Preoperative neutrophil-to-lymphocyte ratio as a predictive factor for survival in nonmetastatic colorectal cancer.

BACKGROUND: The pretreatment ratio of neutrophils to lymphocytes (NLR) has been suggested as an indicator of poor outcome in various cancers. This study aimed to determine whether the preoperative NLR may be a predictor of survival in patients who underwent curative resection for colorectal cancer (CRC). MATERIALS AND METHODS: The records of 219 CRC patients underwent curative resection between 2008 and 2014 were retrospectively evaluated. NLR was calculated by preoperative complete blood counts. The effects of age, gender, anatomic location, histologic grade, lymphovascular invasion, pathological T, pathological N, and tumor-node-metastasis stages and NLR on disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate analyses. The optimal cutoff value for NLR was determined using receiver operating characteristic curve analysis. RESULTS: The best cutoff value of NLR was 2.8. Multivariate analysis showed that NLR was not a predictor of DFS. However, NLR was found as an independent prognostic factor for OS (Hazard ratio, 5.4; 95% confidence interval, 2.3-12.5; P = 0.0001). CONCLUSION: A preoperative NLR of more than 2.8 might be an independent predictor for OS in patients with CRC. This simple and routinely available laboratory parameter may be used as a useful marker for identifying patients with a worse prognosis.

What has changed in the clinical presentation of breast carcinoma in 15 years?

OBJECTIVE: The aim of this study is to investigate if there was a change in time in terms of age at diagnosis, menopausal status, pathologic tumor size, lymphatic metastasis and pathologic stage in patients with surgical treatment for breast carcinoma. MATERIAL AND METHODS: The clinical and pathological characteristics of 1223 patients with breast carcinoma who underwent surgical treatment between January 1994 and December 1998, and of 1346 patients who underwent surgical treatment with the same diagnosis between January 2004 and December 2008 were retrospectively reviewed. RESULTS: The median age at diagnosis was 48 (20-78) years during the first period, and 50 (20-91) years during the second period. While 27% of patients were 40 years of age or younger in the first period, this ratio decreased to 20% during the second period (p=0.0001). The rate of premenopausal patients was 54% in the first period and 46% in the second period (p=0.0001). The median tumor size at diagnosis was 3 cm at the first period, and 2.5 cm at the second period. The number of patients with tumor size ≤2 cm increased in time from 391 (32%) to 531 (39%) (p=0.0001). Among young patients (aged ≤40 years), the number of patients with tumor size 2 cm or smaller were 81 (24.5%) and 92 (33.8%) at the first and second periods, respectively (p=0.001). Lymphatic metastases rate of patients aged ≤40 years was higher than patients aged >40 years, in both study periods (p=0.0001). The number of patients staged as pN1 at the first period increased from 356 (50.8%) to 441 (56.3%) at the second interval, while those staged as pN3 decreased from 251 (35.8%) to 175 (22.3%) (p=0.0001). CONCLUSION: It may be concluded that recently, breast cancer is diagnosed at older ages, the rate of young and premenopausal patients and size on diagnosis has decreased, and breast-conserving surgery is used more often.

Adjuvant chemoradiation versus chemotherapy for stage III gastric cancer after surgery with curative intent.

OBJECTIVE: Gastric cancer is often diagnosed at an advanced stage and surgery alone cannot guarantee satisfactory results. Both chemoradiotherapy (CRT) and chemotherapy (CT) are used in postoperative therapy. However, it is controversial whether CRT or CT is better after D2 lymphadenectomy. In this study we investigated the efficacy of adjuvant CRT versus CT in stage III gastric cancer patients treated with R0 gastrectomy and D2 lymph node dissection. PATIENTS AND METHODS: Data from 92 patients diagnosed with gastric adenocarcinoma and treated with surgery followed by adjuvant treatment were retrospectively analyzed. Patients were classified into two groups depending on type of adjuvant treatment such as CT (Arm A) and CRT (Arm B). RESULTS: Twenty-one patients in Arm A and 71 patients in Arm B were included. Median age at diagnosis was 60 years. The median follow-up time was 30 months. No difference in local recurrence (14.3 vs 15.7%, P = 0.89), peritoneal recurrence (29.4 vs 23.5%, P = 0.62), and distant metastases rates (57.1 vs 45.1%, P = 0.42) were observed between the arms. Disease-free survival (DFS) rates did not differ between Arms A and B (26 and 22 months, P = 0.80) respectively. Median overall survival (OS) in Arm A was 29 months and it was 32 months for Arm B. There was no difference in 5-year OS and DFS between Arms A and B (23.8 vs 34.4%, P = 0.74; and 24.1 vs 32.9%, P = 0.80). CONCLUSIONS: Adjuvant CRT does not appear to improve clinical outcomes compared to adjuvant CT in this study and prospective studies are required to confirm these results.

Subtype is a predictive factor of nonsentinel lymph node involvement in sentinel node-positive breast cancer patients.

PURPOSE: This study aimed to identify the effect of breast cancer subtype on nonsentinel lymph node (NSLN) metastasis in patients with a positive sentinel lymph node (SLN). METHODS: The records of 104 early breast cancer patients with a positive SLN between April 2009 and September 2013 were retrospectively evaluated. All patients underwent axillary lymph node dissection. The effects of the tumor subtype (luminal A, luminal/HER2+, human epidermal growth factor receptor 2 [HER2] overexpression, and triple-negative) and other clinicopathological factors on NSLN metastasis were examined by univariate and multivariate statistical analyses. RESULTS: Fifty of 104 patients (48%) exhibited NSLN metastasis. Univariate and multivariate analyses revealed that tumor size and the ratio of positive SLNs were significant risk factors of NSLN metastasis in patients with a positive SLN. The rate of NSLN metastasis was higher in patients with luminal/HER2+ and HER2 overexpression subtypes than that in patients with other subtypes in the univariate analysis (p<0.001). In the multivariate analysis, both patients with luminal/HER2+ (p<0.006) and patients with HER2 overexpression (p<0.031) subtypes had a higher risk of NSLN metastasis than patients with the luminal A subtype. CONCLUSION: Subtype classification should be considered as an independent factor when evaluating the risk of NSLN metastasis in patients with a positive SLN. This result supports the development of new nomograms including breast cancer subtype to increase predictive accuracy.

The results of 21-year experience of treating anal squamous cell carcinomas.

OBJECTIVE: Anal squamous cell carcinomas are one of the rare cancer types. Due to the developments in the past 35 years, surgery is no longer the first treatment of choice. The aim of this study was to retrospectively examine the outcomes of 24 patients treated in a single center in the last 21 years in terms of applied treatment, local relapse, distant metastasis, post-treatment complications, and survival. MATERIAL AND METHODS: Data obtained from 24 anal squamous cell carcinoma patients, who were treated in Ankara Oncology Research and Education Hospital between 1990 and 2010, were retrospectively evaluated. RESULTS: Of the 24 patients, 16 had anal canal squamous cell carcinoma and eight had perianal squamous cell carcinoma. All of the patients with anal canal squamous cell carcinoma (n=16) received chemoradiotherapy. Three of these patients who did not respond to treatment, underwent abdominoperineal resection. The patients with perianal squamous cell tumors were treated by local excision. During the follow -ups, seven patients experienced local relapse, and one patient had distant organ metastasis. Only one patient died. Five-year disease free survival rate was found as 66%. CONCLUSION: Our findings suggest that the first alternative in the treatment of anal squamous cell tumors should be chemoradiotherapy; and surgery seems to be the appropriate approach for the non-responsive and relapsing cases.

Prognostic factors affecting postmastectomy locoregional recurrence in patients with early breast cancer: are intrinsic subtypes effective?

BACKGROUND: Many studies have investigated the association between the molecular subtypes of breast cancer and survival. The aim of this study was to identify the effects of intrinsic subtypes of breast cancer and the other clinicopathological factors on postmastectomy locoregional recurrence (LRR) in patients with early breast cancer. METHODS: The records of 1,195 consecutive early breast cancer patients treated with modified radical mastectomy between 2004 and 2008 were retrospectively evaluated. The effects of intrinsic subtypes of the tumor (luminal A, luminal B, HER2-overexpressing, and triple-negative) and classical clinicopathological factors on LRR were identified by univariate and multivariate statistical analyses. RESULTS: The median follow-up time was 44 months, and 16 (1.3%) patients experienced a LRR during this period. In univariate analysis, the intrinsic subtypes of breast cancer had a significant effect on LRR (p = 0.002). In multivariate analysis, only extranodal invasion and estrogen receptor (ER) status were significant predictors of LRR (p = 0.003 and 0.0001, respectively), whereas intrinsic subtypes did not reveal a significant relationship with LRR (p = 0.57; hazard ratio, 2.9; 95% confidence interval, 0.2-4.7). CONCLUSIONS: The results of this study suggest that the extranodal invasion and negative ER status should potentially be considered when evaluating the risk of LRR. The predictive power of intrinsic subtypes for LRR is less than that of classical pathological indicators. This information may be useful in planning management of LRR in early breast cancer patients treated with mastectomy.

Melatonin modulates the severity of taurocholate-induced acute pancreatitis in the rat.

The aim of this study was to investigate the effects of melatonin on serum amylase, tumor necrosis factor-alpha (TNF-alpha) and histological changes in rats with taurocholate-induced acute pancreatitis. Thirty male Wistar rats were randomly divided into three groups; group 1, group 2 and group 3 were enrolled as melatonin, control and sham groups, respectively (n = 10 per group). Acute pancreatitis was induced by 1 ml/kg body weight using 5% taurocholate injection into the biliopancreatic duct in groups 1 and 2 after clamping the hepatic duct. Those in group 1 received 50 mg/kg body weight melatonin by intraperitoneal (i.p.) injection. Group 2 received physiological saline i.p. at the same dose. Group 3 solely underwent laparotomy with cannulation of the biliopancreatic duct. Twenty-four hours after the intervention, the rats were killed, and serum samples were collected to measure amylase and TNF-alpha levels. Simultaneously, pancreatic tissues were removed, stained with hematoxylin-eosin and examined under a light microscope. Serum amylase and TNF-alpha levels were significantly lower in the melatonin group compared to the controls (P < 0.001). The total histological score, including edema, inflammation, perivascular infiltrate, acinar necrosis, fat necrosis and hemorrhage, was also significantly lower in the melatonin group as compared to the control (P < 0.0001). In conclusion, melatonin is potentially capable of reducing pancreatic damage by decreasing serum TNF-alpha levels in taurocholate-induced acute pancreatitis in rats. This result supports the idea that melatonin might be beneficial in ameliorating the severity of acute pancreatitis.

Triple negative phenotype and N-ratio are important for prognosis in patients with stage IIIB non-inflammatory breast carcinoma.

BACKGROUND AND OBJECTIVES: The aim is to evaluate novel prognostic factors such as triple negative (TN) phenotype and ratio between positive nodes and total dissected lymph nodes (N-ratio) in stage IIIB breast carcinoma patients. METHODS: In this retrospective study, primary endpoints were local recurrence (LR), distant recurrence (DR), and overall survival (OS). Univariate and multivariate prognostic factor analyses were carried out using Cox and Kaplan-Meier methods in the data of 185 patients. RESULTS: The median observation time was 36 (range 16-86) months. Pathological tumor size (continuous [cont.], P = 0.002; Hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1-1.3) and N-ratio (cont., P < 0.0001; HR, 1.02; CI, 1.01-1.03) were strongly associated with LR. Tumor phenotype (triple vs. non-triple, P = 0.002; HR, 2.6; CI, 1.4-4.7), N-ratio (cont., P = 0.01; HR, 1.02; CI, 1.01-1.03) and pathological tumor size (cont., P = 0.003; HR, 1.2; CI, 1.1-1.3) for DR, and also tumor phenotype (triple vs. non-triple, P < 0.0001; HR, 3.7; CI, 1.8-7.5), N-ratio (cont., P = 0.03; HR, 1.02; CI, 1.01-1.03) and pathological tumor size (cont., P = 0.006; HR, 1.3; CI, 1.2-1.4) for OS were the most important prognostic factors. CONCLUSIONS: N-Ratio and TN phenotype were the most important prognostic factors for stage IIIB breast carcinoma patients.

The selective inhibition of type IV phosphodiesterase attenuates the severity of the acute pancreatitis in rats.

Phosphodiesterases (PDEs) are enzymes primarily responsible for regulation of the intracellular cyclic nucleotides. Among these enzymes, the type 4 PDE is highly expressed in most immune and inflammatory cells and its inhibition causes the suppression of immune and inflammatory cell activity, including production of cytokines. This study was designed to investigate the efficacy of the type 4 PDE inhibitor rolipram on acute pancreatitis in rats. Rats were divided into three groups--treatment, control, and sham. In the treatment and control groups, rats were pretreated with rolipram and vehicle before acute pancreatitis was induced. The pretreatment of rats with rolipram significantly reduced the amylase (P<0.0001) and IL-1ß levels (P=0.002) compared to vehicle treated rats. Also, mean histopathological scores were significantly reduced by rolipram treatment (P<0.005). It can be concluded that rolipram ameliorates severity of pancreatitis in rats.

The prognostic importance of triple negative breast carcinoma.

There is a current debate on whether triple negative breast carcinomas (estrogen receptor--ER-negative, progesterone receptor--PR-negative and HER2-negative) have a poor prognosis. Our aim in this retrospective study was to determine whether triple negative feature is a prognostic factor for disease-free survival (DFS) in 322 breast carcinoma patients, of whom 80 (24.8%) had triple negative tumor histology. In the multivariate analysis, tumor subgroup (triple vs non-triple, p<0.0001; hazard ratio [HR], 4.2; 95% confidence interval [95%CI], 2.2-8.2) was a significant factor related to relapse, in addition to number of metastatic nodes (>4 vs

Incidental papillary microcarcinoma of the thyroid--factors affecting lymph node metastasis.

BACKGROUND AND AIMS: Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), these tumors are associated with lymph node metastasis. The aim of this study is to identify the rate of lymph node metastasis and evaluate the clinical and pathological factors affecting metastasis in thyroid PMC. METHODS: Among 475 patients with papillary thyroid carcinoma treated between 1990 and 2003, 81 patients (17%) were diagnosed as PMC and the records of these patients were evaluated retrospectively. Clinicopathologic features were evaluated by univariate and multivariate analyses. RESULTS: According to age, metastases, extent, and size risk definition, all patients were in low-risk group. Lymph node metastases were determined in 12.3% of patients. Mean follow-up was 7 years (range from 28 to 192 months). Ten-year disease-free and overall survival rates were 97 and 100%, respectively. Both multifocality and thyroid capsular invasion were found to be independent risk factors for lymph node metastasis by multivariate analysis. CONCLUSION: Patients with thyroid PMC in low-risk group with multifocal tumors and with capsule invasion may have increased risk of lymph node metastasis, and must be considered in follow-up of the patients who have these factors.

Prognostic factors affecting locoregional recurrence in patients with stage IIIB noninflammatory breast cancer.

BACKGROUND: The aim of the present study was to identify the clinicopathological factors affecting locoregional recurrence (LRR) in patients with clinical stage IIIB noninflammatory breast cancer (NIBC). METHODS: The records of 120 stage IIIB NIBC patients treated with neoadjuvant chemotherapy (NAC) and then modified radical mastectomy followed by radiotherapy were evaluated. In this retrospective cohort, the effects of age, menopausal status, clinical tumor size, clinical response to NAC, pathological axillary status, number of positive axillary lymph nodes, pathological response to NAC, grade, lymphovascular invasion, estrogen receptor status, progesterone receptor status, Her-2-neu status, and p53 status on LRR were evaluated by univariate and multivariate analyses. RESULTS: The clinical response rate of 120 patients was 79.2% (17.5% complete and 61.7% partial), with a complete pathological response rate of 12.5%. The median follow-up was 28 months (range: 10-74 months). The LRR rate was 13.3%. Based on the univariate analysis, the clinical tumor size, clinical response rate, pathological axillary status, four or more positive axillary lymph nodes, lymphovascular invasion, and estrogen receptor status were factors that significantly affected LRR. In the multivariate analysis, however, only the clinical response rate and the number of positive axillary lymph nodes were found to be statistically significant independent factors. CONCLUSIONS: Effective local control of disease can be achieved in patients with stage IIIB NIBC using a combination of NAC, surgery, and radiotherapy. However, a worse clinical response after chemotherapy and four or more positive axillary lymph nodes affect LRR negatively in these patients.

The correlation of extranodal invasion with other prognostic parameters in lymph node positive breast cancer.

BACKGROUND: The presence of extranodal invasion (ENI) in the metastatic lymph nodes is reported to increase the risk of locoregional recurrence while shortening disease-free and overall survival in patients with breast cancer. In this study the relationship between ENI and other prognostic parameters and survival is investigated. METHODS: Of 650 patients with breast cancer who were treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368 (56.6%) had lymph node metastasis. The patients with axillary metastasis were separated into two groups as with and without invasion to lymph node capsule and the surrounding adipose tissue. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. RESULTS: Of 368 patients with axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were found to be related with ENI. In the group with ENI, 5-year overall survival rate was 74.8%, compared to 82.3% for patients without ENI which was significantly lower (P = 0.04). CONCLUSIONS: In lymph node positive breast cancer with presence of ENI, adverse prognostic parameters are more frequently encountered and has a worse overall survival compared to group without ENI.

Prognostic factors for sporadic medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid carcinoma (MTC) originates from the thyroid parafollicular cells and accounts for 3% to 10% of all thyroid malignancies. Approximately 84% of cases are sporadic. The aim of this study was to evaluate the outcomes of treatment for sporadic medullary thyroid carcinoma (SMTC) and define the prognostic factors for overall survival. METHODS: The records of 32 SMTC patients treated at Ankara Oncology Education and Research Hospital between September 1993 and April 2003 were retrospectively evaluated. The effects of age, gender, tumor localization, extent of the primary surgical resection, tumor size, capsule invasion, lymph node metastasis, extranodal extension, tumor stage, local recurrence, and distant metastasis on the overall survival rate were evaluated by univariate and multivariate analyses. RESULTS: There were 32 patients (19 females, 13 males) with a median age of 45 years (21-76 years). Altogether, 22 patients had undergone complete resection and 10 patients incomplete resection. The median follow-up was 48 months (9-111 months), and the overall 5-year survival rate was 51%. Based on the univariate analysis, the extent of primary surgical resection, pathologic tumor size, capsule invasion, lymph node invasion, extranodal extension, tumor stage, local recurrence, and distant metastasis were factors that significantly affected survival. In the multivariate analysis, however, only the extent of the primary surgical resection, capsule invasion, and distant metastasis were found to be statistically significant factors. CONCLUSIONS: The extent of the primary surgical resection significantly influences the survival of patients with SMTC. Capsule invasion and distant metastasis were additional factors affecting the prognosis.

Prediction of survival in gastric carcinoma related to lymph node grading by the new American Joint Committee on Cancer/Union International Contre le Cancer System or the Japanese system.

OBJECTIVE: To compare the classification of gastric cancer adopted by the American Joint Committee on Cancer and the Union International contre le Cancer (AJCC/UICC) (number of nodes involved) with the Japanese classification (sites of nodes involved). DESIGN: Retrospective study. SETTING: Teaching hospital, Turkey. SUBJECTS: 134 consecutive patients whose gastric cancer was treated by D2 resection. INTERVENTIONS: Kaplan-Meier survival analysis and Cox's regression model. MAIN OUTCOME MEASURE: Accuracy of prognosis. RESULTS: There were no significant differences in survival rates when pN1 and pN2 categories of the AJCC/UICC classification were subdivided into the n1 and n2 categories of the Japanese classification. However, when those in the n1 and n2 categories of the Japanese classification were subdivided into the pN1, pN2 and pN3 categories of the AJCC/UICC classification, survival differed significantly (p = 0.00001). When both classifications were combined in a multivariate analysis the pN category of the AJCC/UICC classification was found to be the most significant independent prognostic factor (p = 0.0001). CONCLUSION: Classification of lymph node status by number of nodes (AJCC/UICC) rather than anatomical site (Japanese) gives a more accurate prognosis.