Abstract Doxorubicin (DOX) is a first choice cytostatic drug in treatment of many cancers but among its side effects is cardiac toxicity. Stearidonic omega-3 fatty acid (SDA) has cardiac protective qualities and, therefore, we investigated the combinatory effects of DOX and SDA on proliferation/viability in the human prostate cancer (PCa) cell lines LNCaP, PC3, and DU145 as well as possible modulatory effects on expression of androgen receptor (AR), peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear transcription factors implicated in tumorigenesis. The median inhibitory effects (IC50) of SDA were 601, 116, 145 µM and that of DOX were 802, 761, 363 nM in LNCaP, PC3 and DU145, respectively. Equipotent combinations of DOX and SDA based on 2-fold dilutions and constant combination ratios derived from the above IC50 values suggested anticancer synergism with a combination index (CI) of less than 1 as determined using the Chou-Talalay method based on the median-effect equation and the mass action law. Stearidonic acid strongly inhibited TNFα-activated NF-κB in stably transduced LNCaP cells. We used immunocytochemistry, real-time PCR, western blotting, and transactivation assays to demonstrate inhibition of agonist-activated AR and PPARγ expression following treatment with DOX and SDA singly or in combination. This study provides proof-of-concept for using DOX and SDA in combination to reduce dose and toxicity of DOX in PCa clinical translation studies.
Keywords: stearidonic acid; doxorubicin; drug combination; peroxisome proliferator-activated receptor; nuclear factor kappa-light-chain-enhancer; antitumor activity; human prostate cancer

Abstract Background: Adjuvant radiotherapy reduces nodal recurrence in metastatic melanoma. The purpose of this study was to examine the effects of adjuvant radiotherapy on in-field nodal control of melanoma metastatic to axillary and inguinal lymph nodes. Methods: The medical records of patients who received adjuvant radiotherapy from January 1, 2003, through December 31, 2011, at Mayo Clinic were reviewed. Results: In the 20 patients identified, the rates of 2-year overall survival, nodal control, and freedom from distant metastases were 53%, 54%, and 44%, respectively. Intensity-modulated radiotherapy was used in 15 patients (75%) and 3-dimensional conformal radiotherapy in 5 (25%). Disease progression was documented in 13 patients, with a total of 10 distant metastases and 6 in-field nodal recurrences. Treatment complications occurred in 14 patients: lymphedema, 9; lymphedema and fibrosis, 1; lymphedema and wound dehiscence, 1; wound dehiscence, 1; lymphedema and seroma, 1; and lymphedema, seroma, and fibrosis, 1. Conclusion: Patients with axillary and inguinal nodal metastases from melanoma have poor overall survival. Surgery and adjuvant radiotherapy provided a 54% nodal control rate. No plexopathy or grade 3 lymphedema complications were seen; however, 20% developed wound dehiscence.
Keywords: adjuvant radiotherapy; axillary; inguinal; lymph node; melanoma; metastasis

Abstract Aim: To analyze our experience confronting meso-esophagogastric resection (transhiatally extended total gastrectomy en-bloc with its inviolate primitive dorsal and ventral mesenterium) to less radical planes of surgery (intra-mesoesophagogastric and muscularis propria planes), in the multimodal management of junctional Siewert II/III resectable gastric cancer. Methods: 138 patients with stage I-III/C type II-III Siewert junctional cancers were enrolled. Proximal and distal marginal clearance, closest meso-esophageal resection margin (CRM), volume in mm³ of meso-esophageal tissue around the tumor, R0 resections rate, number of lymph nodes harvested and five years overall and disease-free survival were recorded for each plane of surgery. Results: Mortality and morbidity were 3.6% and 22.4% respectively; operative length was 235 ± 23 min.; mean blood loss was 195 ± 53cc. Mean meso-esophageal tissue volume including tumor was 35,157 mm³ for meso-esophagogastric resections, 25,397 mm³ for intra-mesoesophagogastric resections and 20,531 mm³ for “muscularis propria” resections, all statistically significant (p < 0.05). Mean follow-up was 40.3 months. Five years overall survival was 52.2% for meso-esophagogastric resection, 45% for intra-mesoesophagogastric and 35.2% for muscularis propria resections, all statistically significant; the difference was particularly enhanced in stage II-IIIA/B (56.2%, 47.8% and 30% for meso-esophagogastric, intra-meso-esophagogastric and muscularis propria planes respectively). On multivariate analysis, meso-esophagogastric plane of resection, pCR after neo-adjuvant chemo-radiation, R0, CRM > 1mm and pN0 were associated with increased recurrence-free survival. Conclusions: When compared to less extensive planes of surgery, transhiatally extended total meso-esophagogastrectomy confers a survival advantage in the intermediate stages of Siewert type II-III junctional gastric cancer, increasing R0 resection rate, decreasing CRM < 1mm and enhancing lymph node harvesting, with consequent impact on loco-regional control and survival; differently, in the extreme stages (I and IIIC N + patients), total meso-esophagogastrectomy is ineffective in altering the standard oncologic outcome. In our experience, total meso-esophagogastrectomy proved to be safe and oncologically effective, especially in stage II-IIIA/B, representing a pivotal part of multimodal management of type II/III EGJ cancers.
Keywords: meso-esophagectomy; meso-gastrectomy; Siewert II/III esophagogastric junctional cancer; safety; long term oncologic outcome

Abstract Aims: To identify changing trends in gastrointestinal cancer incidence in Indonesia according to age, gender, histopathology, and cancer location. Methods: We examined retrospectively the demography, cancer location, and pathological characteristics of 295 consecutive gastrointestinal cancer patients admitted to Cipto Mangunkusumo National General Hospital in 2002–2006. We compared these data with data from 343 gastrointestinal cancer patients admitted in 2007–2011. The data were analyzed by chi-square, analysis of variance, Kolmogorov–Smirnov, and Mann–Whitney U tests using SPSS 21.0. Results: The most prevalent gastrointestinal cancers in 2002–2006 and 2007–2011 were colorectal cancer (76.3% and 71.4%), followed by gastric cancer (15.6% and 14.9%), esophageal cancer (7.4% and 7.6%), and duodenal cancer (0.7% and 6.1%).There was an increase in esophageal adenocarcinoma prevalence from 36.4% to 69.2% (p = 0.023). The mean age at diagnosis of esophageal cancer decreased from 53.02 ± 13.12) to 50.43 ± 11.93) years (p = 0.031). The percentage of patients with gastric cancer aged 30–60 years increased from 60.9% to 82.4% (p = 0.018) and the percentage of patients aged > 60 years decreased from 34.8% to 13.7% (p = 0.015). In the histopathological analysis of gastric cancer, the prevalence of adenocarcinoma increased from 58.7% to 78.4% (p = 0.036), whereas the prevalence of signet ring cell carcinoma decreased from 21.7% to 5.9% (p = 0.022). The prevalence of gastric cancer lesions extending to >1 location increased from 2.2% to 27.5% (p = 0.001).The frequency of duodenal cancer among women increased non significantly from 0% to 52.4% (p = 0.261). The demography, histopathology, and location of colorectal cancers did not change between the two periods. Conclusions: Our study shows some changing trends in gastrointestinal malignancy in Indonesia in terms of demography, histopathology, and the location of cancers from 2002–2006 to 2007–2011.
Keywords: changing trends; gastrointestinal cancer; esophageal cancer; gastric cancer; duodenal cancer; colorectal cancer; Indonesia