The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)

Neoadjuvant Chemoradiation Herapy for Soft Tissue Sarcomas of the Extremities

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients

Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor

Background: Whether the TNM staging system is applicable after neoadjuvant chemoradiation in esophageal cancer is controversial. The aim of this study was to evaluate the prognostic value of histopathological regression of the primary tumor in postchemoradiated patients. Materials and Methods: The pretherapeutic and pathological ypTNM stages of patients who have had neoadjuvant chemoradiation followed by esophagectomy were analyzed. The percentage of residual viable cells of the primary tumor (ypV) and other clinicopathological factors were tested for their prognostic value. Results: Of 175 recruited patients, 55 (31.4%) achieved pathological complete response. The median survival of these 55 patients was significantly longer than those with other disease stages (124.8 vs 21.1 months) (P <.001). Gender, ypT, ypN, ypTNM, and ypV stage were significant prognostic factors in univariate analysis. In patients without nodal metastases, the median survival in patients with residual viable cells in the primary tumor (ypV?) was 24.6 months, compared with that of 124.8 months in those with no viable cells (ypV0) (P =.043). In those who had nodal metastases, the median survival of patients with ypV0 and ypV? were 21.2 months and 17.4 months respectively (P =.37). Cox regression analysis showed that male gender, high percentage of residual viable cells (ypV), and positive nodal status (ypN1) were independent predictors of poor prognosis. Conclusions: In patients who underwent neoadjuvant chemoradiation therapy, histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor in addition to nodal status and gender. © The Author(s) 2010.published_or_final_versionSpringer Open Choice, 01 Dec 201

Intraoperative Transfusion is Independently Associated with a Worse Prognosis in Resected Pancreatic Cancer-a Retrospective Cohort Analysis

BACKGROUNDS: Investigate whether intraoperative transfusion is a negative prognostic factor for oncologic outcomes of resected pancreatic cancer. METHODS: From June 2004 to January 2014, the medical records of 305 patients were retrospectively reviewed, who underwent pancreatoduodenectomy, pylorus preserving pancreatoduodenectomy, total pancreatectomy, distal pancreatectomy for pancreatic cancer. Patients diagnosed with metastatic disease (n = 3) and locally advanced diseases (n = 15) were excluded during the analysis, and total of 287 patients were analyzed. RESULTS: The recurrence and disease-specific survival rates of the patients who received intraoperative transfusion showed poorer survival outcomes compared to those who did not (P = 0.031, P = 0.010). Through multivariate analysis, T status (HR (hazard ratio) = 2.04, [95% CI (confidence interval): 1.13-3.68], P = 0.018), N status (HR = 1.46 [95% CI: 1.00-2.12], P = 0.045), adjuvant chemotherapy (HR = 0.51, [95% CI: 0.35-0.75], P = 0.001), intraoperative transfusion (HR = 1.94 [95% CI: 1.23-3.07], P = 0.004) were independent prognostic factors of disease-specific survival after surgery. As well, adjuvant chemotherapy (HR = 0.67, [95% CI: 0.46-0.97], P = 0.035) was independently associated with tumor recurrence. Estimated blood loss was one of the most powerful factors associated with intraoperative transfusion (P < 0.001). CONCLUSIONS: Intraoperative transfusion can be considered as an independent prognostic factor of resected pancreatic cancer. As well, it can be avoided by following strict transfusion policy and using advanced surgical techniques to minimize bleeding during surgery.ope

Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer.

Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC

Predicting rectal cancer T stage using circumferential tumor extent determined by computed tomography colonography

SummaryBackground and aimPatients with stage T3 or T4 rectal cancer are candidates for neoadjuvant chemoradiation therapy. The aim of this study is to clarify the usefulness of circumferential tumor extent determined by computed tomography (CT) colonography in differentiating T3 or T4 from T1 or T2 rectal cancer.MethodsSeventy consecutive rectal cancer patients who underwent curative-intent surgery were enrolled in this study. All patients underwent colonoscopy and CT colonography on the same day. The circumferential tumor extent was estimated in 10% increments. The pathological T stage was used as the reference.ResultsThe median circumferential tumor extent evaluated by colonoscopy for T1 (n = 6), T2 (n = 21), and T3/T4 (n = 43) were 10%, 30%, and 80%, respectively (T1/T2 vs. T3/T4, p < 0.0001). The median circumferential tumor extent evaluated by CT colonography for T1, T2, and T3/T4 is 10%, 30%, and 70%, respectively (T1/T2 vs. T3/T4, p < 0.0001). The correlation coefficient between colonoscopy and CT colonography was very high (0.94). By defining a circumferential tumor extent ≥50% by CT colonography as the criterion for stage T3 or T4, the sensitivity, specificity, positive predictive value and accuracy were 72%, 88%, 91%, and 79%, respectively.ConclusionCircumferential tumor extent ≥50% determined by CT colonography is a simple and potentially useful marker to identify candidates for neoadjuvant chemoradiation therapy

Transanal endoscopic microsurgery: what indications in 2013?

Thanks to major advances in the field of surgical techniques and neoadjuvant chemoradiation therapy, along with more accurate pre-operative staging tools and the widespread introduction of population-based screening programs, treatment of rectal cancer has been evolving over the past few decades, moving towards a more tailored approach. This has brought a shift in the treatment algorithm of benign rectal lesions and selected early rectal cancers, for which today transanal endoscopic microsurgery (TEM) is accepted as an effective alternative to abdominal surgery. In 2013, topics of controversy are the role of TEM in the treatment of more advanced rectal cancers, in cases of complete pathological response after chemoradiation therapy and the role of TEM as a platform for single-port surgery and NOTES. This article reviews the current indications for TEM and the future perspectives of this approach in the treatment of rectal tumors