our own data to build a foundation for FL research. PATIENTS AND METHODS: We collected a total of 343 patient records. The median age was 53 years, and the ratio of male to female patients was 1.4:1. Most patients received chemotherapy with or without rituximab. RESULTS: The incidence of grade 1 and 2 FL was 64.9% (n = 205) and of stage III and IV was 51.2% (n = 171). The grade tended to be higher and the stage to be lower compared with Western data. In the chemotherapy group, the complete response rate was 76.0%, and the partial response rate was 17.1%. The median follow-up duration was 38.1 months. The estimated 5- and 10-year progression-free survival and overall survival rates were 68.3% and 84.9% and 63.0% and 71.3%, respectively. CONCLUSION: We could not find definitive differences between our Korean data and the Western data, although we found some trends in the baseline characteristics. Therefore, we hope to develop an understanding of FL and perform more qualitative studies in the future.

Clinical Significance of Peroxisome Proliferator-Activated Receptor γ and TRAP220 in Patients with Operable Colorectal Cancer.

PURPOSE: The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARγ or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARγ and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARγ and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARγ positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARγ and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARγ and TRAP220 represents a biomarker for good prognosis in CRC patients.

Clinical features and treatment of collecting duct carcinoma of the kidney from the korean cancer study group genitourinary and gynecology cancer committee.

PURPOSE: Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis. MATERIALS AND METHODS: From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases. RESULTS: Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months. CONCLUSION: CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.

Predictive value of in vitro adenosine triphosphate-based chemotherapy response assay in advanced gastric cancer patients who received oral 5-Fluorouracil after curative resection.

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes.

PURPOSE: The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes. METHODS: Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m(2) of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes). RESULTS: The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade ≥3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred. CONCLUSION: These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.

Clinicopathologic significance of ERCC1, thymidylate synthase and glutathione S-transferase P1 expression for advanced gastric cancer patients receiving adjuvant 5-FU and cisplatin chemotherapy.

The objective of this study was to determine whether the expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase P1 (GSTP1) are predictive of clinical outcomes in advanced gastric cancer (AGC) patients receiving treatment with adjuvant 5-fluorouracil (5-FU) and cisplatin (FP) chemotherapy. One hundred forty nine patients were included in this study. ERCC1 and GSTP1 expression was correlated significantly with tumor size (p = 0.040, p = 0.018, respectively). Stage and positive lymph node ratio were associated independently with disease free survival (DFS) and overall survival (OS). Both ERCC1 and GSTP1 expression had a significant impact on OS (hazard ratio = 0.069, p = 0.021). TS expression was not related to DFS and OS.

A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate.

Imatinib mesylate (IM) is used to treat a wide range of diseases, including Philadelphia chromosome-positive chronic myeloid leukemia (CML), on account of its high tolerability and low incidence of minor adverse events. Hemorrhage is thought to be a rare complication of IM. Recently, IM has been associated with reduced α2-plasmin inhibitor and platelet dysfunction. We report here the case of a 33-year-old female patient with CML who experienced subdural hematoma after an incremental increase in IM dosage due to a loss of complete molecular response. This case indicates that physicians should be alert to this atypical cause of headache in patients taking high-dose IM.

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide.

BACKGROUND: A combination of busulfan (Bu) and cyclophosphamide (Cy) has been used as a standard myeloablative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). Recent studies postulate that fludarabine (Flu) is a less toxic substitute for Cy. METHODS: Forty-two patients who were diagnosed with acute leukemia or myelodysplastic syndrome and received BuFlu (n=17) or BuCy (n=25) from August, 1999 to July, 2009 at Dong-A University Medical Center were retrospectively analyzed. RESULTS: The median follow-up duration was 39.75 months. The BuFlu group showed a lower incidence of mucositis (P=0.005), but there was no significant intergroup difference in the time of engraftment, nausea/vomiting, acute/chronic graft-versus-host disease, hepatic veno-occlusive disease, or hemorrhagic cystitis. Moreover, the 2 groups showed no significant difference in the cumulative risk of relapse, event-free survival, or overall survival. CONCLUSION: BuFlu administration can be employed as a preparative regimen for allogeneic HSCT and shows efficacy and transplant-adverse effects comparable to those of BuCy. However, randomized prospective studies in more patients are warranted.

Adjuvant chemoradiation versus chemotherapy in completely resected advanced gastric cancer with D2 nodal dissection.

AIM: Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer. METHODS: Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5-fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP. RESULTS: A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow-up duration was 77.2 months (range 24-92.8 months). We did not find any difference in 3-year disease-free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5-year disease-free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B. CONCLUSION: We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy.

Clinicopathological significance of p53, hypoxia-inducible factor 1alpha, and vascular endothelial growth factor expression in colorectal cancer.

BACKGROUND: The principal objective of this study was to evaluate the prognostic significances of p53, hypoxia inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) expression in colorectal cancer. MATERIALS AND METHODS: The tumor tissues of 311 patients with colorectal carcinoma that had undergone potentially curative resections were immunohistochemically assessed using monoclonal antibodies against p53, HIF-1α, and VEGF. RESULTS: Positivity rates of p53, HIF-1α, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1α expression in tumor tissues was determined to be correlated significantly with the expression of VEGF (p=0.040), and depth of invasion (p=0.019). Multivariate analysis demonstrated that HIF-1α was independently associated with poor overall survival (p=0.002). CONCLUSION: HIF-1α expression is associated with VEGF expression and angiogenesis in colorectal carcinoma. Additionally, the expression of HIF-1α in tumor tissue is associated with angiogenesis and poor overall survival in patients with colorectal cancer.

Improvement of the WHO classification-based prognostic scoring system (WPSS) by including age for Korean patients with the myelodysplastic syndrome.

BACKGROUND: The aim of this study was to improve the predictive power of the WHO classification-based prognostic scoring system (WPSS) by including age in patients with the myelodysplastic syndrome (MDS). PATIENTS AND METHODS: 136 Korean patients with de novo MDS between 1995 and 2008 were evaluated retrospectively. All patients were reclassified according to WHO criteria. 114 patients were included in the final analysis. An individualized age-adapted scoring system was developed to improve the accuracy of prognosis of the WPSS. RESULTS: The WPSS was significantly associated with the prediction of survival and the leukemia-free survival. While the risk of a patient with the WPSS was best represented by the values 0 (very low), +1 (low), +2 (intermediate), +3 (high), and +4 (very high), these values were found to vary between -1.0 and 4.2 in the same patients when age was included as a factor. The WPSS may vary according to age, <55 or ≥55 years. The estimated difference in median survival was more prominent in the lower risk groups of the WPSS than in the higher-risk groups. CONCLUSION: In addition to the WPSS, age was found to significantly influence the prognosis of patients with MDS and provided a more individualized prognosis for the patients with MDS.

A case of 5-fluorouracil induced encephalopathy.

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m²) for 5 days and cisplatin (60 mg/m²) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.

Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer.

BACKGROUND: Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis. METHODS: A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry. RESULTS: Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (p = 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (p = 0.531, p = 0.701, respectively) and overall survival (p = 0.563, p = 0.572, respectively). Multivariate analysis showed that VEGF (p = 0.032), CEA (p = 0.012), lymph node metastasis (p = 0.002), and TNM stage (p = 0.025) were independently associated with overall survival. CONCLUSIONS: Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.

Clinical outcomes and breast cancer subtypes in patients with brain metastases.

BACKGROUND: The principal objective of this study was to assess clinical outcomes by breast cancer subtype in patients with brain metastases. METHODS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status was evaluated via immunohistochemical staining. Four survival time intervals were compared according to the subtype (ER+/HER2-, HER2+, triple negative (TN)). RESULTS: 20 (30.3%) of the 66 patients in this study were ER+/HER2-, 20 (30.3%) were HER2+, and 26 (39.4%) were TN. The disease-free survival rates of ER+/HER2-, HER2+, and TN patients were 30.0, 17.0, and 17.9 months, respectively (p = 0.040). The median time intervals from distant metastasis to brain metastasis were 20.6, 19.5, and 9.0 months, respectively (p = 0.012). The times from initial diagnosis to brain metastasis were 52.9, 33.6, and 25.5 months, respectively (p = 0.026). However, the overall survival rates did not differ significantly (p = 0.276). CONCLUSIONS: Patients with TN breast cancer were more likely to develop distant metastasis earlier, and also evidenced poor overall survival. Triple receptor status may be employed as a prognostic marker for breast cancer patients with brain metastases.

Clinicopathological significance of nuclear factor-kappa B, HIF-1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer.

Nuclear factor-kappaB (NF-kappaB), hypoxia-inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis, and metastases. The principal objective of this study was to assess the prognostic significance of NF-kappaB, HIF-1alpha, and VEGF expression in stage III colorectal cancer. Tumor tissues from 148 patients with stage III colorectal carcinoma, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-kappaB, HIF-1alpha, and VEGF. Positivity rates of NF-kappaB, HIF-1alpha, and VEGF were 47.3%, 42.6%, and 61.5%, respectively. NF-kappaB expression in tumor tissues was correlated significantly with HIF-1alpha expression (P < 0.001), VEGF expression (P = 0.044), and the presence of vascular invasion (P = 0.013). Univariate analysis demonstrated that NF-kappaB expression was associated with poor 5-year overall survival (55.8 months vs 76.9 months, P = 0.012). Multivariate analysis verified that NF-kappaB was independently associated with adverse outcomes (relative risk: 1.92, P = 0.049). However, HIF-1alpha and VEGF did not appear to be related to clinical outcomes. NF-kappaB expression in tumor tissue is associated with angiogenesis and poor 5-year overall survival in stage III colorectal cancer patients.