Urachal adenocarcinoma: A case report and review of the literature.

The urachus is a canal between the allantois and the early fetal bladder. Urachal carcinoma is a rare and aggressive type of bladder cancer. This cancer usually presents at an advanced stage. We report a 70-year-old patient with malignant transformation of urachal cyst several years later. The patient was treated with partial cystectomy and adjuvant radiotherapy. A review of the published literature is also presented.

Outcomes of patients with anal cancer treated with volumetric-modulated arc therapy or intensity-modulated radiotherapy and concurrent chemotherapy.

AIMS: To evaluate the results of chemoradiation with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) for the treatment of anal canal cancer patients at three institutions that had advanced devices. MATERIALS AND METHODS: A retrospective analysis was performed for patients treated with 5-fluorouracil and mitomycin-based chemotherapy and IMRT or VMAT for anal cancer from 2011 to 2013. Complete response (CR) rates, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and toxicities were investigated. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, Version 3.0. RESULTS: Fifteen patients were included in the analysis. The majority of patients had T2 (53.3%) and N0 (40%) disease according to the staging system that was developed by the American Joint Committee on Cancer. CR was observed in 14 patients (93%), and the median follow-up was 26 months (13-42 months). The 3-year CFS, DFS, and OS were 86%, 86%, and 88%, respectively. Acute Grade 3 toxicities were observed as 6% of hematological, 26% of gastrointestinal, and 26% of dermatological. CONCLUSION: Early results confirm that IMRT or VMAT for anal cancer treatment reduces acute toxicities while maintaining high control rates.

Evaluation of the relationship between serum ghrelin levels and cancer cachexia in patients with locally advanced nonsmall-cell lung cancer treated with chemoradiotherapy.

BACKGROUND: Ghrelin plays a role in mechanisms related to cancer progression - including cell proliferation, invasion and migration, and resistance to apoptosis in the cell lines from several cancers. We investigated the role of ghrelin levels in cancer cachexia-anorexia in patients with locally advanced nonsmall-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). MATERIALS AND METHODS: This study involved 84 NSCLC patients who had received concomitant CRT. Blood ghrelin levels were compared before and 3 months after CRT. Meanwhile, changes in body weight of the patients were also investigated with changes in ghrelin levels before and after CRT. RESULTS: Ghrelin levels were significantly decreased in line with changes in patients' weights in patients receiving CRT (P < 0.001). Serum albumin levels and inflammatory-nutritional index were significantly decreased after radiotherapy (RT) (3.01 ± 0.40 g/dL, 0.38 ± 0.20) when compared with its baseline levels (3.40 ± 0.55 g/dL,P < 0.001; 0.86 ± 0.71,P < 0.001, respectively). Serum C-reactive protein levels were significantly increased after CRT (7.49 ± 6.53 mg/L) when compared with its baseline levels (9.54 ± 3.80 mg/L,P = 0.038). After RT, ghrelin levels in patients were positively correlated with body mass index (r = 0.830,P < 0.001) and albumin (r = 0.758,P < 0.001). CONCLUSION: Ghrelin may play a role in the pathogenesis of weight loss in NSCLC patients. Ghrelin seems to be implicated in cancer-related weight loss. Ghrelin, cancer, and RT all together have a role in tumor-related anorexia-cachexia in patients with NSCLC. Results of this study need further evaluation as regards to its potential role as an adjuvant diagnostic or prognostic marker.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

AIM: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS: A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS: In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION: Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study.

AIM: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study. MATERIALS AND METHODS: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported. RESULTS: The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002). CONCLUSION: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.

LGALS3 and AXIN1 gene variants playing role in the Wnt/ ß-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer.

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ ß-catenin pathway by binding to ß-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the ß-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ ß-catenin pathway in the pathogenesis of colorectal cancer.

Does early PET/CT assesment of response to chemotherapy predicts survival in patients with advanced stage non-small-cell lung cancer?

The aim of this study is to determine the prognostic role and the timing of metabolic response to chemotherapy, based on F-fluorodeoxyglucose positron emission tomography (F-FDG-PET), in patients with metastatic non-small-cell lung cancer (NSCLC). The study included 55 patients with metastatic NSCLC that were analyzed in terms of prognostic factors and survival. F-FDG-PET/CT findings were evaluated in patients separated into 3 groups, before and after 1st, 2nd, 3rd cycle of the first line chemotherapy. Metabolic response was assessed according to PET Response Criteria in Solid Tumors (PERCIST 1.0). Among the 55 patients, 34 (62%) died, and 21 (38%) remained alive during a mean follow-up of 13.5 months. Median overall survival (OS) was 11.69 months (range 2-26.80 months) and median progression-free survival (PFS) was 6.27 months (range 1.37-20.43 months). Univariate analysis showed that the only favorable prognostic factor for OS in all the patients was the achievement of metabolic response. Metabolic response according to PERCIST, and weight lose ≤ 5% were also independent favorable prognostic factors predictive of survival in all patients based on multivariet analysis (metabolic response: P=0.002, OR; 1.90, 95% CI 1.26-2.89, and weight lose ≤5%: P=0.022, OR; 2.24, 95% CI 1.12-4.47). Median OS in all patients with partial response (PR)-according to the PERCIST 1.0- was significantly longer than in those with progressive disease (PD) (16.36 months vs 8.14 months, P=0.008). Median OS in the patients with PR was significantly longer than in those with PD based on PET/CT performed after 2nd and 3rd cycles of chemotherapy (18.35 months vs 7.54 months, P=0.012 and 18.04 months vs 7.43 months, P<0.001, respectively), whereas, median OS did not differ significantly between patients with PR and those with PD based on PET/CT performed after the 1st cycle of chemotherapy (8.01 months vs 5.08 months, P=0.290). Metabolic response according to PERCIST and weight loss are independent factors predictive of OS. PET/CT performed after second cycle of chemotherapy may be the earliest predictor of treatment response in patients with advanced stage NSCLC.

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study.

PURPOSE: The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. METHODS: Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m(2) per day; 60% dose at 8:00 AM and 40% dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity. RESULTS: In 17 patients (20%), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5%), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5%) subjects, and grade I or II cystitis in six (6.9%). Only three patients (3.3%) developed hand and foot syndrome (both grade I-II). There were no grade IV toxicities. CONCLUSIONS: Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.

Bone health in breast cancer patients: a comprehensive statement by CECOG/SAKK Intergroup.

Bone is the most common site of distant metastases in breast cancer that can cause severe and debilitating skeletal related events (SRE) including hypercalcemia of malignancy, pathologic fracture, spinal cord compression and the need for palliative radiation therapy or surgery to the bone. SRE are associated with substantial pain and morbidity leading to frequent hospitalization, impaired quality of life and poor prognosis. The past 25 years of research on the pathophysiology of bone metastases led to the development of highly effective treatment options to delay or prevent osseous metastases and SRE. Management of bone metastases has become an integral part of cancer treatment requiring expertise of multidisciplinary teams of medical and radiation oncologists, surgeons and radiologists in order to find an optimal treatment for each individual patient. A group of international breast cancer experts attended a Skeletal Care Academy Meeting in November 2012 in Istanbul and discussed current preventive measures and treatment options of SRE, which are summarized in this evidence-based consensus for qualified decision- making in clinical practice.

Comparison of two different adjuvant treatment modalities for pN3 gastric cancer patients after D2 lymph node dissection: can we avoid radiotherapy in a subgroup of patients?

Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer patients in the USA. However, in countries where D2 lymph node dissection is performed, the effect of radiotherapy on locoregional recurrence is controversial. The aim of this study is to compare the outcomes in pN3 gastric cancer patients following two adjuvant treatment modalities: chemotherapy (CT) and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer patients who underwent D2 lymph node dissection and had pTanyN3M0 stage (according to AJCC 6th edition) were identified. Fifty-three patients were treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during radiotherapy. For the CT arm, treatment protocols consisted of combination therapies involving FU and cisplatin as the backbone. Median overall survival (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15-37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT, respectively). Locoregional recurrence rates were also similar (p = 0.63). Only metastatic/dissected lymph node ratio (≥0.75) was identified as a prognostic factor in both univariate and multivariate analyses for DFS. Comparison of CT versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did not reveal any statistically significant difference in survival rates and locoregional recurrence.

Can diffusion-weighted MRI determine complete responders after neoadjuvant chemoradiation for locally advanced rectal cancer?

PURPOSE: We aimed to prospectively determine if analyzing pre- and post-chemoradiotheraphy (CRT) changes in the signal intensity (SI) and apperent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI) can accurately predict complete responders for locally advanced rectal cancer. MATERIALS AND METHODS: Thirty patients (mean age, 54.3 years) with locally advanced rectal cancer who underwent neoadjuvant CRT and subsequent surgery were included in this study. All patients were evaluated pre- and post-CRT by standardized turbo spin echo and DW-MRI. Pre- and post-CRT tumor and normal rectal wall SI (which were gradually scored as very high, high, intermediate, low, and no signal) and ADC values were recorded. RESULTS: Tumor SIs were decreased in all of the patients that had a therapy response. However, complete tumor SI loss was only seen in two (22.2%) of nine patients with a pathological complete response, while it regressed to low and/or intermediate SI levels in the remaining seven patients (77.8%). Post-CRT ADC values of rectal tumors were significantly higher from the preCRT ADC values (P < 0.0001; Z=-9.39). However, post-CRT ADC values from the complete and partial/no response patient groups were not significantly different (P = 0.071; Z=-1.99). CONCLUSION: In re-staging of rectal tumors by DW-MRI, an increase in ADC values and decrease in SIs can predict therapy response but cannot unequivocally determine a complete response.